publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/192430

5958 lines
658 KiB
Text
Raw Permalink Blame History

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
<head>
<!--
################################# CRAWLER WARNING #################################
- The terms of service and the robots.txt file disallows crawling of this site,
please see https://omim.org/help/agreement for more information.
- A number of data files are available for download at https://omim.org/downloads.
- We have an API which you can learn about at https://omim.org/help/api and register
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
- You should feel free to contact us at https://omim.org/contact to figure out the best
approach to getting the data you need for your work.
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
DISTRIBUTED CRAWLS OF THIS SITE.
################################# CRAWLER WARNING #################################
-->
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
<meta http-equiv="cache-control" content="no-cache" />
<meta http-equiv="pragma" content="no-cache" />
<meta name="robots" content="index, follow" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
contain copious links to other genetics resources." />
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
<meta name="theme-color" content="#333333" />
<link rel="icon" href="/static/omim/favicon.png" />
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
<link rel="manifest" href="/static/omim/manifest.json" />
<script id='mimBrowserCapability'>
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
</script>
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
<link rel="preconnect" href="https://www.googletagmanager.com" />
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag(){window.dataLayer.push(arguments);}
gtag("js", new Date());
gtag("config", "G-HMPSQC23JJ");
</script>
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
<div id="mimBootstrapDeviceSize">
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
</div>
<title>
Entry
- #192430 - VELOCARDIOFACIAL SYNDROME; VCFS
- OMIM
</title>
</head>
<body>
<div id="mimBody">
<div id="mimHeader" class="hidden-print">
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
<div class="container-fluid">
<!-- Brand and toggle get grouped for better mobile display -->
<div class="navbar-header">
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
<span class="sr-only"> Toggle navigation </span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
</button>
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
</div>
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
<ul class="nav navbar-nav">
<li>
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
</li>
<li class="dropdown">
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
<li>
<a href="/statistics/update"> Update List </a>
</li>
<li>
<a href="/statistics/entry"> Entry Statistics </a>
</li>
<li>
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
</li>
<li>
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
<li>
<a href="/downloads/"> Register for Downloads </a>
</li>
<li>
<a href="/api"> Register for API Access </a>
</li>
</ul>
</li>
<li>
<a href="/contact?mimNumber=192430"><span class="mim-navbar-menu-font"> Contact Us </span></a>
</li>
<li>
<a href="/mimmatch/">
<span class="mim-navbar-menu-font">
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
MIMmatch
</span>
</span>
</a>
</li>
<li class="dropdown">
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
<li>
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
</li>
<li>
<a href="/donors"> Donors </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
<li>
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/search"> Search Help </a>
</li>
<li>
<a href="/help/linking"> Linking Help </a>
</li>
<li>
<a href="/help/api"> API Help </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/external"> External Links </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/agreement"> Use Agreement </a>
</li>
<li>
<a href="/help/copyright"> Copyright </a>
</li>
</ul>
</li>
<li>
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
</li>
</ul>
</div>
</div>
</nav>
</div>
<div id="mimSearch" class="hidden-print">
<div class="container">
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
<input type="hidden" id="mimSearchStart" name="start" value="1" />
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
<div class="row">
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
<div class="form-group">
<div class="input-group">
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
<div class="input-group-btn">
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
<ul class="dropdown-menu dropdown-menu-right">
<li class="dropdown-header">
Advanced Search
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/entry"> OMIM </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/geneMap"> Gene Map </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/history"> Search History </a>
</li>
</ul>
</div>
</div>
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
</div>
</div>
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
<span class="small">
</span>
</div>
</div>
</form>
<div class="row">
<p />
</div>
</div>
</div>
<!-- <div id="mimSearch"> -->
<div id="mimContent">
<div class="container hidden-print">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<div id="mimAlertBanner">
</div>
</div>
</div>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
<div id="mimFloatingTocMenu" class="small" role="navigation">
<p>
<span class="h4">#192430</span>
<br />
<strong>Table of Contents</strong>
</p>
<nav>
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
<li role="presentation">
<a href="#title"><strong>Title</strong></a>
</li>
<li role="presentation">
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
</li>
<li role="presentation">
<a href="/clinicalSynopsis/192430"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#cytogenetics">Cytogenetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#heterogeneity">Heterogeneity</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</a>
</li>
<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">External Links</div>
</div>
</a>
</h4>
</div>
</div>
<div id="mimExternalLinksFold" class="collapse in">
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=VELOCARDIOFACIAL SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://decipher.sanger.ac.uk/syndrome/16" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=126&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1523/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/22q112-deletion-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=192430[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=567" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/1481adb9-16ac-4f64-a87b-30c6fa2eff3c/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:12583" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/192430" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:12583" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:192430" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ICD10CM:</strong> Q93.81<br />
<strong>ICD9CM:</strong> 758.32<br />
<strong>ORPHA:</strong> 567<br />
<strong>DO:</strong> 12583<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
192430
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
VELOCARDIOFACIAL SYNDROME; VCFS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CHROMOSOME 22q11.2 DELETION SYNDROME<br />
VCF SYNDROME<br />
SHPRINTZEN VCF SYNDROME
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/48?start=-3&limit=10&highlight=48">
22q11.21
</a>
</span>
</td>
<td>
<span class="mim-font">
Velocardiofacial syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/192430"> 192430 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
TBX1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602054"> 602054 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/192430" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/192430" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/192430" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Long <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255511005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255511005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1706317&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1706317</a>, <a href="https://bioportal.bioontology.org/search?q=C0205166&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0205166</a>]</span><br /> -
Pierre Robin syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4602007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4602007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q87.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q87.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0031900&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0031900</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000201" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000201</a>]</span><br /> -
Retrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109515000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109515000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035353</a>, <a href="https://bioportal.bioontology.org/search?q=C3494422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3494422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Retrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Minor auricular anomalies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860476&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860476</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow palpebral fissures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/370116005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">370116005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675021</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045025</a>]</span><br /> -
Small optic discs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/423389004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">423389004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1828214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1828214</a>]</span><br /> -
Tortuous retinal vessels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860475&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860475</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012841" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012841</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012841" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012841</a>]</span><br /> -
Posterior embryotoxon <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/392437005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">392437005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0546967&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0546967</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000627</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000627</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Square nasal root <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860477&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860477</a>]</span><br /> -
Decreased nasopharyngeal lymphoid tissue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860478&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860478</a>]</span><br /> -
Prominent tubular nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860479</a>]</span><br /> -
Hypoplastic nasal alae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000430" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000430</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000430" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000430</a>]</span><br /> -
Bulbous nasal tip <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855751&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855751</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000414</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000414</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=50ff569bd76b9a6cd5dba7aabce89564" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nose,Bulbous-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=50ff569bd76b9a6cd5dba7aabce89564&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cleft palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br /> -
Velopharyngeal insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/232416001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">232416001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229726002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229726002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042454</a>, <a href="https://bioportal.bioontology.org/search?q=C0454634&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0454634</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000220</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000220" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000220</a>]</span><br /> -
Small open mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860480</a>]</span><br /> -
Pharyngeal hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860481</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Congenital abnormality in 85% <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860486&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860486</a>]</span><br /> -
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
Tetralogy of Fallot <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86299006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86299006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0039685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039685</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001636" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001636</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001636" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001636</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Right aortic arch <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/244229003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">244229003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111321007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.47" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.47</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035615</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012020</a>]</span><br /> -
Aberrant left subclavian <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860487&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860487</a>]</span><br /> -
Internal carotid artery abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860488&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860488</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:3000062" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:3000062</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Lung </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Primary pulmonary dysgenesis, unilateral (reported in 2 unrelated patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4021592&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4021592</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006549" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006549</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006549" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006549</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Inguinal hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396232000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396232000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K40.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">550</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019294</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span><br /> -
Umbilical hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396347007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396347007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/553.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">553.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019322</a>, <a href="https://bioportal.bioontology.org/search?q=C0041636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Slender hands and digits <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860483&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860483</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Learning disability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1855002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1855002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/408468001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">408468001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F81.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F81.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1321592&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1321592</a>, <a href="https://bioportal.bioontology.org/search?q=C0751265&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751265</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001328" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001328</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Behavioral Psychiatric Manifestations </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Blunt or inappropriate affect <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860473&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860473</a>]</span><br /> -
Psychotic illness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860474&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860474</a>]</span><br /> -
Paranoia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/191667009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">191667009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1456784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1456784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011999</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011999" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011999</a>]</span><br /> -
Autistic features <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846135&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846135</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000729</a>]</span><br /> -
Aggression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61372001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61372001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001807&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001807</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006919</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000718</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000718</a>]</span><br /> -
Mood swings <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18963009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18963009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R45.86" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R45.86</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085633&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085633</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000712</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000712</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> VOICE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Nasal voice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/289190003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">289190003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0566620&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0566620</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001611</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001611</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Neonatal hypocalcemia, rare <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860472</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Frequent infections T-lymphocyte dysfunction, rare <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860482&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860482</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Monosomy for 22q11 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860484</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Overlapping features of DiGeorge syndrome<br /> -
Incidence is estimated to be between 1 in 2,000 to 1 in 7,000 live births<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- A contiguous gene syndrome caused by deletion (1.5Mb - 3.0Mb) of 22q11.2<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because the velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS; <a href="/entry/188400">188400</a>) are caused by a 1.5- to 3.0-Mb hemizygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (<a href="/entry/602054">602054</a>) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the syndrome in most patients.</p><p><a href="#66" class="mim-tip-reference" title="Shprintzen, R. J., Goldberg, R. B., Young, D., Wolford, L. &lt;strong&gt;The velo-cardio-facial syndrome: a clinical and genetic analysis.&lt;/strong&gt; Pediatrics 67: 167-172, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7243439/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7243439&lt;/a&gt;]" pmid="7243439">Shprintzen et al. (1981)</a> reported on 39 patients with a syndrome characterized by the following frequent features: cleft palate, cardiac anomalies, typical facies, and learning disabilities. Less frequent features included microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, and inguinal hernia. The Pierre Robin syndrome was present in 4. The heart malformation was most often ventricular septal defect. In the group studied, mother and daughter were affected in 2 instances, mother and son in 1, and mother and both daughter and son in 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7243439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Fitch, N. &lt;strong&gt;Velo-cardio-facial syndrome and eye abnormality. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 15: 669 only, 1983."None>Fitch (1983)</a> found small optic discs with tortuous vessels in an affected 6-year-old girl, the offspring of first-cousin parents.</p><p><a href="#85" class="mim-tip-reference" title="Wraith, J. E., Super, M., Watson, G. H., Phillips, M. &lt;strong&gt;Velo-cardio-facial syndrome presenting as holoprosencephaly.&lt;/strong&gt; Clin. Genet. 27: 408-410, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3995791/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3995791&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1985.tb02284.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3995791">Wraith et al. (1985)</a> reported a male infant with holoprosencephaly and tetralogy of Fallot with death at 32 days. The mother had the same heart lesion, tetralogy of Fallot (totally corrected by surgery at age 12 years), and a large submucous cleft palate causing nasal voice. Her face was considered typical of VCF syndrome: prominent tubular nose, narrow palpebral fissures, and slightly retruded mandible. She was mildly retarded. Another child, female, may have been affected. The authors suggested that the association of tetralogy of Fallot and prosencephaly should prompt search for signs of VCF syndrome in relatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3995791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#68" class="mim-tip-reference" title="Shprintzen, R. J., Wang, F., Goldberg, R., Marion, R. &lt;strong&gt;The expanded velo-cardio-facial syndrome (VCF): additional features of the most common clefting syndrome. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A77, 1985."None>Shprintzen et al. (1985)</a> claimed that VCFS is the most frequent clefting syndrome, accounting for 8.1% of children with palatal clefts seen in their center. Learning disabilities characterized by difficulty with abstraction, reading comprehension, and mathematics is found in all cases as is a characteristic facial dysmorphia. Cardiac anomalies were found in 82%. Platybasia occurred in 85%. Ophthalmologic abnormalities, including tortuous retinal vessels, small optic discs, posterior embryotoxon, or bilateral cataracts, were observed in 70%. Neonatal hypocalcemia requiring treatment occurred in almost 13%. Small or absent lymphoid tissue was documented by nasopharyngoscopic examination in a great majority. Most patients had frequent infections, and T-lymphocyte dysfunction was found. Male-to-male transmission established autosomal dominant inheritance.</p><p>Marked tortuosity of the retinal vessels, as noted in earlier reports, was commented on by <a href="#3" class="mim-tip-reference" title="Beemer, F. A., de Nef, J. J. E. M., Delleman, J. W., Bleeker-Wagemakers, E. M., Shprintzen, R. J. &lt;strong&gt;Additional eye findings in a girl with the velo-cardio-facial syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 24: 541-542, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3089013/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3089013&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320240319&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3089013">Beemer et al. (1986)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3089013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#48" class="mim-tip-reference" title="Meinecke, P., Beemer, F. A., Schinzel, A., Kushnick, T. &lt;strong&gt;The velo-cardio-facial (Shprintzen) syndrome: clinical variability in eight patients.&lt;/strong&gt; Europ. J. Pediat. 145: 539-544, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3816857/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3816857&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02429059&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3816857">Meinecke et al. (1986)</a> reported 8 patients with the VCF syndrome; 3 cases were sporadic and 5 others occurred in 2 families. The authors concluded that the frequency of cardiovascular anomalies and cleft palate has been incorrectly estimated to be high, 98% and 82%, respectively, because patients have been ascertained in cardiac or cleft palate clinics. Their 8 patients were diagnosed mainly through their pattern of facial dysmorphism and only 2 and 4 of the 8, respectively, had clefts and heart defects. Furthermore, mental retardation, noted in all cases in previous publications, was not present in any of these 8 patients. They suspected that the rate of fresh mutations may not be as high as previously assumed because of mild expression in some family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3816857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#82" class="mim-tip-reference" title="Williams, M. A., Shprintzen, R. J., Rakoff, S. J. &lt;strong&gt;Adenoid hypoplasia in the velo-cardio-facial syndrome.&lt;/strong&gt; J. Craniofac. Genet. Dev. Biol. 7: 23-26, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3597719/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3597719&lt;/a&gt;]" pmid="3597719">Williams et al. (1987)</a> found evidence for congenital hypoplasia of the adenoids in over four-fifths of patients with the VCF syndrome. They suggested that this feature contributes to the hypernasal speech found in persons with this condition because normally velopharyngeal closure during speech is aided by the adenoids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3597719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Lipson, A. H., Yuille, D., Angel, M., Thompson, P. G., Vandervoord, J. G., Beckenham, E. J. &lt;strong&gt;Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognize.&lt;/strong&gt; J. Med. Genet. 28: 596-604, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1956057/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1956057&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.9.596&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1956057">Lipson et al. (1991)</a> reported on 38 cases including 2 familial cases. They emphasized the frequent delay in diagnosis and treatment for the hypernasal speech and velopharyngeal insufficiency. Overt cleft palate was present in 7 of the cases and submucous cleft in 15. Congenital heart disease was present in 16. Velopharyngeal insufficiency was present in all but one; pharyngoplasty was performed in all but 6 of the cases and results were good in all of these. <a href="#41" class="mim-tip-reference" title="Lipson, A. H., Yuille, D., Angel, M., Thompson, P. G., Vandervoord, J. G., Beckenham, E. J. &lt;strong&gt;Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognize.&lt;/strong&gt; J. Med. Genet. 28: 596-604, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1956057/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1956057&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.9.596&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1956057">Lipson et al. (1991)</a> published photographs illustrating the main facial features: almond-shaped palpebral fissures, deficient nasal alae, bulbous nasal tip in older children, myopathic facies, and small open mouth. Hypernasal speech was often the finding that brought the children to attention. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1956057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Goldberg, R., Motzkin, B., Marion, R., Scambler, P. J., Shprintzen, R. J. &lt;strong&gt;Velo-cardio-facial syndrome: a review of 120 patients.&lt;/strong&gt; Am. J. Med. Genet. 45: 313-319, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434617/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434617&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450307&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434617">Goldberg et al. (1993)</a> reviewed the full spectrum of the velocardiofacial syndrome on the basis of 120 patients. Learning disability, cleft palate, and pharyngeal hypotonia were present in 90% or more of the patients; cardiac anomalies in 82%; slender hands and digits in 63%; medial displacement of internal carotid arteries in 25%; umbilical hernia in 23%; and hypospadias in 10% of males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#53" class="mim-tip-reference" title="Nickel, R. E., Pillers, D.-A. M., Merkens, M., Magenis, R. E., Driscoll, D. A., Emanuel, B. S., Zonana, J. &lt;strong&gt;Velo-cardial-facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region.&lt;/strong&gt; Am. J. Med. Genet. 52: 445-449, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7747757/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7747757&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320520410&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7747757">Nickel et al. (1994)</a> reported 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of VCFS; both also had bifid uvula. The third child had DiGeorge sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7747757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#64" class="mim-tip-reference" title="Scire, G., Dallapiccola, B., Iannetti, P., Bonaiuto, F., Galasso, C., Mingarelli, R., Boscherini, B. &lt;strong&gt;Hypoparathyroidism as the major manifestation in two patients with 22q11 deletions.&lt;/strong&gt; Am. J. Med. Genet. 52: 478-482, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7747762/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7747762&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320520415&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7747762">Scire et al. (1994)</a> reported clinical features of 2 adolescent males illustrating that the main manifestation of 22q11 deletion can be chronic symptomatic hypocalcemia secondary to hypoparathyroidism, together with seizures and cerebral calcifications. The patients had no cardiac abnormality or T-cell deficiency and had no cleft palate, features that occur in the DiGeorge syndrome (<a href="/entry/188400">188400</a>) and VCFS. The patients did have facial features of VCFS, and one in particular had a hypernasal voice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7747762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#44" class="mim-tip-reference" title="Makita, Y., Masuno, M., Imaizumi, K., Tachibana, K., Kuroki, Y. &lt;strong&gt;Idiopathic hypoparathyroidism in two patients with 22q11 microdeletion. (Letter)&lt;/strong&gt; J. Med. Genet. 32: 669, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7473668/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7473668&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.8.669&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7473668">Makita et al. (1995)</a> reported 2 further cases of isolated hypoparathyroidism in whom they demonstrated a 22q11 deletion by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7473668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Kousseff, B. G. &lt;strong&gt;Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait.&lt;/strong&gt; Pediatrics 74: 395-398, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6472972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6472972&lt;/a&gt;]" pmid="6472972">Kousseff (1984)</a> described 3 sibs with a syndrome of sacral meningocele, conotruncal cardiac defects, unilateral renal agenesis (in 1 sib), low-set and posteriorly angulated ears, retrognathia, and short neck with low posterior hairline. <a href="#39" class="mim-tip-reference" title="Kousseff, B. G. &lt;strong&gt;Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait.&lt;/strong&gt; Pediatrics 74: 395-398, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6472972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6472972&lt;/a&gt;]" pmid="6472972">Kousseff (1984)</a> suggested autosomal recessive inheritance. <a href="#75" class="mim-tip-reference" title="Toriello, H. V., Sharda, J. K., Beaumont, E. J. &lt;strong&gt;Autosomal recessive syndrome of sacral and conotruncal developmental field defects (Kousseff syndrome).&lt;/strong&gt; Am. J. Med. Genet. 22: 357-360, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4050868/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4050868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320220220&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4050868">Toriello et al. (1985)</a> reported a similar, isolated case and designated the disorder Kousseff syndrome. <a href="#20" class="mim-tip-reference" title="Forrester, S., Kovach, M. J., Smith, R. E., Rimer, L., Wesson, M. &lt;strong&gt;Kousseff syndrome caused by deletion of chromosome 22q11-13.&lt;/strong&gt; Am. J. Med. Genet. 112: 338-342, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12376934/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12376934&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.10625&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12376934">Forrester et al. (2002)</a> restudied the family reported by <a href="#39" class="mim-tip-reference" title="Kousseff, B. G. &lt;strong&gt;Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait.&lt;/strong&gt; Pediatrics 74: 395-398, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6472972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6472972&lt;/a&gt;]" pmid="6472972">Kousseff (1984)</a> and identified a 22q11-q13 deletion in the proband, his deceased brother, and his father. The proband had spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velocardiofacial syndrome, including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. His brother had died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and his sister had died at 22 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6472972+12376934+4050868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Maclean, K., Field, M. J., Colley, A. S., Mowat, D. R., Sparrow, D. B., Dunwoodie, S. L., Kirk, E. P. E. &lt;strong&gt;Kousseff syndrome: a causally heterogeneous disorder.&lt;/strong&gt; Am. J. Med. Genet. 124A: 307-312, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14708106/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14708106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20418&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14708106">Maclean et al. (2004)</a> reported 2 patients with Kousseff syndrome, 1 with a 22q11.2 deletion and the other without. The first was a 4-year-old girl with a sacral myelomeningocele, tetralogy of Fallot, microcephaly, hydrocephalus, hypoplasia of the corpus callosum, and moderate developmental delay, who had a normal chromosome 22q11.2 FISH test and did not exhibit the facial phenotype of VCFS. The second patient, a male infant who died at 10 days of age, had a large sacral myelomeningocele, hydrocephalus, Arnold-Chiari malformation, atrial septal defect, conoventricular ventricular septal defect, type B interrupted aortic arch, hypocalcemia, and suspected duodenal stenosis; FISH testing revealed a 22q11.2 microdeletion. <a href="#43" class="mim-tip-reference" title="Maclean, K., Field, M. J., Colley, A. S., Mowat, D. R., Sparrow, D. B., Dunwoodie, S. L., Kirk, E. P. E. &lt;strong&gt;Kousseff syndrome: a causally heterogeneous disorder.&lt;/strong&gt; Am. J. Med. Genet. 124A: 307-312, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14708106/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14708106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20418&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14708106">Maclean et al. (2004)</a> concluded that Kousseff syndrome is a distinct clinical entity that is genetically heterogeneous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14708106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Lynch, D. R., McDonald-McGinn, D. M., Zackai, E. H., Emanuel, B. S., Driscoll, D. A., Whitaker, L. A., Fischbeck, K. H. &lt;strong&gt;Cerebellar atrophy in a patient with velocardiofacial syndrome.&lt;/strong&gt; J. Med. Genet. 32: 561-563, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7562973/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7562973&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.7.561&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7562973">Lynch et al. (1995)</a> reported the case of a 34-year-old man who presented for neurologic evaluation for cerebellar atrophy of unknown etiology. By history, he had had neonatal hypocalcemia, an atrial septal defect, and a corrected cleft palate. Physical examination showed the characteristic facies of velocardiofacial syndrome, as well as dysmetria and dysdiadochokinesia consistent with cerebellar degeneration. An MRI scan of his head performed by the authors showed vermian and hemispheric cerebellar atrophy, calcification of the basal ganglia, a small brainstem without focal loss of volume, and multiple white matter lucencies on T2-weighted images. The white matter lesions were suggestive of axonal loss, ischemia, or demyelination. Molecular cytogenetic studies showed a deletion of 22q11.2, del(22)(q11.21-q11.23). This case represented the first report of the association of a neurodegenerative disorder with velocardiofacial syndrome or DiGeorge syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7562973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#58" class="mim-tip-reference" title="Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others. &lt;strong&gt;Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.&lt;/strong&gt; J. Med. Genet. 34: 798-804, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9350810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9350810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.10.798&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9350810">Ryan et al. (1997)</a> reported a European collaborative study of 558 patients with deletions of 22q11. In 204 of the 285 patients for whom parental deletion status was available, neither parent had the deletion. Of the 81 inherited deletions, the sex of the parent with the deletion was known in 79 cases, with 61 maternal and 18 paternal deletions. Growth data were available for 131 of 158 patients whose heights and/or weights were less than the 50th centile; 57 of 158 were below the 3rd centile for either height or weight. Forty-four patients had died, and of the 29 for whom age of death was available, 16 had died within 1 month and 25 within 6 months as a consequence of congenital heart disease. There was 1 death from severe immune deficiency. A total of 107 of 338 cases were developmentally normal, although 37 of these had speech delay. Of 231 patients with abnormal development, 102 had mild delay and 60 had either moderate or severe learning difficulties. Twenty-two of 252 children in the study had behavioral or psychiatric problems, including 2 with episodes of psychosis; 11 of 61 adults had a psychiatric disorder, 4 of whom had had at least 1 episode of psychosis. Cardiac studies were recorded in 545 patients, of whom 409 had significant cardiac pathology, most commonly tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, pulmonary atresia/ventricular septal defect, and truncus arteriosus. A total of 242 of 496 patients had otolaryngeal abnormalities, with 72 having either an overt cleft palate or submucous cleft; 161 patients had velopharyngeal insufficiency without clefting. Of 159 patients in whom data on hearing were available, 52 had abnormal hearing, with data on the type of hearing loss available in only 17, in all of whom this was conductive in type. A total of 49 of 136 patients had renal abnormalities, with absent, dysplastic, or multicystic kidneys in 23, obstructive abnormalities in 14, and vesicoureteric reflux in 6. A total of 203 of 340 had recorded hypocalcemia; 108 of this group had a history of seizures, and 42 of these had had seizures secondary to hypocalcemia. Most hypocalcemia was reported in the neonatal period, but 1 patient presented at 18 years of age. Laboratory and clinical immune function and thymus status were available in 218 patients. Only 4 of these were classified as having a major immune function abnormality. Two of these had died, with severe immunodeficiency being the cause of death in 1. A total of 94 of 548 patients had minor abnormalities of the skeletal system, and 39 of 548 had ocular anomalies. Ten offspring comparisons showed that 27 of 35 children had more severe congenital heart disease than their parents, with 8 of 35 having the same degree of severity. Developmental status was worse in 9 of 17 and the same in 7 of 17. Palatal abnormalities were better in 10 of 22 children and similar to the parents in 12 of 22 children. Sibship comparisons in 26 sibs from 12 families showed considerable variation in heart abnormalities between sibs, and development status was similar in most cases. <a href="#58" class="mim-tip-reference" title="Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others. &lt;strong&gt;Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.&lt;/strong&gt; J. Med. Genet. 34: 798-804, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9350810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9350810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.10.798&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9350810">Ryan et al. (1997)</a> concluded that most of the clinical findings in their study reflected previous reports; however, fewer immunologic problems and more renal problems than were expected were found. <a href="#58" class="mim-tip-reference" title="Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others. &lt;strong&gt;Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.&lt;/strong&gt; J. Med. Genet. 34: 798-804, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9350810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9350810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.10.798&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9350810">Ryan et al. (1997)</a> therefore recommended that abdominal ultrasound be carried out in all patients with 22q11 deletions. They also recommended that both parents be studied when a child is found to have a deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9350810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#80" class="mim-tip-reference" title="Vincent, M.-C., Heitz, F., Tricoire, J., Bourrouillou, G., Kuhlein, E., Rolland, M., Calvas, P. &lt;strong&gt;22q deletion in DGS/VCFS monozygotic twins with discordant phenotypes.&lt;/strong&gt; Genet. Counsel. 10: 43-49, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10191428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10191428&lt;/a&gt;]" pmid="10191428">Vincent et al. (1999)</a> reported the case of female monozygotic twins with 22q11 deletions. The twins shared facial characteristics of DGS/VCFS and immunologic defect. However, only one, who died on day 5, had a cardiac defect, composed of an interrupted aortic arch with a ventricular septal defect, a truncus arteriosus, and a large arterial duct. The authors stated that this was the fourth report of a discrepant cardiac status between monozygotic twins harboring 22q11 deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10191428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#84" class="mim-tip-reference" title="Worthington, S., Colley, A., Fagan, K., Dai, K., Lipson, A. H. &lt;strong&gt;Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?&lt;/strong&gt; J. Med. Genet. 34: 79-82, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9032655/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9032655&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.1.79&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9032655">Worthington et al. (1997)</a> reported 3 cases of VCFS with anal anomalies (2 cases of anal stenosis and one of a covered anus with a perineal fistula) and confirmed deletions of the 22q11 region by FISH. They presented an additional case of a child with clinical VCFS whose father was born with an imperforate anus and had mental retardation presumably because of VCFS; this family had been lost to follow-up. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9032655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Devriendt, K., Moerman, P., Van Schoubroeck, D., Vandenberghe, K., Fryns, J.-P. &lt;strong&gt;Chromosome 22q11 deletion presenting as the Potter sequence.&lt;/strong&gt; J. Med. Genet. 34: 423-425, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9152843/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9152843&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.5.423&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9152843">Devriendt et al. (1997)</a> reported a female fetus with Potter sequence caused by unilateral renal agenesis and contralateral multicystic renal dysplasia. Additionally, there was agenesis of the uterus and oviducts (Von Mayer-Rokitansky-Kuster anomaly). The father had dysmorphic features typical of VCFS, and fluorescence in situ hybridization analysis confirmed deletions of chromosome 22q11 in both father and fetus. The fetus had no dysmorphic features suggestive of VCFS and no cardiovascular abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9152843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#73" class="mim-tip-reference" title="Sundaram, U. T., McDonald-McGinn, D. M., Huff, D., Emanuel, B. S., Zackai, E. H., Driscoll, D. A., Bodurtha, J. &lt;strong&gt;Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome.&lt;/strong&gt; Am. J. Med. Genet. 143A: 2016-2018, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17676598/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17676598&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31736&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17676598">Sundaram et al. (2007)</a> described 2 patients with 22q11.2 deletion who had absent uterus and unilateral renal agenesis. One patient also had mild developmental delay, hypoparathyroidism, and psychiatric symptoms; the other patient also had high-arched palate, bulbous nasal tip, bicuspid aortic valve, short stature, and primary amenorrhea. <a href="#73" class="mim-tip-reference" title="Sundaram, U. T., McDonald-McGinn, D. M., Huff, D., Emanuel, B. S., Zackai, E. H., Driscoll, D. A., Bodurtha, J. &lt;strong&gt;Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome.&lt;/strong&gt; Am. J. Med. Genet. 143A: 2016-2018, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17676598/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17676598&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31736&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17676598">Sundaram et al. (2007)</a> suggested that mullerian or uterine/vaginal agenesis be included as part of the clinical spectrum of 22q11.2 deletion syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17676598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#78" class="mim-tip-reference" title="Van Geet, C., Devriendt, K., Eyskens, B., Vermylen, J., Hoylaerts, M. F. &lt;strong&gt;Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets.&lt;/strong&gt; Pediat. Res. 44: 607-611, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9773854/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9773854&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-199810000-00023&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9773854">Van Geet et al. (1998)</a> studied a family in which all 3 members with a 22q11 microdeletion and VCFS had giant platelets and a mild decrease in platelet number. Platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. They studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Since patients with 22q11 deletion are expected to be heterozygous for deletion of the GP1BB gene (<a href="/entry/138720">138720</a>), they can be considered to be carriers of the Bernard-Soulier syndrome (<a href="/entry/231200">231200</a>). A significant increase in platelet size may be a positive predictor for the clinical diagnosis of VCFS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9773854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Digilio, M. C., Marino, B., Cappa, M., Cambiaso, P., Giannotti, A., Dallapiccola, B. &lt;strong&gt;Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome (deletion 22q11.2 syndrome).&lt;/strong&gt; Genet. Med. 3: 30-33, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11339374/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11339374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00125817-200101000-00007&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11339374">Digilio et al. (2001)</a> reported on the growth parameters of 73 patients with the 22q11 deletion. In general, these patients were characterized by weight deficiency in the first years of life, weight normalization in the following years, development of obesity in adolescence, short stature in 10% of the patients, normal height in adolescents, slight delay in bone age in infancy, and microcephaly in 10% of the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Jawad, A. F., McDonald-McGinn, D. M., Zackai, E., Sullivan, K. E. &lt;strong&gt;Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).&lt;/strong&gt; J. Pediat. 139: 715-723, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11713452/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11713452&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.118534&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11713452">Jawad et al. (2001)</a> studied 195 patients with chromosome 22q11.2 deletion syndrome and found that diminished T-cell counts in the peripheral blood are common. The pattern of changes seen with aging in normal control patients was also seen in patients with the chromosome 22q11.2 deletion syndrome, although the decline in T cells was blunted. Autoimmune disease was seen in most age groups, although the types of disorders varied according to age. Infections were also common in older patients, although they were seldom life-threatening. Juvenile rheumatoid arthritis with onset between 1.5 and 6 years of age was seen in 4 of the 195 patients; idiopathic thrombocytopenia purpura with onset at 1 to 8 years of age was seen in 8 of 195 patients; autoimmune hemolytic anemia, psoriasis, vitiligo, inflammatory bowel disease, adult rheumatoid arthritis, and rheumatic fever with chorea were each seen in 1 patient of the 195 patients sampled. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11713452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Kawame, H., Adachi, M., Tachibana, K., Kurosawa, K., Ito, F., Gleason, M. M., Weinzimer, S., Levitt-Katz, L., Sullivan, K., McDonald-McGinn, D. M. &lt;strong&gt;Graves&#x27; disease in patients with 22q11.2 deletion.&lt;/strong&gt; J. Pediat. 139: 892-895, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11743521/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11743521&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.119448&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11743521">Kawame et al. (2001)</a> reported 5 patients with chromosome 22q11.2 deletion that manifested Graves disease between the ages of 27 months and 16 years, and suggested that Graves disease may be part of the clinical spectrum of this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11743521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="McElhinney, D. B., McDonald-McGinn, D., Zackai, E. H., Goldmuntz, E. &lt;strong&gt;Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age.&lt;/strong&gt; Pediatrics 108: e104, 2001. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11731631/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11731631&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.108.6.e104&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11731631">McElhinney et al. (2001)</a> studied 29 patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age to determine the incidence of cardiovascular anomalies. In 11 of 29 (38%) patients, cardiovascular anomalies were detected, including 3 with a vascular ring, 3 with a right aortic arch with mirror-image branching of the brachiocephalic arteries (no vascular ring; one with a patent ductus arteriosus; see <a href="/entry/607411">607411</a>), and 4 with a left aortic arch with an aberrant right subclavian artery (no vascular ring; 1 with a patent ductus), and 1 with a left superior vena cava draining to the coronary sinus. All 3 patients with vascular rings and 1 with a patent ductus arteriosus required intervention, giving an incidence of 14% in this study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Kessler-Icekson, G., Birk, E., Weintraub, A. Y., Barhum, Y., Kotlyar, V., Schlesinger, H., Rockah, R., Vidne, B. A., Frisch, A. &lt;strong&gt;Association of tetralogy of Fallot with a distinct region of del22q11.2.&lt;/strong&gt; Am. J. Med. Genet. 107: 294-298, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11840485/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11840485&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.10166&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11840485">Kessler-Icekson et al. (2002)</a> examined myocardial tissues removed after corrective surgery of 31 patients with congenital heart defects (21 with tetralogy of Fallot and 10 with a double-chamber right ventricle) using a set of 9 polymorphic short tandem repeat markers along the 22q11.2 region. Ten (48%) of the tetralogy of Fallot patients had homozygosity for 3 or more consecutive markers, suggesting possible 22q11.2 deletions. None of the patients with double-chamber right ventricle had this finding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Martin, B., Fananas, L., Gutierrez, B., Chow, E. W. C., Bassett, A. S. &lt;strong&gt;Dermatoglyphic profile in 22q deletion syndrome.&lt;/strong&gt; Am. J. Med. Genet. 128B: 46-49, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15211630/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15211630&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.b.30034&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15211630">Martin et al. (2004)</a> identified an altered dermatoglyphic profile in 22q deletion syndrome patients, which involved (1) ATD angle and amplitude, (2) the presence of radial loops in the hypothenar area, and (3) fluctuating asymmetry. <a href="#45" class="mim-tip-reference" title="Martin, B., Fananas, L., Gutierrez, B., Chow, E. W. C., Bassett, A. S. &lt;strong&gt;Dermatoglyphic profile in 22q deletion syndrome.&lt;/strong&gt; Am. J. Med. Genet. 128B: 46-49, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15211630/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15211630&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.b.30034&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15211630">Martin et al. (2004)</a> noted that the first 2 features are similar to those found in other genetic syndromes associated with low IQ, whereas high levels of fluctuating asymmetry have often been reported in schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15211630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#61" class="mim-tip-reference" title="Sandrin-Garcia, P., Macedo, C., Martelli, L. R., Ramos, E. S., Guion-Almeida, M. L., Richieri-Costa, A., Passos, G. A. S. &lt;strong&gt;Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome.&lt;/strong&gt; Clin. Genet. 61: 380-383, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12081724/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12081724&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1034/j.1399-0004.2002.610511.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12081724">Sandrin-Garcia et al. (2002)</a> described a family in which a patient had the clinical diagnosis of VCFS and his sister had a suggestive phenotype. Both were found to carry a deletion in 22q11.2 of maternal origin. The mother and other unaffected relatives did not show the deletion, suggesting that the mother had gonadal mosaicism with a normal DNA profile in the blood cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12081724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Conway, K., Gibson, R. L., Perkins, J., Cunningham, M. L. &lt;strong&gt;Pulmonary agenesis: expansion of the VCFS phenotype.&lt;/strong&gt; Am. J. Med. Genet. 113: 89-92, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12400071/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12400071&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.10673&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12400071">Conway et al. (2002)</a> described a child with the typical craniofacial manifestations of VCFS and unilateral pulmonary agenesis. They suggested that the patient's pulmonary agenesis was related to a disruption of the dorsal aortic arch development that selectively interfered with lung bud growth and, further, that pulmonary agenesis should be considered part of the spectrum of malformations seen in 22q11.2 deletion. <a href="#10" class="mim-tip-reference" title="Cunningham, M. L., Perry, R. J., Eby, P. R., Gibson, R. L., Opheim, K. E., Manning, S. C. &lt;strong&gt;Primary pulmonary dysgenesis in velocardiofacial syndrome: a second patient. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 121A: 177-179, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910501/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12910501&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20142&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12910501">Cunningham et al. (2003)</a> reported a second patient with VCFS, confirmed by genetic detection of 22q11.2 deletion, and unilateral primary pulmonary agenesis. High-resolution CT imaging showed a hypoplastic left lung comprising a single lobe, small left bronchus, hypoplastic left pulmonary artery, and hypoplastic left chest wall with complete shift of the trachea and mediastinum into the left hemithorax. The patient also had congenital conductive hearing loss due to malformation and subluxation of the left stapes, and hypoplasia of the left mandible. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12910501+12400071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., Gatzoulis, M. A. &lt;strong&gt;Clinical features of 78 adults with 22q11 deletion syndrome.&lt;/strong&gt; Am. J. Med. Genet. 138A: 307-313, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16208694/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16208694&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16208694[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30984&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16208694">Bassett et al. (2005)</a> described the phenotypic features of 78 adults with 22q11 deletion syndrome and identified 43 distinct features present in more than 5% of patients. Common characteristic features included intellectual disabilities (92.3%), hypocalcemia (64%), palatal anomalies (42%), and cardiovascular anomalies (25.8%). Other less commonly appreciated features included obesity (35%), hypothyroidism (20.5%), hearing deficits (28%), cholelithiasis (19%), scoliosis (47%), and dermatologic abnormalities (severe acne, 23%; seborrhea, 35%). Significantly, schizophrenia was present in 22.6% of patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16208694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neuropsychologic Features</em></strong></p><p>
<a href="#24" class="mim-tip-reference" title="Golding-Kushner, K. J., Weller, G., Shprintzen, R. J. &lt;strong&gt;Velo-cardio-facial syndrome: language and psychological profiles.&lt;/strong&gt; J. Craniofac. Genet. Dev. Biol. 5: 259-266, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4044789/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4044789&lt;/a&gt;]" pmid="4044789">Golding-Kushner et al. (1985)</a> observed that children with VCFS had 'characteristic personality features,' which were described as blunt or inappropriate affect, and that a greater than expected number of these children developed severe psychiatric illnesses as they approached adolescence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4044789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#67" class="mim-tip-reference" title="Shprintzen, R. J., Goldberg, R., Golding-Kushner, K. J., Marion, R. &lt;strong&gt;Late-onset psychosis in the velo-cardio-facial syndrome.&lt;/strong&gt; Am. J. Med. Genet. 42: 141-142, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1308357/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1308357&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320420131&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1308357">Shprintzen et al. (1992)</a> pointed out that psychotic illness is a feature of VCFS in adolescents or adults. In a pilot study of patients diagnosed with VCFS and their relatives, <a href="#56" class="mim-tip-reference" title="Pulver, A. E., Nestadt, G., Goldberg, R., Shprintzen, R. J., Lamacz, M., Wolyniec, P. S., Morrow, B., Karayiogou, M., Antonarakis, S. E., Housman, D., Kucherlapati, R. &lt;strong&gt;Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.&lt;/strong&gt; J. Nerv. Ment. Dis. 182: 476-478, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8040660/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8040660&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00005053-199408000-00010&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8040660">Pulver et al. (1994)</a> found a high rate of psychosis among the patients and their relatives, suggesting that there may be a gene associated with schizophrenia (see <a href="/entry/181500">181500</a>) on chromosome 22q or that a DNA rearrangement in this region may be important to the etiology of some forms of schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8040660+1308357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Kok, L. L., Solman, R. T. &lt;strong&gt;Velocardiofacial syndrome: learning difficulties and intervention.&lt;/strong&gt; J. Med. Genet. 32: 612-618, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7473652/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7473652&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.8.612&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7473652">Kok and Solman (1995)</a> emphasized the usefulness of interactive computer-based instruction for the development of reading, language, spelling, and numeracy skills in VCFS individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7473652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#83" class="mim-tip-reference" title="Woodin, M., Wang, P. P., Aleman, D., McDonald-McGinn, D., Zackai, E., Moss, E. &lt;strong&gt;Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion.&lt;/strong&gt; Genet. Med. 3: 34-39, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11339375/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11339375&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00125817-200101000-00008&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11339375">Woodin et al. (2001)</a> reported updated findings of neuropsychologic data from 80 children with the 22q11 deletion. The subjects showed higher verbal than nonverbal IQ scores, assets in verbal memory, and deficits in the areas of attention, story memory, visuospatial memory, arithmetic performance relative to other areas of achievement, and psychosocial functioning. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Gothelf, D., Presburger, G., Levy, D., Nahmani, A., Burg, M., Berant, M., Blieden, L. C., Finkelstein, Y., Frisch, A., Apter, A., Weizman, A. &lt;strong&gt;Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome.&lt;/strong&gt; Am. J. Med. Genet. 126B: 116-121, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15048660/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15048660&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.b.20144&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15048660">Gothelf et al. (2004)</a> studied 43 patients with VCFS for obsessive-compulsive symptoms, using the Yale-Brown obsessive compulsive scale and a semistructured psychiatric interview. Fourteen of the subjects (32.6%) met DSM-IV criteria for obsessive-compulsive disorder (OCD; see <a href="/entry/164230">164230</a>); in these patients, the symptoms began at an early age and generally responded to fluoxetine treatment. Additionally, 16 of the patients (37.2%) had attention-deficit hyperactivity disorder (ADHD; see <a href="/entry/143465">143465</a>) and 7 (16.2%) had a psychotic disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15048660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Gothelf, D., Presburger, G., Zohar, A. H., Burg, M., Nahmani, A., Frydman, M., Shohat, M., Inbar, D., Aviram-Goldring, A., Yeshaya, J., Steinberg, T., Finkelstein, Y., Frisch, A., Weizman, A., Apter, A. &lt;strong&gt;Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.&lt;/strong&gt; Am. J. Med. Genet. 126B: 99-105, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15048657/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15048657&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.b.20124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15048657">Gothelf et al. (2004)</a> investigated the association of familial, developmental, and physical factors with the occurrence of ADHD in 51 patients with nonfamilial VCFS. Twenty-one patients (41.2%) were diagnosed with ADHD. There was a significantly greater prevalence of ADHD in the first-degree relatives of patients with ADHD than in those without (odds ratio, 5.9, 95% CI, 1.6-22.1; p = 0.006). ADHD and non-ADHD groups had similar IQ scores (total, verbal, and performance) and had a similar average degree of severity of facial dysmorphism and cardiac and cleft anomalies. <a href="#27" class="mim-tip-reference" title="Gothelf, D., Presburger, G., Zohar, A. H., Burg, M., Nahmani, A., Frydman, M., Shohat, M., Inbar, D., Aviram-Goldring, A., Yeshaya, J., Steinberg, T., Finkelstein, Y., Frisch, A., Weizman, A., Apter, A. &lt;strong&gt;Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.&lt;/strong&gt; Am. J. Med. Genet. 126B: 99-105, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15048657/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15048657&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.b.20124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15048657">Gothelf et al. (2004)</a> suggested that there is a genetic contribution to ADHD in VCFS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15048657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Evers, L. J. M., Vermaak, M. P., Engelen, J. J. M., Curfs, L. M. G. &lt;strong&gt;The velocardiofacial syndrome in older age: dementia and autistic features.&lt;/strong&gt; Genet. Counsel. 17: 333-340, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17100202/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17100202&lt;/a&gt;]" pmid="17100202">Evers et al. (2006)</a> reported a 52-year-old man with 22q11.2 deletion. As a child he showed learning disabilities and behavioral problems. As a young adult, he exhibited aggressive outbursts, apathy, echolalia, perseverations, and psychotic features, including delusional thoughts and hallucinations, necessitating long-term care in a psychiatric facility. Since then, he has demonstrated aggressive behavior, periods of withdrawal, and progressive cognitive decline consistent with dementia, particularly since the age of 36 years. An affected autistic sister also had the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17100202" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Evers, L. J. M., De Die-Smulders, C. E. M., Smeets, E. E. J., Clerkx, M. G. M., Curfs, L. M. G. &lt;strong&gt;The velo-cardio-facial syndrome: the spectrum of psychiatric problems and cognitive deterioration at adult age.&lt;/strong&gt; Genet. Counsel. 20: 307-315, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20162865/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20162865&lt;/a&gt;]" pmid="20162865">Evers et al. (2009)</a> reported 7 unrelated adult patients with the 22q11.2 deletion and low cognitive function. Most had psychotic episodes in their young adult lives followed by intellectual decline. Other variable features included paranoia, aggression, mood swings, destructive behavior, autistic disorder, and dementia. At the time of the report, all were living in long-term residential care. All presented with intellectual disability, which later developed into more severe psychiatric illnesses, leading to the correct molecular diagnosis later in life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20162865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Butcher, N. J., Chow, E. W. C., Costain, G., Karas, D., Ho, A., Bassett, A. S. &lt;strong&gt;Functional outcomes of adults with 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 14: 836-843, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22744446/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22744446&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2012.66&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22744446">Butcher et al. (2012)</a> used the Vineland Adaptive Behavior Scales to assess functioning in 100 adults with 22q11.2 deletion syndrome (46 males; mean age = 28.8 (SD = 9.7) years) where intellect ranged from average to borderline (57 individuals) to mild intellectual disability (43 individuals). More than 75% of the subjects scored in the functional deficit range. Although personal, vocational, and financial demographics confirmed widespread functional impairment, daily living skills and employment were relative strengths. Intelligence quotient was a significant predictor (p less than 0.001) of overall and domain-specific adaptive functioning skills. A diagnosis of schizophrenia was a significant predictor (p less than 0.05) of overall adaptive functioning, daily living skills, and socialization scores. Notably, congenital heart disease, history of mood/anxiety disorders, sex, and age were not significant predictors of functioning. <a href="#5" class="mim-tip-reference" title="Butcher, N. J., Chow, E. W. C., Costain, G., Karas, D., Ho, A., Bassett, A. S. &lt;strong&gt;Functional outcomes of adults with 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 14: 836-843, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22744446/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22744446&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2012.66&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22744446">Butcher et al. (2012)</a> concluded that, despite functional impairment in adulthood that is primarily mediated by cognitive and psychiatric phenotypes, relative strengths in activities of daily living and employment have important implications for services and long-term planning in patients with 22q11.2 deletion syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22744446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#79" class="mim-tip-reference" title="Van, L., Butcher, N. J., Costain, G., Ogura, L., Chow, E. W. C., Bassett, A. S. &lt;strong&gt;Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 18: 350-355, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26087175/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26087175&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2015.84&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26087175">Van et al. (2016)</a> investigated the relationship of small for gestational age (SGA) birth weight (less than 3rd percentile for sex and gestational age) and prematurity (less than 37 weeks' gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11 deletion syndrome. SGA birth weight (OR = 3.52, 95% CI 1.34-9.22) and prematurity (OR = 5.38, 95% CI = 1.63-17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2 deletion syndrome. Being born SGA or premature resulted in a positive predictive value of 46% for schizophrenia; negative predictive value in the absence of both features was 83%. Post hoc analyses suggested that these perinatal complications were also associated with factors indicative of increased severity of schizophrenia. <a href="#79" class="mim-tip-reference" title="Van, L., Butcher, N. J., Costain, G., Ogura, L., Chow, E. W. C., Bassett, A. S. &lt;strong&gt;Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 18: 350-355, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26087175/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26087175&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2015.84&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26087175">Van et al. (2016)</a> concluded that in 22q11.2 deletion syndrome, fetal growth and gestation may have a clinically significant impact on future risk of schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26087175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="biochemicalFeatures" class="mim-anchor"></a>
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#25" class="mim-tip-reference" title="Goodman, B. K., Rutberg, J., Lin, W. W., Pulver, A. E., Thomas, G. H., Geraghty, M. T. &lt;strong&gt;Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome.&lt;/strong&gt; J. Inherit. Metab. Dis. 23: 847-848, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11196113/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11196113&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026773005303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11196113">Goodman et al. (2000)</a> reported that 8 of 15 patients with deletions in the VCF critical region 22q11.2 had elevated proline levels ranging from 278 to 849 micromol/l while 7 were in the normal range of 51 to 271 micromol/l. <a href="#25" class="mim-tip-reference" title="Goodman, B. K., Rutberg, J., Lin, W. W., Pulver, A. E., Thomas, G. H., Geraghty, M. T. &lt;strong&gt;Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome.&lt;/strong&gt; J. Inherit. Metab. Dis. 23: 847-848, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11196113/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11196113&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026773005303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11196113">Goodman et al. (2000)</a> suggested that the hyperprolinemia (<a href="/entry/239500">239500</a>) is caused by the hemizygous deletion of the proline oxidase gene (<a href="/entry/606810">606810</a>) that maps to this region. <a href="#25" class="mim-tip-reference" title="Goodman, B. K., Rutberg, J., Lin, W. W., Pulver, A. E., Thomas, G. H., Geraghty, M. T. &lt;strong&gt;Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome.&lt;/strong&gt; J. Inherit. Metab. Dis. 23: 847-848, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11196113/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11196113&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1026773005303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11196113">Goodman et al. (2000)</a> concluded that elevations in plasma proline levels should be considered a biochemical feature of the chromosome 22q11.2 deletion syndromes and suggested that patients with isolated hyperprolinemia should be studied for the microdeletion at 22q11.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>VCFS is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is the routine screening for 22q11 deletions in all infants with cleft palate (CP). <a href="#57" class="mim-tip-reference" title="Ruiter, E. M., Bongers, E. M. H. F., Smeets, D. F. C. M., Kuijpers-Jagtman, A. M., Hamel, B. C. J. &lt;strong&gt;No justification of routine screening for 22q11 deletions in patients with overt cleft palate.&lt;/strong&gt; Clin. Genet. 64: 216-219, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12919136/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12919136&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1034/j.1399-0004.2003.00134.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12919136">Ruiter et al. (2003)</a> evaluated this strategy as opposed to testing on clinical suspicion alone. At the Nijmegen Cleft Palate Craniofacial Center in the Netherlands, they routinely tested 58 new patients with overt CP, using FISH, for the 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study and the literature, they estimated the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, to be 1 in 99. They concluded that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12919136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="cytogenetics" class="mim-anchor"></a>
<h4 href="#mimCytogeneticsFold" id="mimCytogeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimCytogeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Cytogenetics</strong>
</span>
</h4>
</div>
<div id="mimCytogeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The large clinical overlap between DiGeorge syndrome and velocardiofacial syndrome suggested an etiologic connection. DiGeorge syndrome is associated with microdeletions of chromosome 22q11 and is thought to be caused by reduced dosage of genes within this region, i.e., monosomy. <a href="#62" class="mim-tip-reference" title="Scambler, P. J., Kelly, D., Lindsay, E., Williamson, R., Goldberg, R., Shprintzen, R., Wilson, D. I., Goodship, J. A., Cross, I. E., Burn, J. &lt;strong&gt;Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus.&lt;/strong&gt; Lancet 339: 1138-1139, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1349369/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1349369&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0140-6736(92)90734-k&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1349369">Scambler et al. (1992)</a> presented preliminary evidence of similar microdeletions in 22q11 in patients with VCF syndrome. <a href="#35" class="mim-tip-reference" title="Kelly, D., Goldberg, R., Wilson, D., Lindsay, E., Carey, A., Goodship, J., Burn, J., Cross, I., Shprintzen, R. J., Scambler, P. J. &lt;strong&gt;Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.&lt;/strong&gt; Am. J. Med. Genet. 45: 308-312, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434616/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434616&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450306&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434616">Kelly et al. (1993)</a> found monosomy for a region of 22q11 in all 12 patients with VCFS who were examined by use of DNA probes. By high-resolution banding techniques, <a href="#14" class="mim-tip-reference" title="Driscoll, D. A., Spinner, N. B., Budarf, M. L., McDonald-McGinn, D. M., Zackai, E. H., Goldberg, R. B., Shprintzen, R. J., Saal, H. M., Zonana, J., Jones, M. C., Mascarello, J. T., Emanuel, B. S. &lt;strong&gt;Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome.&lt;/strong&gt; Am. J. Med. Genet. 44: 261-268, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1360769/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1360769&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440237&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1360769">Driscoll et al. (1992)</a> detected an interstitial deletion of 22q11.21-q11.23 in 3 of 15 patients with VCFS. The remaining 12 patients had apparently normal chromosomes. Molecular analysis with probes from the DiGeorge chromosome region (DGCR) within 22q11 detected DNA deletions in 14 of the 15 patients. In 2 families, deletions were detected in the affected parent as well as the proband, suggesting autosomal dominant transmission of VCFS due to segregation of a deletion. Thus, further support is provided that VCFS and DGS may be the result of mutation in the same gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1349369+8434616+1360769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., Lasseter, V. K., Eisen, H., Childs, B., Kazazian, H. H., Kucherlapati, R., Antonarakis, S. E., Pulver, A. E., Housman, D. E. &lt;strong&gt;Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.&lt;/strong&gt; Proc. Nat. Acad. Sci. 92: 7612-7616, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7644464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7644464&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.92.17.7612&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7644464">Karayiorgou et al. (1995)</a> reported the results of 2 studies examining the genetic overlap between schizophrenia and VCFS. In the first study, they characterized 2 interstitial deletions identified on 22q11 in a sample of schizophrenic patients. The size of the deletions were estimated to be between 1.5 and 2 Mb. In the second study, they investigated whether variations in deletion size are associated with the schizophrenic phenotype in VCFS patients. The results suggested that a region of the genome that had previously been implicated by genetic linkage analysis may harbor genetic lesions that increase the susceptibility to schizophrenia. See <a href="/entry/600850">600850</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7644464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, <a href="#7" class="mim-tip-reference" title="Carlson, C., Papolos, D., Pandita, R. K., Faedda, G. L., Veit, S., Goldberg, R., Shprintzen, R., Kucherlapati, R., Morrow, B. &lt;strong&gt;Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.&lt;/strong&gt; Am. J. Hum. Genet. 60: 851-859, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9106531/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9106531&lt;/a&gt;]" pmid="9106531">Carlson et al. (1997)</a> evaluated 26 VCFS patients by clinical and molecular biologic methods. The VCFS children and adolescents were found to share psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients (more than 18 years of age) were affected with bipolar spectrum disorders. Four of 6 adult patients had psychotic symptoms manifested by paranoid and grandiose delusions. Loss of heterozygosity (LOH) analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and 2 did not have a detectable deletion, even when analyzed with a large number of sequence tagged sites (STSs) at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggested a common genetic etiology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#51" class="mim-tip-reference" title="Morrow, B., Goldberg, R., Carlson, C., Das Gupta, R., Sirotkin, H., Collins, J., Dunham, I., O&#x27;Donnell, H., Scambler, P., Shprintzen, R., Kucherlapati, R. &lt;strong&gt;Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 56: 1391-1403, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7762562/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7762562&lt;/a&gt;]" pmid="7762562">Morrow et al. (1995)</a> used 11 short tandem-repeat polymorphic (STRP) markers to study 15 VCFS individuals and their unaffected parents. Haplotypes generated by these markers revealed that 82% of the patients had deletions. All patients who had a deletion shared a common proximal breakpoint, while there were 2 distinct distal breakpoints. Markers D22S941 and D22S944 appeared to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. Parental origin of the deleted chromosome had no effect on the phenotypic manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11, <a href="#8" class="mim-tip-reference" title="Carlson, C., Sirotkin, H., Pandita, R., Goldberg, R., McKie, J., Wadey, R., Patanjali, S. R., Weissman, S. M., Anyane-Yeboa, K., Warburton, D., Scambler, P., Shprintzen, R., Kucherlapati, R., Morrow, B. E. &lt;strong&gt;Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.&lt;/strong&gt; Am. J. Hum. Genet. 61: 620-629, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326327/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9326327&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/515508&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9326327">Carlson et al. (1997)</a> found that 83% had a deletion and more than 90% of these had a similar deletion of approximately 3 Mb, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. They found no correlation between the presence or size of the deletion and the phenotype. To define further the chromosomal breakpoints among the VCFS patients, they developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that included deletion breakpoints was constructed, incorporating genes and ESTs isolated by the hybridization selection method. The ordered markers were used to examine the 2 separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, they could map the chromosome breakpoints within a single cosmid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Edelmann, L., Pandita, R. K., Spiteri, E., Funke, B., Goldberg, R., Palanisamy, N., Chaganti, R. S. K., Magenis, E., Shprintzen, R. J., Morrow, B. E. &lt;strong&gt;A common molecular basis for rearrangement disorders on chromosome 22q11.&lt;/strong&gt; Hum. Molec. Genet. 8: 1157-1167, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10369860/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10369860&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/8.7.1157&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10369860">Edelmann et al. (1999)</a> developed hamster-human somatic hybrid cell lines from VCFS/DGS patients and showed by use of haplotype analysis with a set of 16 ordered genetic markers on 22q11 that the breakpoints occurred within similar low copy repeats, designated LCR22s. Models were presented to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#65" class="mim-tip-reference" title="Shaikh, T. H., Kurahashi, H., Saitta, S. C., O&#x27;Hare, A. M., Hu, P., Roe, B. A., Driscoll, D. A., McDonald-McGinn, D. M., Zackai, E. H., Budarf, M. L., Emanuel, B. S. &lt;strong&gt;Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.&lt;/strong&gt; Hum. Molec. Genet. 9: 489-501, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10699172/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10699172&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/9.4.489&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10699172">Shaikh et al. (2000)</a> completed sequencing of the 3-Mb typically deleted region (TDR) and identified 4 LCRs within it. Although the LCRs differed in content and organization of shared modules, those modules that were common between them shared 97 to 98% sequence identity with one another. Sequence analysis of rearranged junction fragments from variant deletions in 3 DGS/VCFS patients implicated the LCRs directly in the formation of 22q11.2 deletions. FISH analysis of nonhuman primates suggested that the duplication events which generated the nest of LCRs may have occurred at least 20 to 25 million years ago. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#60" class="mim-tip-reference" title="Saitta, S. C., Harris, S. E., Gaeth, A. P., Driscoll, D. A., McDonald-McGinn, D. M., Maisenbacher, M. K., Yersak, J. M., Chakraborty, P. K., Hacker, A. M., Zackai, E. H., Ashley, T., Emanuel, B. S. &lt;strong&gt;Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion.&lt;/strong&gt; Hum. Molec. Genet. 13: 417-428, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14681306/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14681306&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14681306[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddh041&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14681306">Saitta et al. (2004)</a> traced the grandparental origin of regions flanking de novo 3-Mb deletions in 20 informative 3-generation families with DiGeorge or velocardiofacial syndromes. Haplotype reconstruction of the flanking regions showed an unexpectedly high number of proximal interchromosomal exchanges between homologs, occurring in 19 of 20 families, whereas the normal chromosome 22 in these probands showed interchromosomal exchanges in 2 of 15 informative meioses, a rate consistent with the genetic distance. Immunostaining with MLH1 (<a href="/entry/120436">120436</a>) antibody localized meiotic exchanges to the distal region of chromosome 22q in 75% of human spermatocytes tested, also reflecting the genetic map. There was no effect of proband gender or parental age on crossover frequency, and parental origin studies in 65 de novo 3-Mb deletions demonstrated no bias. Unlike Williams syndrome (<a href="/entry/194050">194050</a>), FISH analysis showed no chromosomal inversions flanked by LCRs in 22 sets of parents of 22q11-deleted patients or in 8 nondeleted patients with a DGS/VCFS phenotype. <a href="#60" class="mim-tip-reference" title="Saitta, S. C., Harris, S. E., Gaeth, A. P., Driscoll, D. A., McDonald-McGinn, D. M., Maisenbacher, M. K., Yersak, J. M., Chakraborty, P. K., Hacker, A. M., Zackai, E. H., Ashley, T., Emanuel, B. S. &lt;strong&gt;Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion.&lt;/strong&gt; Hum. Molec. Genet. 13: 417-428, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14681306/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14681306&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14681306[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddh041&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14681306">Saitta et al. (2004)</a> concluded that significant aberrant interchromosomal exchange events during meiosis I in the proximal region of the affected chromosome 22 are the likely etiology for these deletions. Since this type of exchange occurs more often for 22q11 deletions than for deletions of 7q11, 15q11, 17p11, and 17q11, they suggested that there is a difference in the meiotic behavior of chromosome 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#59" class="mim-tip-reference" title="Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G. &lt;strong&gt;Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.&lt;/strong&gt; Genet. Med. 13: 868-880, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21792059/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21792059&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182217a06&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21792059">Sahoo et al. (2011)</a> analyzed 38,779 individuals referred to the diagnostic laboratory for microarray testing for the presence of copy number variants encompassing 20 putative schizophrenia susceptibility loci. They also analyzed the indications for study for individuals with copy number variants overlapping those found in 6 individuals referred for schizophrenia. After excluding larger gains or losses that encompassed additional genes outside the candidate loci (e.g., whole-arm gains/losses), <a href="#59" class="mim-tip-reference" title="Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G. &lt;strong&gt;Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.&lt;/strong&gt; Genet. Med. 13: 868-880, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21792059/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21792059&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182217a06&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21792059">Sahoo et al. (2011)</a> identified 1,113 individuals with copy number variants encompassing schizophrenia susceptibility loci and 37 individuals with copy number variants overlapping those present in the 6 individuals referred for schizophrenia. Of these, 1,035 had a copy number variant of 1 of 6 recurrent loci: 1q21.1 (<a href="/entry/612474">612474</a>, <a href="/entry/612475">612475</a>), 15q11.2 (<a href="/entry/608636">608636</a>), 15q13.3 (<a href="/entry/612001">612001</a>), 16p11.2 (<a href="/entry/611913">611913</a>), 16p13.11 (<a href="/entry/610543">610543</a>, <a href="/entry/613458">613458</a>), and 22q11.2 (see also <a href="/entry/608363">608363</a>). The indications for study for these 1,150 individuals were diverse and included developmental delay, intellectual disability, autism spectrum, and multiple congenital anomalies. <a href="#59" class="mim-tip-reference" title="Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G. &lt;strong&gt;Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.&lt;/strong&gt; Genet. Med. 13: 868-880, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21792059/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21792059&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182217a06&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21792059">Sahoo et al. (2011)</a> identified the 22q11.2 microdeletion in 186 individuals; 38 were de novo, 4 maternally inherited, 4 paternally inherited, and 140 of unknown inheritance. The average age at diagnosis was 7.1 years with an age range of 0.2 to 50.1 years, and the indications for study included development delay, behavioral abnormalities, dysmorphic features, multiple congenital anomalies, congenital heart defect, failure to thrive, autism, hypocalcemia, seizure disorder, postaxial polydactyly, and clubfeet. This deletion was seen in 115 of 23,250 cases referred to their laboratory for a frequency of 0.49%, and not at all in 5,674 controls for a p value of less than 0.0001 (see <a href="#29" class="mim-tip-reference" title="Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., Mefford, H., Ying, P., Nickerson, D. A., Eichler, E. E. &lt;strong&gt;Population analysis of large copy number variants and hotspots of human genetic disease.&lt;/strong&gt; Am. J. Hum. Genet. 84: 148-161, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19166990/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19166990&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19166990[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2008.12.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19166990">Itsara et al., 2009</a>). The incidence in a schizophrenia population reported by <a href="#37" class="mim-tip-reference" title="Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Owen, M. J., O&#x27;Donovan, M. C. &lt;strong&gt;Support for the involvement of large copy number variants in the pathogenesis of schizophrenia.&lt;/strong&gt; Hum. Molec. Genet. 18: 1497-1503, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19181681/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19181681&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19181681[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp043&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19181681">Kirov et al. (2009)</a> was 0.2% compared to 0.0% in their controls. <a href="#59" class="mim-tip-reference" title="Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G. &lt;strong&gt;Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.&lt;/strong&gt; Genet. Med. 13: 868-880, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21792059/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21792059&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182217a06&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21792059">Sahoo et al. (2011)</a> concluded that the results from their study, the largest genotype-first analysis of schizophrenia susceptibility loci to that time, suggested that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and implied the existence of shared biologic pathways among multiple neurodevelopmental conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19166990+21792059+19181681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="heterogeneity" class="mim-anchor"></a>
<h4 href="#mimHeterogeneityFold" id="mimHeterogeneityToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHeterogeneityToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<div id="mimHeterogeneityFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#76" class="mim-tip-reference" title="Tsai, C.-H., Van Dyke, D. L., Feldman, G. L. &lt;strong&gt;A child with velocardiofacial syndrome and del(4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype.&lt;/strong&gt; Am. J. Med. Genet. 82: 336-339, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10051168/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10051168&lt;/a&gt;]" pmid="10051168">Tsai et al. (1999)</a> reported a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly, features consistent with velocardiofacial syndrome. The child did not have a 22q deletion based on FISH analysis using the probe D22S75; however, cytogenetic analysis demonstrated a terminal deletion of 4q34.2-qter. The authors suggested that a distal 4q deletion may lead to a syndrome similar to velocardiofacial syndrome and emphasized the importance of searching for other chromosome abnormalities when a phenotype of velocardiofacial syndrome is present and a 22q deletion is not detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#77" class="mim-tip-reference" title="Van Esch, H., Groenen, P., Fryns, J.-P., Van de Ven, W., Devriendt, K. &lt;strong&gt;The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome.&lt;/strong&gt; Genet. Counsel. 10: 59-65, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10191430/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10191430&lt;/a&gt;]" pmid="10191430">Van Esch et al. (1999)</a> reviewed 35 cases of del10p13-p14 plus one of their own (see <a href="/entry/601362">601362</a>) and compared the phenotypic spectrum with that of classic DGS/VCFS associated with del22q11 as defined by <a href="#58" class="mim-tip-reference" title="Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others. &lt;strong&gt;Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.&lt;/strong&gt; J. Med. Genet. 34: 798-804, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9350810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9350810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.10.798&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9350810">Ryan et al. (1997)</a>. Both groups of patients may have facial dysmorphism, renal anomalies, hypoparathyroidism, and immune defect. However, severe growth and mental retardation were noted in almost all patients with del10p but not in those with del22q11. Heart defects were less frequent in del10p. A distinct feature in del10p was the presence of progressive sensorineural deafness, whereas in del22q11 the hearing loss was mostly conductive due to palate deformities and velopharyngeal insufficiency. In both groups, the full clinical picture was rarely seen. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9350810+10191430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#6" class="mim-tip-reference" title="Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., Kuhn, P., Arrive, M., Gilch, C., Schmitt, E., Fehrenbach, S., Schnebelen, A., Frebourg, T., Flori, E. &lt;strong&gt;Genetic compensation in a human genomic disorder.&lt;/strong&gt; New Eng. J. Med. 360: 1211-1216, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19297573/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19297573&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa0806544&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19297573">Carelle-Calmels et al. (2009)</a> noted that deletion of 22q11.2, resulting in DGS or VCFS, is usually sporadic but has been reported to be inherited in 6 to 28% of patients with these syndromes. They performed cytogenetic studies of the parents of a girl with DGS (or VCFS) who had a deletion of 22q11.2 and found an unexpected rearrangement of both 22q11.2 regions in the unaffected father. He carried a 22q11.2 deletion on one copy of chromosome 22 and a reciprocal 22q11.2 duplication (see <a href="/entry/608363">608363</a>) on the other copy of chromosome 22. Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the 22q11 deletion syndrome. <a href="#6" class="mim-tip-reference" title="Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., Kuhn, P., Arrive, M., Gilch, C., Schmitt, E., Fehrenbach, S., Schnebelen, A., Frebourg, T., Flori, E. &lt;strong&gt;Genetic compensation in a human genomic disorder.&lt;/strong&gt; New Eng. J. Med. 360: 1211-1216, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19297573/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19297573&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa0806544&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19297573">Carelle-Calmels et al. (2009)</a> noted that this finding has implications for genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19297573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Delio, M., Guo, T., McDonald-McGinn, D. M., Zackai, E., Herman, S., Kaminetzky, M., Higgins, A. M., Coleman, K., Chow, C., Jalbrzikowski, M., Bearden, C. E., Bailey, A., and 45 others. &lt;strong&gt;Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 92: 439-447, 2013. Note: Erratum: Am. J. Hum. Genet. 92: 637 only, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23453669/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23453669&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23453669[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2013.01.018&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23453669">Delio et al. (2013)</a> genotyped a total of 389 DNA samples from 22q11 deletion syndrome-affected families. A total of 219 (56%) individuals with 22q11 deletion had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, similar to data for the general population in 11 countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6 to 1.7 times greater than that for males, suggesting that for this region in the genome enhanced meiotic recombination rates, as well as other 22q11.2-specific features, could be responsible for the observed excess in maternal origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23453669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalManagement" class="mim-anchor"></a>
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>See <a href="#54" class="mim-tip-reference" title="Oskarsdottir, S., Boot, E., Crowley, T. B., Loo, J. C. Y., Arganbright, J. M., Armando, M., Baylis, A. L., Breetvelt, E. J., Castelein, R. M., Chadehumbe, M., Cielo, C. M., de Reuver, S., and 28 others. &lt;strong&gt;Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 25: 100338, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36729053/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;36729053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.gim.2022.11.006&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="36729053">Oskarsdottir et al. (2023)</a> and <a href="#4" class="mim-tip-reference" title="Boot, E., Oskarsdottir, S., Loo, J. C. Y., Crowley, T. B., Orchanian-Cheff, A., Andrade, D. M., Arganbright, J. M., Castelein, R. M., Cserti-Gazdewich, C., de Reuver, S., Fiksinski, A. M., Klingberg, G., and 17 others. &lt;strong&gt;Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.&lt;/strong&gt; Genet. Med. 25: 100344, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36729052/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;36729052&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.gim.2022.11.012&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="36729052">Boot et al. (2023)</a> for clinical practice recommendations for managing children and adults with 22q11.2 deletion syndrome, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=36729052+36729053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>Using a YAC clone containing the VCFS critical region on chromosome 22q11 as a substrate for cDNA selection, <a href="#70" class="mim-tip-reference" title="Sirotkin, H., Morrow, B., DasGupta, R., Goldberg, R., Patanjali, S. R., Shi, G., Cannizzaro, L., Shprintzen, R., Weissman, S. M., Kucherlapati, R. &lt;strong&gt;Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.&lt;/strong&gt; Hum. Molec. Genet. 5: 617-624, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8733128/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8733128&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.5.617&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8733128">Sirotkin et al. (1996)</a> derived a cDNA that encodes a clathrin heavy chain gene (CLTD; <a href="/entry/601273">601273</a>). FISH studies revealed that a cosmid containing the CLTD gene mapped to chromosome 22q11 and was deleted from 2 patients with VCFS who had previously been shown to have deletions of chromosome 22q11. <a href="#70" class="mim-tip-reference" title="Sirotkin, H., Morrow, B., DasGupta, R., Goldberg, R., Patanjali, S. R., Shi, G., Cannizzaro, L., Shprintzen, R., Weissman, S. M., Kucherlapati, R. &lt;strong&gt;Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.&lt;/strong&gt; Hum. Molec. Genet. 5: 617-624, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8733128/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8733128&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.5.617&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8733128">Sirotkin et al. (1996)</a> noted that because VCFS is a complex disorder with significant variability in phenotype and penetrance, it is likely that a number of genes in the commonly deleted region contribute to the phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8733128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#71" class="mim-tip-reference" title="Sirotkin, H., Morrow, B., Saint-Jore, B., Puech, A., Das Gupta, R., Patanjali, S. R., Skoultchi, A., Weissman, S. M., Kucherlapati, R. &lt;strong&gt;Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome.&lt;/strong&gt; Genomics 42: 245-251, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9192844/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9192844&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1997.4734&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9192844">Sirotkin et al. (1997)</a> identified a novel gene, termed transmembrane protein deleted in VCFS (TMVCF; <a href="/entry/602101">602101</a>), in the VCFS critical region. They localized the TMVCF gene between polymorphic markers D22S944 and D22S941, both of which are deleted in more than 80% of VCFS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Carlson, C., Sirotkin, H., Pandita, R., Goldberg, R., McKie, J., Wadey, R., Patanjali, S. R., Weissman, S. M., Anyane-Yeboa, K., Warburton, D., Scambler, P., Shprintzen, R., Kucherlapati, R., Morrow, B. E. &lt;strong&gt;Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.&lt;/strong&gt; Am. J. Hum. Genet. 61: 620-629, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9326327/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9326327&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/515508&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9326327">Carlson et al. (1997)</a> delineated a 480-kb critical region for VCFS, including the genes for GSCL (<a href="/entry/601845">601845</a>), SLC25A1 (<a href="/entry/190315">190315</a>), CLTD, HIRA (<a href="/entry/600237">600237</a>), and TMVCF, as well as a number of novel ordered ESTs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Dunham, I., Collins, J., Wadey, R., Scambler, P. &lt;strong&gt;Possible role for COMT in psychosis associated with velo-cardio-facial syndrome. (Letter)&lt;/strong&gt; Lancet 340: 1361-1362, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1360084/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1360084&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0140-6736(92)92553-r&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1360084">Dunham et al. (1992)</a> pointed out that the HP500 sequence often deleted in VCFS is located within the same 450-kb yeast artificial chromosome (YAC) as the catechol-O-methyltransferase (COMT; <a href="/entry/116790">116790</a>) gene, which might, therefore, be deleted also in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1360084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#52" class="mim-tip-reference" title="Murphy, K. C., Jones, L. A., Owen, M. J. &lt;strong&gt;High rates of schizophrenia in adults with velo-cardio-facial syndrome.&lt;/strong&gt; Arch. Gen. Psychiat. 56: 940-945, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10530637/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10530637&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archpsyc.56.10.940&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10530637">Murphy et al. (1999)</a> examined 50 adults with VCFS using a structured clinical interview to establish a DSM-IV diagnosis. Twelve percent of this sample of 50 patients were referred from a psychiatry clinic; the remainder came from genetics or cardiology. Fifteen individuals with VCFS (30%) had a psychotic disorder, with 12 (24%) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia without VCFS. <a href="#52" class="mim-tip-reference" title="Murphy, K. C., Jones, L. A., Owen, M. J. &lt;strong&gt;High rates of schizophrenia in adults with velo-cardio-facial syndrome.&lt;/strong&gt; Arch. Gen. Psychiat. 56: 940-945, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10530637/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10530637&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archpsyc.56.10.940&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10530637">Murphy et al. (1999)</a> found no evidence that possession of the low-activity COMT allele (val158-to-met; <a href="/entry/116790#0001">116790.0001</a>) was associated with schizophrenia in their sample. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10530637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Baker, K., Baldeweg, T., Sivagnanasundaram, S., Scambler, P., Skuse, D. &lt;strong&gt;COMT val108/158met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome.&lt;/strong&gt; Biol. Psychiat. 58: 23-31, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15935994/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15935994&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.biopsych.2005.03.020&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15935994">Baker et al. (2005)</a> studied 2 hypotheses: first, that individuals with 22q11 deletion syndrome would manifest specific cognitive and neurophysiologic abnormalities in common with individuals at high risk for schizophrenia in the general population; and second, that the COMT val108/158met polymorphism would modify the severity of endophenotypic features. Adolescents and young adults with 22q11 deletion syndrome, aged 13-21, were compared with age- and IQ-matched control subjects on measures that were associated with risk for idiopathic schizophrenia. These individuals displayed poorer verbal working memory and expressive language performance than control subjects. Auditory mismatch negativity event-related potentials were reduced at frontal electrodes but intact at temporal sites. The presence of the COMT val108/158met allele on the single intact chromosome 22 was associated with more marked auditory mismatch negativity amplitude reduction and poorer neuropsychologic performance. Neither allele influenced psychiatric symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15935994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Glaser, B., Debbane, M., Hinard, C., Morris, M. A., Dahoun, S. P., Antonarakis, S. E., Eliez, S. &lt;strong&gt;No evidence for an effect of COMT val158-to-met genotype on executive function in patients with 22q11 deletion syndrome.&lt;/strong&gt; Am. J. Psychiat. 163: 537-539, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16513880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16513880&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1176/appi.ajp.163.3.537&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16513880">Glaser et al. (2006)</a> tested measures of executive function, IQ, and memory in 34 children and young adults with the 22q11.2 deletion syndrome (14 hemizygous for COMT val158 and 30 for met158). No significant differences were detected between met- and val-hemizygous participants on measures of executive function. The groups did not differ on full-scale, performance, and verbal IQ or on verbal and visual memory. <a href="#22" class="mim-tip-reference" title="Glaser, B., Debbane, M., Hinard, C., Morris, M. A., Dahoun, S. P., Antonarakis, S. E., Eliez, S. &lt;strong&gt;No evidence for an effect of COMT val158-to-met genotype on executive function in patients with 22q11 deletion syndrome.&lt;/strong&gt; Am. J. Psychiat. 163: 537-539, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16513880/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16513880&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1176/appi.ajp.163.3.537&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16513880">Glaser et al. (2006)</a> suggested that either the COMT polymorphism has a small effect on executive function in 22q11.2 deletion syndrome or no effect exists at all. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#86" class="mim-tip-reference" title="Yagi, H., Furutani, Y., Hamada, H., Sasaki, T., Asakawa, S., Minoshima, S., Ichida, F., Joo, K., Kimura, M., Imamura, S., Kamatani, N., Momma, K., Takao, A., Nakazawa, M., Shimizu, N., Matsuoka, R. &lt;strong&gt;Role of TBX1 in human del22q11.2 syndrome.&lt;/strong&gt; Lancet 362: 1366-1373, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14585638/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14585638&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(03)14632-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14585638">Yagi et al. (2003)</a> demonstrated mutations in the TBX1 gene in patients with the conotruncal anomaly face syndrome (<a href="/entry/217095">217095</a>)/velocardiofacial syndrome (<a href="/entry/602054#0001">602054.0001</a> and <a href="/entry/602054#0003">602054.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14585638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#55" class="mim-tip-reference" title="Paylor, R., Glaser, B., Mupo, A., Ataliotis, P., Spencer, C., Sobotka, A., Sparks, C., Choi, C.-H., Oghalai, J., Curran, S., Murphy, K. C., Monks, S., Williams, N., O&#x27;Donovan, M. C., Owen, M. J., Scambler, P. J., Lindsay, E. &lt;strong&gt;Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 7729-7734, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16684884/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16684884&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16684884[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0600206103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16684884">Paylor et al. (2006)</a> identified a heterozygous 23-bp deletion in the TBX1 gene (<a href="/entry/602054#0004">602054.0004</a>) in a mother and 2 sons with velocardiofacial syndrome. The mother had major depression (<a href="/entry/608516">608516</a>) and 1 of the sons was diagnosed with Asperger syndrome (see, e.g., <a href="/entry/608638">608638</a> and <a href="/entry/209850">209850</a>). <a href="#55" class="mim-tip-reference" title="Paylor, R., Glaser, B., Mupo, A., Ataliotis, P., Spencer, C., Sobotka, A., Sparks, C., Choi, C.-H., Oghalai, J., Curran, S., Murphy, K. C., Monks, S., Williams, N., O&#x27;Donovan, M. C., Owen, M. J., Scambler, P. J., Lindsay, E. &lt;strong&gt;Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 7729-7734, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16684884/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16684884&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16684884[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0600206103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16684884">Paylor et al. (2006)</a> suggested that the Tbx1 gene is a candidate for psychiatric disease in patients with VCFS and DiGeorge syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16684884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Kaminsky, E. B., Kaul, V., Paschall, J., Church, D. M., Bunke, B., Kunig, D., Moreno-De-Luca, D., Moreno-De-Luca, A., Mulle, J. G., Warren, S. T., Richard, G., Compton, J. G., and 22 others. &lt;strong&gt;An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.&lt;/strong&gt; Genet. Med. 13: 777-784, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21844811/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21844811&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e31822c79f9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21844811">Kaminsky et al. (2011)</a> presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 22q11.2 deletion was identified in 93 cases and no controls for a p value of 9.15 x 10(-21) and a frequency in cases of 1 of 169. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21844811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#46" class="mim-tip-reference" title="McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A., Finucane, B., Driscoll, D. A., Emanuel, B. S., Zackai, E. H. &lt;strong&gt;Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!&lt;/strong&gt; Genet. Med. 3: 23-29, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11339373/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11339373&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00125817-200101000-00006&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11339373">McDonald-McGinn et al. (2001)</a> reported on 30 individuals with the 22q11 deletion that were identified following the diagnosis in a relative. Sixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3- to 4-Mb deletion in most families despite wide inter- and intrafamilial variability, and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="pathogenesis" class="mim-anchor"></a>
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>By analyzing head profile radiographs, <a href="#50" class="mim-tip-reference" title="Molsted, K., Boers, M., Kjar, I. &lt;strong&gt;The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.&lt;/strong&gt; Am. J. Med. Genet. 152A: 1450-1457, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20503320/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20503320&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33381&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20503320">Molsted et al. (2010)</a> found an increased frequency of abnormalities in the morphology of the sella turcica in 33 patients with VCFS, including 30 with either velopharyngeal insufficiency or palatal abnormalities, compared to controls. VCFS patients showed deviations mostly in the posterior part of the dorsum sellae, and patients had increased cranial base angles compared to controls. <a href="#50" class="mim-tip-reference" title="Molsted, K., Boers, M., Kjar, I. &lt;strong&gt;The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.&lt;/strong&gt; Am. J. Med. Genet. 152A: 1450-1457, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20503320/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20503320&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33381&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20503320">Molsted et al. (2010)</a> noted that abnormal morphology of the cranial base and the sella turcica should be considered a cranial malformation. Taking into account that the main features of the disorder are palatal abnormalities, thymic hypoplasia, hypothyroidism, and cardiac defects, the findings of <a href="#50" class="mim-tip-reference" title="Molsted, K., Boers, M., Kjar, I. &lt;strong&gt;The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.&lt;/strong&gt; Am. J. Med. Genet. 152A: 1450-1457, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20503320/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20503320&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33381&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20503320">Molsted et al. (2010)</a> suggested a defect in the neural crest developmental field that includes the thyroid, thymus, and conotruncal septum of the heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20503320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="animalModel" class="mim-anchor"></a>
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#31" class="mim-tip-reference" title="Jerome, L. A., Papaioannou, V. E. &lt;strong&gt;DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.&lt;/strong&gt; Nature Genet. 27: 286-291, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11242110/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11242110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/85845&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11242110">Jerome and Papaioannou (2001)</a> investigated the potential role of the Tbx1 gene (<a href="/entry/602054">602054</a>) in the causation of the DiGeorge/velocardiofacial syndrome (DGS/VCFS) phenotype. This gene, which encodes a transcription factor of the T-box family, maps to 22q11. They produced a null mutation of the Tbx1 gene in mice and found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1 -/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae, and cleft palate. On the basis of this phenotype in mice, <a href="#31" class="mim-tip-reference" title="Jerome, L. A., Papaioannou, V. E. &lt;strong&gt;DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.&lt;/strong&gt; Nature Genet. 27: 286-291, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11242110/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11242110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/85845&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11242110">Jerome and Papaioannou (2001)</a> proposed that TBX1 in humans has a role in the etiology of DGS/VCFS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#49" class="mim-tip-reference" title="Merscher, S., Funke, B., Epstein, J. A., Heyer, J., Puech, A., Lu, M. M., Xavier, R. J., Demay, M. B., Russell, R. G., Factor, S., Tokooya, K., St. Jore, B., and 12 others. &lt;strong&gt;TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.&lt;/strong&gt; Cell 104: 619-629, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11239417/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11239417&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0092-8674(01)00247-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11239417">Merscher et al. (2001)</a> used a Cre-loxP strategy to generate mice that were hemizygous for a 1.5-Mb deletion corresponding to that on 22q11 in VCFS/DGS patients. These mice exhibited significant perinatal lethality and had conotruncal and parathyroid defects. The conotruncal defects could be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 developed conotruncal defects. These results together with the expression patterns of TBX1 suggested a major role for the TBX1 gene in the molecular etiology of VCFS/DGS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Funke, B., Epstein, J. A., Kochilas, L. K., Lu, M. M., Pandita, R. K., Liao, J., Bauerndistel, R., Schuler, T., Schorle, H., Brown, M. C., Adams, J., Morrow, B. E. &lt;strong&gt;Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects.&lt;/strong&gt; Hum. Molec. Genet. 10: 2549-2556, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11709542/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11709542&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.22.2549&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11709542">Funke et al. (2001)</a> reported that mice overexpressing 4 transgenes (PNUTL1, <a href="/entry/602724">602724</a>; GP1BB, <a href="/entry/138720">138720</a>; TBX1; and WDR14, <a href="/entry/610778">610778</a>) had chronic otitis media, a hyperactive circling behavior, and sensorineural hearing loss. This was associated with middle and inner ear malformations analogous to human Mondini dysplasia, reported to occur in VCFS/DGS patients. Based upon its pattern of expression in the ear and functional studies of the gene, the authors hypothesized that Tbx1 likely plays a central role in the etiology of ear defects in these mice, and that haploinsufficiency of TBX1 may be responsible for ear disorders in VCFS/DGS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The CRKL gene (<a href="/entry/602007">602007</a>) encodes an SH2-SH3-SH3 adaptor protein closely related to the Crk (<a href="/entry/164762">164762</a>) gene products. CRKL maps within the common deletion region for DGS/VCFS. <a href="#28" class="mim-tip-reference" title="Guris, D. L., Fantes, J., Tara, D., Druker, B. J., Imamoto, A. &lt;strong&gt;Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.&lt;/strong&gt; Nature Genet. 27: 293-298, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11242111/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11242111&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/85855&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11242111">Guris et al. (2001)</a> reported that mice homozygous for a targeted null mutation at the Crkl locus exhibited defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands, and craniofacial structures. They showed that the migration and early expansion of the neural crest cells is unaffected in Crkl -/- embryos. <a href="#28" class="mim-tip-reference" title="Guris, D. L., Fantes, J., Tara, D., Druker, B. J., Imamoto, A. &lt;strong&gt;Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.&lt;/strong&gt; Nature Genet. 27: 293-298, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11242111/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11242111&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/85855&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11242111">Guris et al. (2001)</a> concluded that the similarity between the Crkl -/- phenotype and the clinical manifestations of DGS/VCFS implicate defects in CRKL-mediated signaling pathways as part of the molecular mechanism underlying this syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#63" class="mim-tip-reference" title="Schinke, M., Izumo, S. &lt;strong&gt;Deconstructing DiGeorge syndrome.&lt;/strong&gt; Nature Genet. 27: 238-240, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11242098/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11242098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/85784&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11242098">Schinke and Izumo (2001)</a> reviewed the genetic structure of the 22q11 region associated with DGS and the syntenic region of mouse chromosome 16. The gene order is inverted between human and mouse in a segment of this region. A table accompanying the figure summarized the phenotypes of mice homozygous or heterozygous mutant for chromosomal deletions or gene mutations of specific regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Df1/+ mice, which model del22q11, present with reduced penetrance of cardiovascular defects similar to those seen in deleted patients but not with other del22q11-like findings. The reduced penetrance of cardiovascular defects is caused by the ability of mutant embryos to recover from a fourth pharyngeal arch artery growth abnormality that is fully penetrant in early embryos. <a href="#74" class="mim-tip-reference" title="Taddei, I., Morishima, M., Huynh, T., Lindsay, E. A. &lt;strong&gt;Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes.&lt;/strong&gt; Proc. Nat. Acad. Sci. 98: 11428-11431, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11562466/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11562466&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11562466[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.201127298&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11562466">Taddei et al. (2001)</a> showed that genetic background has a major effect on the penetrance of cardiovascular defects by affecting this embryonic recovery process. This effect could not be explained by allelic variation at the haploid locus, and is likely to be caused by genetic modifiers elsewhere in the genome. <a href="#74" class="mim-tip-reference" title="Taddei, I., Morishima, M., Huynh, T., Lindsay, E. A. &lt;strong&gt;Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes.&lt;/strong&gt; Proc. Nat. Acad. Sci. 98: 11428-11431, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11562466/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11562466&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11562466[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.201127298&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11562466">Taddei et al. (2001)</a> also showed that genetic factors control extension of the Df1/+ phenotype to include thymic and parathyroid anomalies, establishing the Df1 mouse as a model for the genetic analysis of 3 major features of human del22q11 syndrome. They found that in Df1/+ mice, as in human patients, expression of the heart and thymic phenotypes are essentially independent of each other, suggesting that they may be controlled by different genetic modifiers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11562466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#72" class="mim-tip-reference" title="Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., Kneer, P., von der Ohe, M., Swillen, A., Maes, C., Gewillig, M., Molin, D. G. M., and 20 others. &lt;strong&gt;VEGF: a modifier of the del22q11 (DiGeorge) syndrome?&lt;/strong&gt; Nature Med. 9: 173-182, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12539040/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12539040&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm819&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12539040">Stalmans et al. (2003)</a> reported that absence of the 164-amino acid isoform of Vegf (Vegf164; see <a href="/entry/192240">192240</a>), the only one that binds neuropilin-1 (<a href="/entry/602069">602069</a>), causes birth defects in mice reminiscent of those found in patients with deletion of 22q11. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1 (<a href="/entry/602054">602054</a>), as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down Vegf levels enhanced the pharyngeal arch artery defects induced by Tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a Vegf promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. <a href="#72" class="mim-tip-reference" title="Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., Kneer, P., von der Ohe, M., Swillen, A., Maes, C., Gewillig, M., Molin, D. G. M., and 20 others. &lt;strong&gt;VEGF: a modifier of the del22q11 (DiGeorge) syndrome?&lt;/strong&gt; Nature Med. 9: 173-182, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12539040/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12539040&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nm819&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12539040">Stalmans et al. (2003)</a> concluded that genetic data in mouse, fish, and human indicated that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12539040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Liao, J., Kochilas, L., Nowotschin, S., Arnold, J. S., Aggarwal, V. S., Epstein, J. A., Brown, M. C., Adams, J., Morrow, B. E. &lt;strong&gt;Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage.&lt;/strong&gt; Hum. Molec. Genet. 13: 1577-1585, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15190012/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15190012&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddh176&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15190012">Liao et al. (2004)</a> reported that mice hemizygous for a null allele of Tbx1 had mild malformations, while homozygotes had severe malformations in the affected structures. Neither pattern of malformation precisely modeled VCFS or DGS. Furthermore, bacterial artificial chromosome (BAC) transgenic mice overexpressing human TBX1 and 3 other transgenes had similar malformations to VCFS/DGS patients. By employing genetic complementation studies, the authors demonstrated that altered TBX1 dosage, rather than overexpression of the other transgenes, was responsible for most of the defects in the BAC transgenic mice. Furthermore, the full spectrum of VCFS/DGS malformations was elicited in a TBX1 dose-dependent manner, thus providing a molecular basis for the pathogenesis and varied expressivity of the syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15190012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#69" class="mim-tip-reference" title="Sigurdsson, T., Stark, K. L., Karayiorgou, M., Gogos, J. A., Gordon, J. A. &lt;strong&gt;Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.&lt;/strong&gt; Nature 464: 763-767, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20360742/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20360742&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20360742[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08855&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20360742">Sigurdsson et al. (2010)</a> studied Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22q11.2 that constitutes one of the largest known genetic risk factors for schizophrenia. To examine functional connectivity in these mice, <a href="#69" class="mim-tip-reference" title="Sigurdsson, T., Stark, K. L., Karayiorgou, M., Gogos, J. A., Gordon, J. A. &lt;strong&gt;Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.&lt;/strong&gt; Nature 464: 763-767, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20360742/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20360742&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20360742[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08855&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20360742">Sigurdsson et al. (2010)</a> measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wildtype mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats. Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. <a href="#69" class="mim-tip-reference" title="Sigurdsson, T., Stark, K. L., Karayiorgou, M., Gogos, J. A., Gordon, J. A. &lt;strong&gt;Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.&lt;/strong&gt; Nature 464: 763-767, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20360742/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20360742&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20360742[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08855&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20360742">Sigurdsson et al. (2010)</a> concluded that their data suggested how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level, and further suggested that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20360742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Williams1985" class="mim-tip-reference" title="Williams, M. A., Goldberg, R. B., Shprintzen, R. J. &lt;strong&gt;Male-to-male transmission of the velo-cardio-facial syndrome: a case report and review of 60 cases.&lt;/strong&gt; J. Craniofac. Genet. Dev. Biol. 5: 175-180, 1985.">Williams et al. (1985)</a>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Baker2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Baker, K., Baldeweg, T., Sivagnanasundaram, S., Scambler, P., Skuse, D.
<strong>COMT val108/158met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome.</strong>
Biol. Psychiat. 58: 23-31, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15935994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15935994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15935994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.biopsych.2005.03.020" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Bassett2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., Gatzoulis, M. A.
<strong>Clinical features of 78 adults with 22q11 deletion syndrome.</strong>
Am. J. Med. Genet. 138A: 307-313, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16208694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16208694</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16208694[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16208694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.30984" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Beemer1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Beemer, F. A., de Nef, J. J. E. M., Delleman, J. W., Bleeker-Wagemakers, E. M., Shprintzen, R. J.
<strong>Additional eye findings in a girl with the velo-cardio-facial syndrome. (Letter)</strong>
Am. J. Med. Genet. 24: 541-542, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3089013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3089013</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3089013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320240319" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Boot2023" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Boot, E., Oskarsdottir, S., Loo, J. C. Y., Crowley, T. B., Orchanian-Cheff, A., Andrade, D. M., Arganbright, J. M., Castelein, R. M., Cserti-Gazdewich, C., de Reuver, S., Fiksinski, A. M., Klingberg, G., and 17 others.
<strong>Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.</strong>
Genet. Med. 25: 100344, 2023.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36729052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36729052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36729052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.gim.2022.11.012" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Butcher2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Butcher, N. J., Chow, E. W. C., Costain, G., Karas, D., Ho, A., Bassett, A. S.
<strong>Functional outcomes of adults with 22q11.2 deletion syndrome.</strong>
Genet. Med. 14: 836-843, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22744446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22744446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22744446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/gim.2012.66" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Carelle-Calmels2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., Kuhn, P., Arrive, M., Gilch, C., Schmitt, E., Fehrenbach, S., Schnebelen, A., Frebourg, T., Flori, E.
<strong>Genetic compensation in a human genomic disorder.</strong>
New Eng. J. Med. 360: 1211-1216, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19297573/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19297573</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19297573" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMoa0806544" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Carlson1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Carlson, C., Papolos, D., Pandita, R. K., Faedda, G. L., Veit, S., Goldberg, R., Shprintzen, R., Kucherlapati, R., Morrow, B.
<strong>Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.</strong>
Am. J. Hum. Genet. 60: 851-859, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106531</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Carlson1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Carlson, C., Sirotkin, H., Pandita, R., Goldberg, R., McKie, J., Wadey, R., Patanjali, S. R., Weissman, S. M., Anyane-Yeboa, K., Warburton, D., Scambler, P., Shprintzen, R., Kucherlapati, R., Morrow, B. E.
<strong>Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.</strong>
Am. J. Hum. Genet. 61: 620-629, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326327/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326327</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326327" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/515508" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Conway2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Conway, K., Gibson, R. L., Perkins, J., Cunningham, M. L.
<strong>Pulmonary agenesis: expansion of the VCFS phenotype.</strong>
Am. J. Med. Genet. 113: 89-92, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12400071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12400071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12400071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.10673" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Cunningham2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cunningham, M. L., Perry, R. J., Eby, P. R., Gibson, R. L., Opheim, K. E., Manning, S. C.
<strong>Primary pulmonary dysgenesis in velocardiofacial syndrome: a second patient. (Letter)</strong>
Am. J. Med. Genet. 121A: 177-179, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12910501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12910501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12910501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.20142" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Delio2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Delio, M., Guo, T., McDonald-McGinn, D. M., Zackai, E., Herman, S., Kaminetzky, M., Higgins, A. M., Coleman, K., Chow, C., Jalbrzikowski, M., Bearden, C. E., Bailey, A., and 45 others.
<strong>Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes.</strong>
Am. J. Hum. Genet. 92: 439-447, 2013. Note: Erratum: Am. J. Hum. Genet. 92: 637 only, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23453669/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23453669</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23453669[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23453669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2013.01.018" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Devriendt1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Devriendt, K., Moerman, P., Van Schoubroeck, D., Vandenberghe, K., Fryns, J.-P.
<strong>Chromosome 22q11 deletion presenting as the Potter sequence.</strong>
J. Med. Genet. 34: 423-425, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9152843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9152843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9152843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.5.423" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Digilio2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Digilio, M. C., Marino, B., Cappa, M., Cambiaso, P., Giannotti, A., Dallapiccola, B.
<strong>Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome (deletion 22q11.2 syndrome).</strong>
Genet. Med. 3: 30-33, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11339374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11339374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00125817-200101000-00007" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Driscoll1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Driscoll, D. A., Spinner, N. B., Budarf, M. L., McDonald-McGinn, D. M., Zackai, E. H., Goldberg, R. B., Shprintzen, R. J., Saal, H. M., Zonana, J., Jones, M. C., Mascarello, J. T., Emanuel, B. S.
<strong>Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome.</strong>
Am. J. Med. Genet. 44: 261-268, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1360769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1360769</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1360769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320440237" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Dunham1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dunham, I., Collins, J., Wadey, R., Scambler, P.
<strong>Possible role for COMT in psychosis associated with velo-cardio-facial syndrome. (Letter)</strong>
Lancet 340: 1361-1362, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1360084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1360084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1360084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0140-6736(92)92553-r" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Edelmann1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Edelmann, L., Pandita, R. K., Spiteri, E., Funke, B., Goldberg, R., Palanisamy, N., Chaganti, R. S. K., Magenis, E., Shprintzen, R. J., Morrow, B. E.
<strong>A common molecular basis for rearrangement disorders on chromosome 22q11.</strong>
Hum. Molec. Genet. 8: 1157-1167, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369860/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369860</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369860" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/8.7.1157" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Evers2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Evers, L. J. M., De Die-Smulders, C. E. M., Smeets, E. E. J., Clerkx, M. G. M., Curfs, L. M. G.
<strong>The velo-cardio-facial syndrome: the spectrum of psychiatric problems and cognitive deterioration at adult age.</strong>
Genet. Counsel. 20: 307-315, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20162865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20162865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20162865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Evers2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Evers, L. J. M., Vermaak, M. P., Engelen, J. J. M., Curfs, L. M. G.
<strong>The velocardiofacial syndrome in older age: dementia and autistic features.</strong>
Genet. Counsel. 17: 333-340, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17100202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17100202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17100202" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Fitch1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fitch, N.
<strong>Velo-cardio-facial syndrome and eye abnormality. (Letter)</strong>
Am. J. Med. Genet. 15: 669 only, 1983.
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Forrester2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Forrester, S., Kovach, M. J., Smith, R. E., Rimer, L., Wesson, M.
<strong>Kousseff syndrome caused by deletion of chromosome 22q11-13.</strong>
Am. J. Med. Genet. 112: 338-342, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.10625" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Funke2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Funke, B., Epstein, J. A., Kochilas, L. K., Lu, M. M., Pandita, R. K., Liao, J., Bauerndistel, R., Schuler, T., Schorle, H., Brown, M. C., Adams, J., Morrow, B. E.
<strong>Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects.</strong>
Hum. Molec. Genet. 10: 2549-2556, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709542</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/10.22.2549" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Glaser2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Glaser, B., Debbane, M., Hinard, C., Morris, M. A., Dahoun, S. P., Antonarakis, S. E., Eliez, S.
<strong>No evidence for an effect of COMT val158-to-met genotype on executive function in patients with 22q11 deletion syndrome.</strong>
Am. J. Psychiat. 163: 537-539, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513880</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1176/appi.ajp.163.3.537" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Goldberg1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldberg, R., Motzkin, B., Marion, R., Scambler, P. J., Shprintzen, R. J.
<strong>Velo-cardio-facial syndrome: a review of 120 patients.</strong>
Am. J. Med. Genet. 45: 313-319, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320450307" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Golding-Kushner1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Golding-Kushner, K. J., Weller, G., Shprintzen, R. J.
<strong>Velo-cardio-facial syndrome: language and psychological profiles.</strong>
J. Craniofac. Genet. Dev. Biol. 5: 259-266, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4044789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4044789</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4044789" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Goodman2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goodman, B. K., Rutberg, J., Lin, W. W., Pulver, A. E., Thomas, G. H., Geraghty, M. T.
<strong>Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome.</strong>
J. Inherit. Metab. Dis. 23: 847-848, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11196113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11196113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11196113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/a:1026773005303" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Gothelf2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gothelf, D., Presburger, G., Levy, D., Nahmani, A., Burg, M., Berant, M., Blieden, L. C., Finkelstein, Y., Frisch, A., Apter, A., Weizman, A.
<strong>Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome.</strong>
Am. J. Med. Genet. 126B: 116-121, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15048660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15048660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15048660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.b.20144" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Gothelf2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gothelf, D., Presburger, G., Zohar, A. H., Burg, M., Nahmani, A., Frydman, M., Shohat, M., Inbar, D., Aviram-Goldring, A., Yeshaya, J., Steinberg, T., Finkelstein, Y., Frisch, A., Weizman, A., Apter, A.
<strong>Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.</strong>
Am. J. Med. Genet. 126B: 99-105, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15048657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15048657</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15048657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.b.20124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Guris2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Guris, D. L., Fantes, J., Tara, D., Druker, B. J., Imamoto, A.
<strong>Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.</strong>
Nature Genet. 27: 293-298, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242111</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/85855" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Itsara2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., Mefford, H., Ying, P., Nickerson, D. A., Eichler, E. E.
<strong>Population analysis of large copy number variants and hotspots of human genetic disease.</strong>
Am. J. Hum. Genet. 84: 148-161, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19166990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19166990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19166990[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19166990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2008.12.014" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Jawad2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jawad, A. F., McDonald-McGinn, D. M., Zackai, E., Sullivan, K. E.
<strong>Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).</strong>
J. Pediat. 139: 715-723, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11713452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11713452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11713452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1067/mpd.2001.118534" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Jerome2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jerome, L. A., Papaioannou, V. E.
<strong>DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.</strong>
Nature Genet. 27: 286-291, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/85845" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Kaminsky2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kaminsky, E. B., Kaul, V., Paschall, J., Church, D. M., Bunke, B., Kunig, D., Moreno-De-Luca, D., Moreno-De-Luca, A., Mulle, J. G., Warren, S. T., Richard, G., Compton, J. G., and 22 others.
<strong>An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.</strong>
Genet. Med. 13: 777-784, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21844811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21844811</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21844811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/GIM.0b013e31822c79f9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Karayiorgou1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., Lasseter, V. K., Eisen, H., Childs, B., Kazazian, H. H., Kucherlapati, R., Antonarakis, S. E., Pulver, A. E., Housman, D. E.
<strong>Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.</strong>
Proc. Nat. Acad. Sci. 92: 7612-7616, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7644464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7644464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7644464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.92.17.7612" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Kawame2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kawame, H., Adachi, M., Tachibana, K., Kurosawa, K., Ito, F., Gleason, M. M., Weinzimer, S., Levitt-Katz, L., Sullivan, K., McDonald-McGinn, D. M.
<strong>Graves' disease in patients with 22q11.2 deletion.</strong>
J. Pediat. 139: 892-895, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11743521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11743521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11743521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1067/mpd.2001.119448" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Kelly1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kelly, D., Goldberg, R., Wilson, D., Lindsay, E., Carey, A., Goodship, J., Burn, J., Cross, I., Shprintzen, R. J., Scambler, P. J.
<strong>Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.</strong>
Am. J. Med. Genet. 45: 308-312, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8434616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8434616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320450306" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Kessler-Icekson2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kessler-Icekson, G., Birk, E., Weintraub, A. Y., Barhum, Y., Kotlyar, V., Schlesinger, H., Rockah, R., Vidne, B. A., Frisch, A.
<strong>Association of tetralogy of Fallot with a distinct region of del22q11.2.</strong>
Am. J. Med. Genet. 107: 294-298, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840485" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.10166" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Kirov2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Owen, M. J., O'Donovan, M. C.
<strong>Support for the involvement of large copy number variants in the pathogenesis of schizophrenia.</strong>
Hum. Molec. Genet. 18: 1497-1503, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181681</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19181681[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddp043" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Kok1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kok, L. L., Solman, R. T.
<strong>Velocardiofacial syndrome: learning difficulties and intervention.</strong>
J. Med. Genet. 32: 612-618, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7473652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7473652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7473652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.32.8.612" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Kousseff1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kousseff, B. G.
<strong>Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait.</strong>
Pediatrics 74: 395-398, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6472972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6472972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6472972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Liao2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Liao, J., Kochilas, L., Nowotschin, S., Arnold, J. S., Aggarwal, V. S., Epstein, J. A., Brown, M. C., Adams, J., Morrow, B. E.
<strong>Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage.</strong>
Hum. Molec. Genet. 13: 1577-1585, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15190012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15190012</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15190012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddh176" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Lipson1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lipson, A. H., Yuille, D., Angel, M., Thompson, P. G., Vandervoord, J. G., Beckenham, E. J.
<strong>Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognize.</strong>
J. Med. Genet. 28: 596-604, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1956057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1956057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1956057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.9.596" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Lynch1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lynch, D. R., McDonald-McGinn, D. M., Zackai, E. H., Emanuel, B. S., Driscoll, D. A., Whitaker, L. A., Fischbeck, K. H.
<strong>Cerebellar atrophy in a patient with velocardiofacial syndrome.</strong>
J. Med. Genet. 32: 561-563, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7562973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7562973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7562973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.32.7.561" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Maclean2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maclean, K., Field, M. J., Colley, A. S., Mowat, D. R., Sparrow, D. B., Dunwoodie, S. L., Kirk, E. P. E.
<strong>Kousseff syndrome: a causally heterogeneous disorder.</strong>
Am. J. Med. Genet. 124A: 307-312, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14708106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14708106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14708106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.20418" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Makita1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Makita, Y., Masuno, M., Imaizumi, K., Tachibana, K., Kuroki, Y.
<strong>Idiopathic hypoparathyroidism in two patients with 22q11 microdeletion. (Letter)</strong>
J. Med. Genet. 32: 669, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7473668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7473668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7473668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.32.8.669" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Martin2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Martin, B., Fananas, L., Gutierrez, B., Chow, E. W. C., Bassett, A. S.
<strong>Dermatoglyphic profile in 22q deletion syndrome.</strong>
Am. J. Med. Genet. 128B: 46-49, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15211630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15211630</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15211630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.b.30034" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="McDonald-McGinn2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A., Finucane, B., Driscoll, D. A., Emanuel, B. S., Zackai, E. H.
<strong>Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!</strong>
Genet. Med. 3: 23-29, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11339373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11339373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00125817-200101000-00006" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="McElhinney2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McElhinney, D. B., McDonald-McGinn, D., Zackai, E. H., Goldmuntz, E.
<strong>Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age.</strong>
Pediatrics 108: e104, 2001. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11731631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11731631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1542/peds.108.6.e104" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Meinecke1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Meinecke, P., Beemer, F. A., Schinzel, A., Kushnick, T.
<strong>The velo-cardio-facial (Shprintzen) syndrome: clinical variability in eight patients.</strong>
Europ. J. Pediat. 145: 539-544, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3816857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3816857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3816857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF02429059" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Merscher2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Merscher, S., Funke, B., Epstein, J. A., Heyer, J., Puech, A., Lu, M. M., Xavier, R. J., Demay, M. B., Russell, R. G., Factor, S., Tokooya, K., St. Jore, B., and 12 others.
<strong>TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.</strong>
Cell 104: 619-629, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239417</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0092-8674(01)00247-1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Molsted2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Molsted, K., Boers, M., Kjar, I.
<strong>The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.</strong>
Am. J. Med. Genet. 152A: 1450-1457, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20503320/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20503320</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20503320" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.33381" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Morrow1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morrow, B., Goldberg, R., Carlson, C., Das Gupta, R., Sirotkin, H., Collins, J., Dunham, I., O'Donnell, H., Scambler, P., Shprintzen, R., Kucherlapati, R.
<strong>Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome.</strong>
Am. J. Hum. Genet. 56: 1391-1403, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762562</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Murphy1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Murphy, K. C., Jones, L. A., Owen, M. J.
<strong>High rates of schizophrenia in adults with velo-cardio-facial syndrome.</strong>
Arch. Gen. Psychiat. 56: 940-945, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10530637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10530637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10530637" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archpsyc.56.10.940" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Nickel1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nickel, R. E., Pillers, D.-A. M., Merkens, M., Magenis, R. E., Driscoll, D. A., Emanuel, B. S., Zonana, J.
<strong>Velo-cardial-facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region.</strong>
Am. J. Med. Genet. 52: 445-449, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7747757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7747757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7747757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320520410" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Oskarsdottir2023" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Oskarsdottir, S., Boot, E., Crowley, T. B., Loo, J. C. Y., Arganbright, J. M., Armando, M., Baylis, A. L., Breetvelt, E. J., Castelein, R. M., Chadehumbe, M., Cielo, C. M., de Reuver, S., and 28 others.
<strong>Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.</strong>
Genet. Med. 25: 100338, 2023.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36729053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36729053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36729053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.gim.2022.11.006" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Paylor2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Paylor, R., Glaser, B., Mupo, A., Ataliotis, P., Spencer, C., Sobotka, A., Sparks, C., Choi, C.-H., Oghalai, J., Curran, S., Murphy, K. C., Monks, S., Williams, N., O'Donovan, M. C., Owen, M. J., Scambler, P. J., Lindsay, E.
<strong>Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.</strong>
Proc. Nat. Acad. Sci. 103: 7729-7734, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16684884/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16684884</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16684884[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16684884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.0600206103" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Pulver1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pulver, A. E., Nestadt, G., Goldberg, R., Shprintzen, R. J., Lamacz, M., Wolyniec, P. S., Morrow, B., Karayiogou, M., Antonarakis, S. E., Housman, D., Kucherlapati, R.
<strong>Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.</strong>
J. Nerv. Ment. Dis. 182: 476-478, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8040660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8040660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8040660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00005053-199408000-00010" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="Ruiter2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ruiter, E. M., Bongers, E. M. H. F., Smeets, D. F. C. M., Kuijpers-Jagtman, A. M., Hamel, B. C. J.
<strong>No justification of routine screening for 22q11 deletions in patients with overt cleft palate.</strong>
Clin. Genet. 64: 216-219, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12919136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12919136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12919136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1034/j.1399-0004.2003.00134.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" class="mim-anchor"></a>
<a id="Ryan1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others.
<strong>Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.</strong>
J. Med. Genet. 34: 798-804, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9350810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9350810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9350810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.10.798" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Sahoo2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G.
<strong>Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.</strong>
Genet. Med. 13: 868-880, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21792059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21792059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21792059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/GIM.0b013e3182217a06" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="60" class="mim-anchor"></a>
<a id="Saitta2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saitta, S. C., Harris, S. E., Gaeth, A. P., Driscoll, D. A., McDonald-McGinn, D. M., Maisenbacher, M. K., Yersak, J. M., Chakraborty, P. K., Hacker, A. M., Zackai, E. H., Ashley, T., Emanuel, B. S.
<strong>Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion.</strong>
Hum. Molec. Genet. 13: 417-428, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681306</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14681306[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddh041" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="61" class="mim-anchor"></a>
<a id="Sandrin-Garcia2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sandrin-Garcia, P., Macedo, C., Martelli, L. R., Ramos, E. S., Guion-Almeida, M. L., Richieri-Costa, A., Passos, G. A. S.
<strong>Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome.</strong>
Clin. Genet. 61: 380-383, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12081724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12081724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12081724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1034/j.1399-0004.2002.610511.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="62" class="mim-anchor"></a>
<a id="Scambler1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scambler, P. J., Kelly, D., Lindsay, E., Williamson, R., Goldberg, R., Shprintzen, R., Wilson, D. I., Goodship, J. A., Cross, I. E., Burn, J.
<strong>Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus.</strong>
Lancet 339: 1138-1139, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1349369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0140-6736(92)90734-k" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="63" class="mim-anchor"></a>
<a id="Schinke2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schinke, M., Izumo, S.
<strong>Deconstructing DiGeorge syndrome.</strong>
Nature Genet. 27: 238-240, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/85784" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="64" class="mim-anchor"></a>
<a id="Scire1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scire, G., Dallapiccola, B., Iannetti, P., Bonaiuto, F., Galasso, C., Mingarelli, R., Boscherini, B.
<strong>Hypoparathyroidism as the major manifestation in two patients with 22q11 deletions.</strong>
Am. J. Med. Genet. 52: 478-482, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7747762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7747762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7747762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320520415" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="65" class="mim-anchor"></a>
<a id="Shaikh2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shaikh, T. H., Kurahashi, H., Saitta, S. C., O'Hare, A. M., Hu, P., Roe, B. A., Driscoll, D. A., McDonald-McGinn, D. M., Zackai, E. H., Budarf, M. L., Emanuel, B. S.
<strong>Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.</strong>
Hum. Molec. Genet. 9: 489-501, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10699172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10699172</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10699172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/9.4.489" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="66" class="mim-anchor"></a>
<a id="Shprintzen1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shprintzen, R. J., Goldberg, R. B., Young, D., Wolford, L.
<strong>The velo-cardio-facial syndrome: a clinical and genetic analysis.</strong>
Pediatrics 67: 167-172, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7243439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7243439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7243439" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="67" class="mim-anchor"></a>
<a id="Shprintzen1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shprintzen, R. J., Goldberg, R., Golding-Kushner, K. J., Marion, R.
<strong>Late-onset psychosis in the velo-cardio-facial syndrome.</strong>
Am. J. Med. Genet. 42: 141-142, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1308357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1308357</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1308357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320420131" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="68" class="mim-anchor"></a>
<a id="Shprintzen1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shprintzen, R. J., Wang, F., Goldberg, R., Marion, R.
<strong>The expanded velo-cardio-facial syndrome (VCF): additional features of the most common clefting syndrome. (Abstract)</strong>
Am. J. Hum. Genet. 37: A77, 1985.
</p>
</div>
</li>
<li>
<a id="69" class="mim-anchor"></a>
<a id="Sigurdsson2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sigurdsson, T., Stark, K. L., Karayiorgou, M., Gogos, J. A., Gordon, J. A.
<strong>Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.</strong>
Nature 464: 763-767, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20360742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20360742</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20360742[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20360742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/nature08855" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="70" class="mim-anchor"></a>
<a id="Sirotkin1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sirotkin, H., Morrow, B., DasGupta, R., Goldberg, R., Patanjali, S. R., Shi, G., Cannizzaro, L., Shprintzen, R., Weissman, S. M., Kucherlapati, R.
<strong>Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.</strong>
Hum. Molec. Genet. 5: 617-624, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8733128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8733128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8733128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/5.5.617" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="71" class="mim-anchor"></a>
<a id="Sirotkin1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sirotkin, H., Morrow, B., Saint-Jore, B., Puech, A., Das Gupta, R., Patanjali, S. R., Skoultchi, A., Weissman, S. M., Kucherlapati, R.
<strong>Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome.</strong>
Genomics 42: 245-251, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/geno.1997.4734" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="72" class="mim-anchor"></a>
<a id="Stalmans2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., Kneer, P., von der Ohe, M., Swillen, A., Maes, C., Gewillig, M., Molin, D. G. M., and 20 others.
<strong>VEGF: a modifier of the del22q11 (DiGeorge) syndrome?</strong>
Nature Med. 9: 173-182, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12539040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12539040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12539040" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/nm819" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="73" class="mim-anchor"></a>
<a id="Sundaram2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sundaram, U. T., McDonald-McGinn, D. M., Huff, D., Emanuel, B. S., Zackai, E. H., Driscoll, D. A., Bodurtha, J.
<strong>Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome.</strong>
Am. J. Med. Genet. 143A: 2016-2018, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17676598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17676598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17676598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.31736" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="74" class="mim-anchor"></a>
<a id="Taddei2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Taddei, I., Morishima, M., Huynh, T., Lindsay, E. A.
<strong>Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes.</strong>
Proc. Nat. Acad. Sci. 98: 11428-11431, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11562466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11562466</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11562466[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11562466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.201127298" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="75" class="mim-anchor"></a>
<a id="Toriello1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Toriello, H. V., Sharda, J. K., Beaumont, E. J.
<strong>Autosomal recessive syndrome of sacral and conotruncal developmental field defects (Kousseff syndrome).</strong>
Am. J. Med. Genet. 22: 357-360, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4050868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4050868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4050868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320220220" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="76" class="mim-anchor"></a>
<a id="Tsai1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tsai, C.-H., Van Dyke, D. L., Feldman, G. L.
<strong>A child with velocardiofacial syndrome and del(4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype.</strong>
Am. J. Med. Genet. 82: 336-339, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051168</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="77" class="mim-anchor"></a>
<a id="Van Esch1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van Esch, H., Groenen, P., Fryns, J.-P., Van de Ven, W., Devriendt, K.
<strong>The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome.</strong>
Genet. Counsel. 10: 59-65, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10191430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10191430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10191430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="78" class="mim-anchor"></a>
<a id="Van Geet1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van Geet, C., Devriendt, K., Eyskens, B., Vermylen, J., Hoylaerts, M. F.
<strong>Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets.</strong>
Pediat. Res. 44: 607-611, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9773854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9773854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9773854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-199810000-00023" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="79" class="mim-anchor"></a>
<a id="Van2016" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van, L., Butcher, N. J., Costain, G., Ogura, L., Chow, E. W. C., Bassett, A. S.
<strong>Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome.</strong>
Genet. Med. 18: 350-355, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26087175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26087175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26087175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/gim.2015.84" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="80" class="mim-anchor"></a>
<a id="Vincent1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Vincent, M.-C., Heitz, F., Tricoire, J., Bourrouillou, G., Kuhlein, E., Rolland, M., Calvas, P.
<strong>22q deletion in DGS/VCFS monozygotic twins with discordant phenotypes.</strong>
Genet. Counsel. 10: 43-49, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10191428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10191428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10191428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="81" class="mim-anchor"></a>
<a id="Williams1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Williams, M. A., Goldberg, R. B., Shprintzen, R. J.
<strong>Male-to-male transmission of the velo-cardio-facial syndrome: a case report and review of 60 cases.</strong>
J. Craniofac. Genet. Dev. Biol. 5: 175-180, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4019731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4019731</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4019731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="82" class="mim-anchor"></a>
<a id="Williams1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Williams, M. A., Shprintzen, R. J., Rakoff, S. J.
<strong>Adenoid hypoplasia in the velo-cardio-facial syndrome.</strong>
J. Craniofac. Genet. Dev. Biol. 7: 23-26, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3597719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3597719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3597719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="83" class="mim-anchor"></a>
<a id="Woodin2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Woodin, M., Wang, P. P., Aleman, D., McDonald-McGinn, D., Zackai, E., Moss, E.
<strong>Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion.</strong>
Genet. Med. 3: 34-39, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11339375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11339375</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11339375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00125817-200101000-00008" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="84" class="mim-anchor"></a>
<a id="Worthington1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Worthington, S., Colley, A., Fagan, K., Dai, K., Lipson, A. H.
<strong>Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?</strong>
J. Med. Genet. 34: 79-82, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9032655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9032655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9032655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.1.79" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="85" class="mim-anchor"></a>
<a id="Wraith1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wraith, J. E., Super, M., Watson, G. H., Phillips, M.
<strong>Velo-cardio-facial syndrome presenting as holoprosencephaly.</strong>
Clin. Genet. 27: 408-410, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3995791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3995791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3995791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1985.tb02284.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="86" class="mim-anchor"></a>
<a id="Yagi2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yagi, H., Furutani, Y., Hamada, H., Sasaki, T., Asakawa, S., Minoshima, S., Ichida, F., Joo, K., Kimura, M., Imamura, S., Kamatani, N., Momma, K., Takao, A., Nakazawa, M., Shimizu, N., Matsuoka, R.
<strong>Role of TBX1 in human del22q11.2 syndrome.</strong>
Lancet 362: 1366-1373, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14585638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14585638</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14585638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(03)14632-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 06/04/2020
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 05/06/2019<br>Ada Hamosh - updated : 10/14/2013<br>Ada Hamosh - updated : 11/7/2012<br>Ada Hamosh - updated : 10/4/2012<br>Ada Hamosh - updated : 12/14/2011<br>Cassandra L. Kniffin - updated : 11/29/2010<br>Ada Hamosh - updated : 4/28/2010<br>Cassandra L. Kniffin - updated : 3/10/2010<br>Ada Hamosh - updated : 7/28/2009<br>Kelly A. Przylepa - updated : 10/25/2007<br>Cassandra L. Kniffin - updated : 3/13/2007<br>John Logan Black, III - updated : 1/23/2007<br>George E. Tiller - updated : 1/16/2007<br>Cassandra L. Kniffin - updated : 12/7/2006<br>George E. Tiller - updated : 12/4/2006<br>Marla J. F. O'Neill - updated : 7/26/2006<br>Cassandra L. Kniffin - updated : 6/1/2006<br>John Logan Black, III - updated : 5/17/2006<br>Cassandra L. Kniffin - updated : 3/9/2006<br>John Logan Black, III - updated : 12/21/2005<br>Cassandra L. Kniffin - updated : 10/5/2005<br>Victor A. McKusick - updated : 12/23/2003<br>Victor A. McKusick - updated : 10/16/2003<br>Deborah L. Stone - updated : 5/29/2003<br>Ada Hamosh - updated : 2/27/2003<br>Victor A. McKusick - updated : 11/7/2002<br>Victor A. McKusick - updated : 9/16/2002<br>Deborah L. Stone - updated : 9/11/2002<br>George E. Tiller - updated : 5/9/2002<br>Ada Hamosh - updated : 4/30/2002<br>Sonja A. Rasmussen - updated : 3/7/2002<br>Ada Hamosh - updated : 2/13/2002<br>Ada Hamosh - updated : 1/29/2002<br>Ada Hamosh - updated : 1/9/2002<br>Victor A. McKusick - updated : 11/1/2001<br>Stylianos E. Antonarakis - updated : 3/6/2001<br>Ada Hamosh - updated : 2/6/2001<br>George E. Tiller - updated : 4/14/2000<br>Victor A. McKusick - updated : 1/14/2000<br>Wilson H. Y. Lo - updated : 9/22/1999<br>Wilson H. Y. Lo - updated : 8/12/1999<br>Wilson H. Y. Lo - updated : 8/12/1999<br>Sonja A. Rasmussen - updated : 5/12/1999<br>Victor A. McKusick - updated : 2/24/1999<br>Michael J. Wright - updated : 6/5/1998<br>Jennifer P. Macke - updated : 11/26/1997<br>Michael J. Wright - updated : 11/20/1997<br>Victor A. McKusick - updated : 6/12/1997<br>Moyra Smith - Updated : 5/22/1996
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/2/1986
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 11/19/2024
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 11/12/2020<br>alopez : 06/04/2020<br>carol : 02/13/2020<br>carol : 07/19/2019<br>alopez : 05/06/2019<br>alopez : 06/26/2018<br>carol : 03/03/2017<br>carol : 01/08/2016<br>carol : 1/7/2016<br>carol : 3/21/2014<br>alopez : 10/14/2013<br>alopez : 10/14/2013<br>alopez : 11/8/2012<br>terry : 11/7/2012<br>alopez : 10/4/2012<br>alopez : 1/4/2012<br>terry : 12/14/2011<br>alopez : 5/11/2011<br>wwang : 12/1/2010<br>ckniffin : 11/29/2010<br>carol : 7/1/2010<br>alopez : 4/29/2010<br>terry : 4/28/2010<br>wwang : 3/19/2010<br>ckniffin : 3/10/2010<br>ckniffin : 3/10/2010<br>carol : 8/13/2009<br>terry : 7/28/2009<br>alopez : 6/10/2009<br>terry : 5/19/2009<br>carol : 12/1/2008<br>terry : 9/26/2008<br>alopez : 2/28/2008<br>carol : 10/25/2007<br>wwang : 3/13/2007<br>carol : 1/23/2007<br>alopez : 1/17/2007<br>alopez : 1/17/2007<br>terry : 1/16/2007<br>wwang : 12/7/2006<br>wwang : 12/5/2006<br>terry : 12/4/2006<br>wwang : 9/18/2006<br>wwang : 8/1/2006<br>terry : 7/26/2006<br>wwang : 6/14/2006<br>ckniffin : 6/1/2006<br>wwang : 5/23/2006<br>terry : 5/17/2006<br>wwang : 3/16/2006<br>ckniffin : 3/9/2006<br>terry : 12/23/2005<br>carol : 12/21/2005<br>wwang : 10/12/2005<br>ckniffin : 10/5/2005<br>terry : 2/22/2005<br>carol : 2/12/2004<br>terry : 12/23/2003<br>cwells : 10/21/2003<br>terry : 10/16/2003<br>carol : 6/24/2003<br>carol : 5/29/2003<br>alopez : 3/4/2003<br>terry : 2/27/2003<br>mgross : 12/10/2002<br>tkritzer : 11/13/2002<br>terry : 11/7/2002<br>terry : 11/7/2002<br>carol : 9/16/2002<br>carol : 9/11/2002<br>cwells : 5/17/2002<br>cwells : 5/9/2002<br>alopez : 5/1/2002<br>terry : 4/30/2002<br>carol : 4/8/2002<br>carol : 3/8/2002<br>terry : 3/7/2002<br>alopez : 2/14/2002<br>terry : 2/13/2002<br>alopez : 1/31/2002<br>terry : 1/29/2002<br>alopez : 1/17/2002<br>terry : 1/9/2002<br>mcapotos : 11/20/2001<br>mcapotos : 11/9/2001<br>terry : 11/1/2001<br>carol : 9/13/2001<br>mgross : 3/6/2001<br>mgross : 3/6/2001<br>alopez : 2/26/2001<br>alopez : 2/22/2001<br>mcapotos : 2/12/2001<br>mcapotos : 2/9/2001<br>terry : 2/6/2001<br>alopez : 4/14/2000<br>terry : 4/14/2000<br>carol : 2/1/2000<br>terry : 1/14/2000<br>carol : 12/13/1999<br>carol : 9/22/1999<br>carol : 8/12/1999<br>carol : 8/12/1999<br>carol : 5/12/1999<br>carol : 5/12/1999<br>terry : 2/24/1999<br>terry : 7/29/1998<br>alopez : 6/17/1998<br>terry : 6/5/1998<br>carol : 5/8/1998<br>alopez : 12/5/1997<br>alopez : 12/3/1997<br>alopez : 12/3/1997<br>dholmes : 11/26/1997<br>dholmes : 11/26/1997<br>mark : 7/8/1997<br>mark : 6/16/1997<br>terry : 6/12/1997<br>carol : 5/22/1996<br>carol : 5/18/1996<br>mark : 12/11/1995<br>mark : 10/9/1995<br>mimadm : 6/7/1995<br>terry : 5/25/1995<br>carol : 4/11/1994<br>carol : 2/19/1993<br>carol : 1/19/1993
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 192430
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
VELOCARDIOFACIAL SYNDROME; VCFS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CHROMOSOME 22q11.2 DELETION SYNDROME<br />
VCF SYNDROME<br />
SHPRINTZEN VCF SYNDROME
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>ICD10CM:</strong> Q93.81; &nbsp;
<strong>ICD9CM:</strong> 758.32; &nbsp;
<strong>ORPHA:</strong> 567; &nbsp;
<strong>DO:</strong> 12583; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
22q11.21
</span>
</td>
<td>
<span class="mim-font">
Velocardiofacial syndrome
</span>
</td>
<td>
<span class="mim-font">
192430
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
TBX1
</span>
</td>
<td>
<span class="mim-font">
602054
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because the velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS; 188400) are caused by a 1.5- to 3.0-Mb hemizygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the syndrome in most patients.</p><p>Shprintzen et al. (1981) reported on 39 patients with a syndrome characterized by the following frequent features: cleft palate, cardiac anomalies, typical facies, and learning disabilities. Less frequent features included microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, and inguinal hernia. The Pierre Robin syndrome was present in 4. The heart malformation was most often ventricular septal defect. In the group studied, mother and daughter were affected in 2 instances, mother and son in 1, and mother and both daughter and son in 1. </p><p>Fitch (1983) found small optic discs with tortuous vessels in an affected 6-year-old girl, the offspring of first-cousin parents.</p><p>Wraith et al. (1985) reported a male infant with holoprosencephaly and tetralogy of Fallot with death at 32 days. The mother had the same heart lesion, tetralogy of Fallot (totally corrected by surgery at age 12 years), and a large submucous cleft palate causing nasal voice. Her face was considered typical of VCF syndrome: prominent tubular nose, narrow palpebral fissures, and slightly retruded mandible. She was mildly retarded. Another child, female, may have been affected. The authors suggested that the association of tetralogy of Fallot and prosencephaly should prompt search for signs of VCF syndrome in relatives. </p><p>Shprintzen et al. (1985) claimed that VCFS is the most frequent clefting syndrome, accounting for 8.1% of children with palatal clefts seen in their center. Learning disabilities characterized by difficulty with abstraction, reading comprehension, and mathematics is found in all cases as is a characteristic facial dysmorphia. Cardiac anomalies were found in 82%. Platybasia occurred in 85%. Ophthalmologic abnormalities, including tortuous retinal vessels, small optic discs, posterior embryotoxon, or bilateral cataracts, were observed in 70%. Neonatal hypocalcemia requiring treatment occurred in almost 13%. Small or absent lymphoid tissue was documented by nasopharyngoscopic examination in a great majority. Most patients had frequent infections, and T-lymphocyte dysfunction was found. Male-to-male transmission established autosomal dominant inheritance.</p><p>Marked tortuosity of the retinal vessels, as noted in earlier reports, was commented on by Beemer et al. (1986). </p><p>Meinecke et al. (1986) reported 8 patients with the VCF syndrome; 3 cases were sporadic and 5 others occurred in 2 families. The authors concluded that the frequency of cardiovascular anomalies and cleft palate has been incorrectly estimated to be high, 98% and 82%, respectively, because patients have been ascertained in cardiac or cleft palate clinics. Their 8 patients were diagnosed mainly through their pattern of facial dysmorphism and only 2 and 4 of the 8, respectively, had clefts and heart defects. Furthermore, mental retardation, noted in all cases in previous publications, was not present in any of these 8 patients. They suspected that the rate of fresh mutations may not be as high as previously assumed because of mild expression in some family members. </p><p>Williams et al. (1987) found evidence for congenital hypoplasia of the adenoids in over four-fifths of patients with the VCF syndrome. They suggested that this feature contributes to the hypernasal speech found in persons with this condition because normally velopharyngeal closure during speech is aided by the adenoids. </p><p>Lipson et al. (1991) reported on 38 cases including 2 familial cases. They emphasized the frequent delay in diagnosis and treatment for the hypernasal speech and velopharyngeal insufficiency. Overt cleft palate was present in 7 of the cases and submucous cleft in 15. Congenital heart disease was present in 16. Velopharyngeal insufficiency was present in all but one; pharyngoplasty was performed in all but 6 of the cases and results were good in all of these. Lipson et al. (1991) published photographs illustrating the main facial features: almond-shaped palpebral fissures, deficient nasal alae, bulbous nasal tip in older children, myopathic facies, and small open mouth. Hypernasal speech was often the finding that brought the children to attention. </p><p>Goldberg et al. (1993) reviewed the full spectrum of the velocardiofacial syndrome on the basis of 120 patients. Learning disability, cleft palate, and pharyngeal hypotonia were present in 90% or more of the patients; cardiac anomalies in 82%; slender hands and digits in 63%; medial displacement of internal carotid arteries in 25%; umbilical hernia in 23%; and hypospadias in 10% of males. </p><p>Nickel et al. (1994) reported 3 patients with meningomyelocele, congenital heart defects, and 22q11 deletions. Two of the children had the clinical diagnosis of VCFS; both also had bifid uvula. The third child had DiGeorge sequence. </p><p>Scire et al. (1994) reported clinical features of 2 adolescent males illustrating that the main manifestation of 22q11 deletion can be chronic symptomatic hypocalcemia secondary to hypoparathyroidism, together with seizures and cerebral calcifications. The patients had no cardiac abnormality or T-cell deficiency and had no cleft palate, features that occur in the DiGeorge syndrome (188400) and VCFS. The patients did have facial features of VCFS, and one in particular had a hypernasal voice. </p><p>Makita et al. (1995) reported 2 further cases of isolated hypoparathyroidism in whom they demonstrated a 22q11 deletion by fluorescence in situ hybridization. </p><p>Kousseff (1984) described 3 sibs with a syndrome of sacral meningocele, conotruncal cardiac defects, unilateral renal agenesis (in 1 sib), low-set and posteriorly angulated ears, retrognathia, and short neck with low posterior hairline. Kousseff (1984) suggested autosomal recessive inheritance. Toriello et al. (1985) reported a similar, isolated case and designated the disorder Kousseff syndrome. Forrester et al. (2002) restudied the family reported by Kousseff (1984) and identified a 22q11-q13 deletion in the proband, his deceased brother, and his father. The proband had spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velocardiofacial syndrome, including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. His brother had died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and his sister had died at 22 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly. </p><p>Maclean et al. (2004) reported 2 patients with Kousseff syndrome, 1 with a 22q11.2 deletion and the other without. The first was a 4-year-old girl with a sacral myelomeningocele, tetralogy of Fallot, microcephaly, hydrocephalus, hypoplasia of the corpus callosum, and moderate developmental delay, who had a normal chromosome 22q11.2 FISH test and did not exhibit the facial phenotype of VCFS. The second patient, a male infant who died at 10 days of age, had a large sacral myelomeningocele, hydrocephalus, Arnold-Chiari malformation, atrial septal defect, conoventricular ventricular septal defect, type B interrupted aortic arch, hypocalcemia, and suspected duodenal stenosis; FISH testing revealed a 22q11.2 microdeletion. Maclean et al. (2004) concluded that Kousseff syndrome is a distinct clinical entity that is genetically heterogeneous. </p><p>Lynch et al. (1995) reported the case of a 34-year-old man who presented for neurologic evaluation for cerebellar atrophy of unknown etiology. By history, he had had neonatal hypocalcemia, an atrial septal defect, and a corrected cleft palate. Physical examination showed the characteristic facies of velocardiofacial syndrome, as well as dysmetria and dysdiadochokinesia consistent with cerebellar degeneration. An MRI scan of his head performed by the authors showed vermian and hemispheric cerebellar atrophy, calcification of the basal ganglia, a small brainstem without focal loss of volume, and multiple white matter lucencies on T2-weighted images. The white matter lesions were suggestive of axonal loss, ischemia, or demyelination. Molecular cytogenetic studies showed a deletion of 22q11.2, del(22)(q11.21-q11.23). This case represented the first report of the association of a neurodegenerative disorder with velocardiofacial syndrome or DiGeorge syndrome. </p><p>Ryan et al. (1997) reported a European collaborative study of 558 patients with deletions of 22q11. In 204 of the 285 patients for whom parental deletion status was available, neither parent had the deletion. Of the 81 inherited deletions, the sex of the parent with the deletion was known in 79 cases, with 61 maternal and 18 paternal deletions. Growth data were available for 131 of 158 patients whose heights and/or weights were less than the 50th centile; 57 of 158 were below the 3rd centile for either height or weight. Forty-four patients had died, and of the 29 for whom age of death was available, 16 had died within 1 month and 25 within 6 months as a consequence of congenital heart disease. There was 1 death from severe immune deficiency. A total of 107 of 338 cases were developmentally normal, although 37 of these had speech delay. Of 231 patients with abnormal development, 102 had mild delay and 60 had either moderate or severe learning difficulties. Twenty-two of 252 children in the study had behavioral or psychiatric problems, including 2 with episodes of psychosis; 11 of 61 adults had a psychiatric disorder, 4 of whom had had at least 1 episode of psychosis. Cardiac studies were recorded in 545 patients, of whom 409 had significant cardiac pathology, most commonly tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, pulmonary atresia/ventricular septal defect, and truncus arteriosus. A total of 242 of 496 patients had otolaryngeal abnormalities, with 72 having either an overt cleft palate or submucous cleft; 161 patients had velopharyngeal insufficiency without clefting. Of 159 patients in whom data on hearing were available, 52 had abnormal hearing, with data on the type of hearing loss available in only 17, in all of whom this was conductive in type. A total of 49 of 136 patients had renal abnormalities, with absent, dysplastic, or multicystic kidneys in 23, obstructive abnormalities in 14, and vesicoureteric reflux in 6. A total of 203 of 340 had recorded hypocalcemia; 108 of this group had a history of seizures, and 42 of these had had seizures secondary to hypocalcemia. Most hypocalcemia was reported in the neonatal period, but 1 patient presented at 18 years of age. Laboratory and clinical immune function and thymus status were available in 218 patients. Only 4 of these were classified as having a major immune function abnormality. Two of these had died, with severe immunodeficiency being the cause of death in 1. A total of 94 of 548 patients had minor abnormalities of the skeletal system, and 39 of 548 had ocular anomalies. Ten offspring comparisons showed that 27 of 35 children had more severe congenital heart disease than their parents, with 8 of 35 having the same degree of severity. Developmental status was worse in 9 of 17 and the same in 7 of 17. Palatal abnormalities were better in 10 of 22 children and similar to the parents in 12 of 22 children. Sibship comparisons in 26 sibs from 12 families showed considerable variation in heart abnormalities between sibs, and development status was similar in most cases. Ryan et al. (1997) concluded that most of the clinical findings in their study reflected previous reports; however, fewer immunologic problems and more renal problems than were expected were found. Ryan et al. (1997) therefore recommended that abdominal ultrasound be carried out in all patients with 22q11 deletions. They also recommended that both parents be studied when a child is found to have a deletion. </p><p>Vincent et al. (1999) reported the case of female monozygotic twins with 22q11 deletions. The twins shared facial characteristics of DGS/VCFS and immunologic defect. However, only one, who died on day 5, had a cardiac defect, composed of an interrupted aortic arch with a ventricular septal defect, a truncus arteriosus, and a large arterial duct. The authors stated that this was the fourth report of a discrepant cardiac status between monozygotic twins harboring 22q11 deletions. </p><p>Worthington et al. (1997) reported 3 cases of VCFS with anal anomalies (2 cases of anal stenosis and one of a covered anus with a perineal fistula) and confirmed deletions of the 22q11 region by FISH. They presented an additional case of a child with clinical VCFS whose father was born with an imperforate anus and had mental retardation presumably because of VCFS; this family had been lost to follow-up. </p><p>Devriendt et al. (1997) reported a female fetus with Potter sequence caused by unilateral renal agenesis and contralateral multicystic renal dysplasia. Additionally, there was agenesis of the uterus and oviducts (Von Mayer-Rokitansky-Kuster anomaly). The father had dysmorphic features typical of VCFS, and fluorescence in situ hybridization analysis confirmed deletions of chromosome 22q11 in both father and fetus. The fetus had no dysmorphic features suggestive of VCFS and no cardiovascular abnormalities. </p><p>Sundaram et al. (2007) described 2 patients with 22q11.2 deletion who had absent uterus and unilateral renal agenesis. One patient also had mild developmental delay, hypoparathyroidism, and psychiatric symptoms; the other patient also had high-arched palate, bulbous nasal tip, bicuspid aortic valve, short stature, and primary amenorrhea. Sundaram et al. (2007) suggested that mullerian or uterine/vaginal agenesis be included as part of the clinical spectrum of 22q11.2 deletion syndrome. </p><p>Van Geet et al. (1998) studied a family in which all 3 members with a 22q11 microdeletion and VCFS had giant platelets and a mild decrease in platelet number. Platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. They studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Since patients with 22q11 deletion are expected to be heterozygous for deletion of the GP1BB gene (138720), they can be considered to be carriers of the Bernard-Soulier syndrome (231200). A significant increase in platelet size may be a positive predictor for the clinical diagnosis of VCFS. </p><p>Digilio et al. (2001) reported on the growth parameters of 73 patients with the 22q11 deletion. In general, these patients were characterized by weight deficiency in the first years of life, weight normalization in the following years, development of obesity in adolescence, short stature in 10% of the patients, normal height in adolescents, slight delay in bone age in infancy, and microcephaly in 10% of the patients. </p><p>Jawad et al. (2001) studied 195 patients with chromosome 22q11.2 deletion syndrome and found that diminished T-cell counts in the peripheral blood are common. The pattern of changes seen with aging in normal control patients was also seen in patients with the chromosome 22q11.2 deletion syndrome, although the decline in T cells was blunted. Autoimmune disease was seen in most age groups, although the types of disorders varied according to age. Infections were also common in older patients, although they were seldom life-threatening. Juvenile rheumatoid arthritis with onset between 1.5 and 6 years of age was seen in 4 of the 195 patients; idiopathic thrombocytopenia purpura with onset at 1 to 8 years of age was seen in 8 of 195 patients; autoimmune hemolytic anemia, psoriasis, vitiligo, inflammatory bowel disease, adult rheumatoid arthritis, and rheumatic fever with chorea were each seen in 1 patient of the 195 patients sampled. </p><p>Kawame et al. (2001) reported 5 patients with chromosome 22q11.2 deletion that manifested Graves disease between the ages of 27 months and 16 years, and suggested that Graves disease may be part of the clinical spectrum of this disorder. </p><p>McElhinney et al. (2001) studied 29 patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age to determine the incidence of cardiovascular anomalies. In 11 of 29 (38%) patients, cardiovascular anomalies were detected, including 3 with a vascular ring, 3 with a right aortic arch with mirror-image branching of the brachiocephalic arteries (no vascular ring; one with a patent ductus arteriosus; see 607411), and 4 with a left aortic arch with an aberrant right subclavian artery (no vascular ring; 1 with a patent ductus), and 1 with a left superior vena cava draining to the coronary sinus. All 3 patients with vascular rings and 1 with a patent ductus arteriosus required intervention, giving an incidence of 14% in this study. </p><p>Kessler-Icekson et al. (2002) examined myocardial tissues removed after corrective surgery of 31 patients with congenital heart defects (21 with tetralogy of Fallot and 10 with a double-chamber right ventricle) using a set of 9 polymorphic short tandem repeat markers along the 22q11.2 region. Ten (48%) of the tetralogy of Fallot patients had homozygosity for 3 or more consecutive markers, suggesting possible 22q11.2 deletions. None of the patients with double-chamber right ventricle had this finding. </p><p>Martin et al. (2004) identified an altered dermatoglyphic profile in 22q deletion syndrome patients, which involved (1) ATD angle and amplitude, (2) the presence of radial loops in the hypothenar area, and (3) fluctuating asymmetry. Martin et al. (2004) noted that the first 2 features are similar to those found in other genetic syndromes associated with low IQ, whereas high levels of fluctuating asymmetry have often been reported in schizophrenia. </p><p>Sandrin-Garcia et al. (2002) described a family in which a patient had the clinical diagnosis of VCFS and his sister had a suggestive phenotype. Both were found to carry a deletion in 22q11.2 of maternal origin. The mother and other unaffected relatives did not show the deletion, suggesting that the mother had gonadal mosaicism with a normal DNA profile in the blood cells. </p><p>Conway et al. (2002) described a child with the typical craniofacial manifestations of VCFS and unilateral pulmonary agenesis. They suggested that the patient's pulmonary agenesis was related to a disruption of the dorsal aortic arch development that selectively interfered with lung bud growth and, further, that pulmonary agenesis should be considered part of the spectrum of malformations seen in 22q11.2 deletion. Cunningham et al. (2003) reported a second patient with VCFS, confirmed by genetic detection of 22q11.2 deletion, and unilateral primary pulmonary agenesis. High-resolution CT imaging showed a hypoplastic left lung comprising a single lobe, small left bronchus, hypoplastic left pulmonary artery, and hypoplastic left chest wall with complete shift of the trachea and mediastinum into the left hemithorax. The patient also had congenital conductive hearing loss due to malformation and subluxation of the left stapes, and hypoplasia of the left mandible. </p><p>Bassett et al. (2005) described the phenotypic features of 78 adults with 22q11 deletion syndrome and identified 43 distinct features present in more than 5% of patients. Common characteristic features included intellectual disabilities (92.3%), hypocalcemia (64%), palatal anomalies (42%), and cardiovascular anomalies (25.8%). Other less commonly appreciated features included obesity (35%), hypothyroidism (20.5%), hearing deficits (28%), cholelithiasis (19%), scoliosis (47%), and dermatologic abnormalities (severe acne, 23%; seborrhea, 35%). Significantly, schizophrenia was present in 22.6% of patients. </p><p><strong><em>Neuropsychologic Features</em></strong></p><p>
Golding-Kushner et al. (1985) observed that children with VCFS had 'characteristic personality features,' which were described as blunt or inappropriate affect, and that a greater than expected number of these children developed severe psychiatric illnesses as they approached adolescence. </p><p>Shprintzen et al. (1992) pointed out that psychotic illness is a feature of VCFS in adolescents or adults. In a pilot study of patients diagnosed with VCFS and their relatives, Pulver et al. (1994) found a high rate of psychosis among the patients and their relatives, suggesting that there may be a gene associated with schizophrenia (see 181500) on chromosome 22q or that a DNA rearrangement in this region may be important to the etiology of some forms of schizophrenia. </p><p>Kok and Solman (1995) emphasized the usefulness of interactive computer-based instruction for the development of reading, language, spelling, and numeracy skills in VCFS individuals. </p><p>Woodin et al. (2001) reported updated findings of neuropsychologic data from 80 children with the 22q11 deletion. The subjects showed higher verbal than nonverbal IQ scores, assets in verbal memory, and deficits in the areas of attention, story memory, visuospatial memory, arithmetic performance relative to other areas of achievement, and psychosocial functioning. </p><p>Gothelf et al. (2004) studied 43 patients with VCFS for obsessive-compulsive symptoms, using the Yale-Brown obsessive compulsive scale and a semistructured psychiatric interview. Fourteen of the subjects (32.6%) met DSM-IV criteria for obsessive-compulsive disorder (OCD; see 164230); in these patients, the symptoms began at an early age and generally responded to fluoxetine treatment. Additionally, 16 of the patients (37.2%) had attention-deficit hyperactivity disorder (ADHD; see 143465) and 7 (16.2%) had a psychotic disorder. </p><p>Gothelf et al. (2004) investigated the association of familial, developmental, and physical factors with the occurrence of ADHD in 51 patients with nonfamilial VCFS. Twenty-one patients (41.2%) were diagnosed with ADHD. There was a significantly greater prevalence of ADHD in the first-degree relatives of patients with ADHD than in those without (odds ratio, 5.9, 95% CI, 1.6-22.1; p = 0.006). ADHD and non-ADHD groups had similar IQ scores (total, verbal, and performance) and had a similar average degree of severity of facial dysmorphism and cardiac and cleft anomalies. Gothelf et al. (2004) suggested that there is a genetic contribution to ADHD in VCFS. </p><p>Evers et al. (2006) reported a 52-year-old man with 22q11.2 deletion. As a child he showed learning disabilities and behavioral problems. As a young adult, he exhibited aggressive outbursts, apathy, echolalia, perseverations, and psychotic features, including delusional thoughts and hallucinations, necessitating long-term care in a psychiatric facility. Since then, he has demonstrated aggressive behavior, periods of withdrawal, and progressive cognitive decline consistent with dementia, particularly since the age of 36 years. An affected autistic sister also had the deletion. </p><p>Evers et al. (2009) reported 7 unrelated adult patients with the 22q11.2 deletion and low cognitive function. Most had psychotic episodes in their young adult lives followed by intellectual decline. Other variable features included paranoia, aggression, mood swings, destructive behavior, autistic disorder, and dementia. At the time of the report, all were living in long-term residential care. All presented with intellectual disability, which later developed into more severe psychiatric illnesses, leading to the correct molecular diagnosis later in life. </p><p>Butcher et al. (2012) used the Vineland Adaptive Behavior Scales to assess functioning in 100 adults with 22q11.2 deletion syndrome (46 males; mean age = 28.8 (SD = 9.7) years) where intellect ranged from average to borderline (57 individuals) to mild intellectual disability (43 individuals). More than 75% of the subjects scored in the functional deficit range. Although personal, vocational, and financial demographics confirmed widespread functional impairment, daily living skills and employment were relative strengths. Intelligence quotient was a significant predictor (p less than 0.001) of overall and domain-specific adaptive functioning skills. A diagnosis of schizophrenia was a significant predictor (p less than 0.05) of overall adaptive functioning, daily living skills, and socialization scores. Notably, congenital heart disease, history of mood/anxiety disorders, sex, and age were not significant predictors of functioning. Butcher et al. (2012) concluded that, despite functional impairment in adulthood that is primarily mediated by cognitive and psychiatric phenotypes, relative strengths in activities of daily living and employment have important implications for services and long-term planning in patients with 22q11.2 deletion syndrome. </p><p>Van et al. (2016) investigated the relationship of small for gestational age (SGA) birth weight (less than 3rd percentile for sex and gestational age) and prematurity (less than 37 weeks' gestation) to expression of schizophrenia in a well-characterized cohort of 123 adults with 22q11 deletion syndrome. SGA birth weight (OR = 3.52, 95% CI 1.34-9.22) and prematurity (OR = 5.38, 95% CI = 1.63-17.75), but not maternal factors, were significant risk factors for schizophrenia in 22q11.2 deletion syndrome. Being born SGA or premature resulted in a positive predictive value of 46% for schizophrenia; negative predictive value in the absence of both features was 83%. Post hoc analyses suggested that these perinatal complications were also associated with factors indicative of increased severity of schizophrenia. Van et al. (2016) concluded that in 22q11.2 deletion syndrome, fetal growth and gestation may have a clinically significant impact on future risk of schizophrenia. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Goodman et al. (2000) reported that 8 of 15 patients with deletions in the VCF critical region 22q11.2 had elevated proline levels ranging from 278 to 849 micromol/l while 7 were in the normal range of 51 to 271 micromol/l. Goodman et al. (2000) suggested that the hyperprolinemia (239500) is caused by the hemizygous deletion of the proline oxidase gene (606810) that maps to this region. Goodman et al. (2000) concluded that elevations in plasma proline levels should be considered a biochemical feature of the chromosome 22q11.2 deletion syndromes and suggested that patients with isolated hyperprolinemia should be studied for the microdeletion at 22q11.2. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>VCFS is the most common syndrome that has palatal anomalies as a major feature. A possible strategy for early detection of VCFS is the routine screening for 22q11 deletions in all infants with cleft palate (CP). Ruiter et al. (2003) evaluated this strategy as opposed to testing on clinical suspicion alone. At the Nijmegen Cleft Palate Craniofacial Center in the Netherlands, they routinely tested 58 new patients with overt CP, using FISH, for the 22q11 deletion. One deletion was identified in a newborn girl with an overt CP who was clinically not suspected of having VCFS. Based on this study and the literature, they estimated the prevalence of 22q11 deletions among children with CP, but without any other symptoms of VCFS, to be 1 in 99. They concluded that routine FISH testing for 22q11 deletions in infants with overt CP is not indicated, provided clinical follow-up is guaranteed. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Cytogenetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The large clinical overlap between DiGeorge syndrome and velocardiofacial syndrome suggested an etiologic connection. DiGeorge syndrome is associated with microdeletions of chromosome 22q11 and is thought to be caused by reduced dosage of genes within this region, i.e., monosomy. Scambler et al. (1992) presented preliminary evidence of similar microdeletions in 22q11 in patients with VCF syndrome. Kelly et al. (1993) found monosomy for a region of 22q11 in all 12 patients with VCFS who were examined by use of DNA probes. By high-resolution banding techniques, Driscoll et al. (1992) detected an interstitial deletion of 22q11.21-q11.23 in 3 of 15 patients with VCFS. The remaining 12 patients had apparently normal chromosomes. Molecular analysis with probes from the DiGeorge chromosome region (DGCR) within 22q11 detected DNA deletions in 14 of the 15 patients. In 2 families, deletions were detected in the affected parent as well as the proband, suggesting autosomal dominant transmission of VCFS due to segregation of a deletion. Thus, further support is provided that VCFS and DGS may be the result of mutation in the same gene. </p><p>Karayiorgou et al. (1995) reported the results of 2 studies examining the genetic overlap between schizophrenia and VCFS. In the first study, they characterized 2 interstitial deletions identified on 22q11 in a sample of schizophrenic patients. The size of the deletions were estimated to be between 1.5 and 2 Mb. In the second study, they investigated whether variations in deletion size are associated with the schizophrenic phenotype in VCFS patients. The results suggested that a region of the genome that had previously been implicated by genetic linkage analysis may harbor genetic lesions that increase the susceptibility to schizophrenia. See 600850. </p><p>To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, Carlson et al. (1997) evaluated 26 VCFS patients by clinical and molecular biologic methods. The VCFS children and adolescents were found to share psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients (more than 18 years of age) were affected with bipolar spectrum disorders. Four of 6 adult patients had psychotic symptoms manifested by paranoid and grandiose delusions. Loss of heterozygosity (LOH) analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and 2 did not have a detectable deletion, even when analyzed with a large number of sequence tagged sites (STSs) at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggested a common genetic etiology. </p><p>Morrow et al. (1995) used 11 short tandem-repeat polymorphic (STRP) markers to study 15 VCFS individuals and their unaffected parents. Haplotypes generated by these markers revealed that 82% of the patients had deletions. All patients who had a deletion shared a common proximal breakpoint, while there were 2 distinct distal breakpoints. Markers D22S941 and D22S944 appeared to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. Parental origin of the deleted chromosome had no effect on the phenotypic manifestations. </p><p>By genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11, Carlson et al. (1997) found that 83% had a deletion and more than 90% of these had a similar deletion of approximately 3 Mb, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. They found no correlation between the presence or size of the deletion and the phenotype. To define further the chromosomal breakpoints among the VCFS patients, they developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that included deletion breakpoints was constructed, incorporating genes and ESTs isolated by the hybridization selection method. The ordered markers were used to examine the 2 separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, they could map the chromosome breakpoints within a single cosmid. </p><p>Edelmann et al. (1999) developed hamster-human somatic hybrid cell lines from VCFS/DGS patients and showed by use of haplotype analysis with a set of 16 ordered genetic markers on 22q11 that the breakpoints occurred within similar low copy repeats, designated LCR22s. Models were presented to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders. </p><p>Shaikh et al. (2000) completed sequencing of the 3-Mb typically deleted region (TDR) and identified 4 LCRs within it. Although the LCRs differed in content and organization of shared modules, those modules that were common between them shared 97 to 98% sequence identity with one another. Sequence analysis of rearranged junction fragments from variant deletions in 3 DGS/VCFS patients implicated the LCRs directly in the formation of 22q11.2 deletions. FISH analysis of nonhuman primates suggested that the duplication events which generated the nest of LCRs may have occurred at least 20 to 25 million years ago. </p><p>Saitta et al. (2004) traced the grandparental origin of regions flanking de novo 3-Mb deletions in 20 informative 3-generation families with DiGeorge or velocardiofacial syndromes. Haplotype reconstruction of the flanking regions showed an unexpectedly high number of proximal interchromosomal exchanges between homologs, occurring in 19 of 20 families, whereas the normal chromosome 22 in these probands showed interchromosomal exchanges in 2 of 15 informative meioses, a rate consistent with the genetic distance. Immunostaining with MLH1 (120436) antibody localized meiotic exchanges to the distal region of chromosome 22q in 75% of human spermatocytes tested, also reflecting the genetic map. There was no effect of proband gender or parental age on crossover frequency, and parental origin studies in 65 de novo 3-Mb deletions demonstrated no bias. Unlike Williams syndrome (194050), FISH analysis showed no chromosomal inversions flanked by LCRs in 22 sets of parents of 22q11-deleted patients or in 8 nondeleted patients with a DGS/VCFS phenotype. Saitta et al. (2004) concluded that significant aberrant interchromosomal exchange events during meiosis I in the proximal region of the affected chromosome 22 are the likely etiology for these deletions. Since this type of exchange occurs more often for 22q11 deletions than for deletions of 7q11, 15q11, 17p11, and 17q11, they suggested that there is a difference in the meiotic behavior of chromosome 22. </p><p>Sahoo et al. (2011) analyzed 38,779 individuals referred to the diagnostic laboratory for microarray testing for the presence of copy number variants encompassing 20 putative schizophrenia susceptibility loci. They also analyzed the indications for study for individuals with copy number variants overlapping those found in 6 individuals referred for schizophrenia. After excluding larger gains or losses that encompassed additional genes outside the candidate loci (e.g., whole-arm gains/losses), Sahoo et al. (2011) identified 1,113 individuals with copy number variants encompassing schizophrenia susceptibility loci and 37 individuals with copy number variants overlapping those present in the 6 individuals referred for schizophrenia. Of these, 1,035 had a copy number variant of 1 of 6 recurrent loci: 1q21.1 (612474, 612475), 15q11.2 (608636), 15q13.3 (612001), 16p11.2 (611913), 16p13.11 (610543, 613458), and 22q11.2 (see also 608363). The indications for study for these 1,150 individuals were diverse and included developmental delay, intellectual disability, autism spectrum, and multiple congenital anomalies. Sahoo et al. (2011) identified the 22q11.2 microdeletion in 186 individuals; 38 were de novo, 4 maternally inherited, 4 paternally inherited, and 140 of unknown inheritance. The average age at diagnosis was 7.1 years with an age range of 0.2 to 50.1 years, and the indications for study included development delay, behavioral abnormalities, dysmorphic features, multiple congenital anomalies, congenital heart defect, failure to thrive, autism, hypocalcemia, seizure disorder, postaxial polydactyly, and clubfeet. This deletion was seen in 115 of 23,250 cases referred to their laboratory for a frequency of 0.49%, and not at all in 5,674 controls for a p value of less than 0.0001 (see Itsara et al., 2009). The incidence in a schizophrenia population reported by Kirov et al. (2009) was 0.2% compared to 0.0% in their controls. Sahoo et al. (2011) concluded that the results from their study, the largest genotype-first analysis of schizophrenia susceptibility loci to that time, suggested that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and implied the existence of shared biologic pathways among multiple neurodevelopmental conditions. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Tsai et al. (1999) reported a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly, features consistent with velocardiofacial syndrome. The child did not have a 22q deletion based on FISH analysis using the probe D22S75; however, cytogenetic analysis demonstrated a terminal deletion of 4q34.2-qter. The authors suggested that a distal 4q deletion may lead to a syndrome similar to velocardiofacial syndrome and emphasized the importance of searching for other chromosome abnormalities when a phenotype of velocardiofacial syndrome is present and a 22q deletion is not detected. </p><p>Van Esch et al. (1999) reviewed 35 cases of del10p13-p14 plus one of their own (see 601362) and compared the phenotypic spectrum with that of classic DGS/VCFS associated with del22q11 as defined by Ryan et al. (1997). Both groups of patients may have facial dysmorphism, renal anomalies, hypoparathyroidism, and immune defect. However, severe growth and mental retardation were noted in almost all patients with del10p but not in those with del22q11. Heart defects were less frequent in del10p. A distinct feature in del10p was the presence of progressive sensorineural deafness, whereas in del22q11 the hearing loss was mostly conductive due to palate deformities and velopharyngeal insufficiency. In both groups, the full clinical picture was rarely seen. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Carelle-Calmels et al. (2009) noted that deletion of 22q11.2, resulting in DGS or VCFS, is usually sporadic but has been reported to be inherited in 6 to 28% of patients with these syndromes. They performed cytogenetic studies of the parents of a girl with DGS (or VCFS) who had a deletion of 22q11.2 and found an unexpected rearrangement of both 22q11.2 regions in the unaffected father. He carried a 22q11.2 deletion on one copy of chromosome 22 and a reciprocal 22q11.2 duplication (see 608363) on the other copy of chromosome 22. Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the 22q11 deletion syndrome. Carelle-Calmels et al. (2009) noted that this finding has implications for genetic counseling. </p><p>Delio et al. (2013) genotyped a total of 389 DNA samples from 22q11 deletion syndrome-affected families. A total of 219 (56%) individuals with 22q11 deletion had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, similar to data for the general population in 11 countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6 to 1.7 times greater than that for males, suggesting that for this region in the genome enhanced meiotic recombination rates, as well as other 22q11.2-specific features, could be responsible for the observed excess in maternal origin. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>See Oskarsdottir et al. (2023) and Boot et al. (2023) for clinical practice recommendations for managing children and adults with 22q11.2 deletion syndrome, respectively. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Using a YAC clone containing the VCFS critical region on chromosome 22q11 as a substrate for cDNA selection, Sirotkin et al. (1996) derived a cDNA that encodes a clathrin heavy chain gene (CLTD; 601273). FISH studies revealed that a cosmid containing the CLTD gene mapped to chromosome 22q11 and was deleted from 2 patients with VCFS who had previously been shown to have deletions of chromosome 22q11. Sirotkin et al. (1996) noted that because VCFS is a complex disorder with significant variability in phenotype and penetrance, it is likely that a number of genes in the commonly deleted region contribute to the phenotype. </p><p>Sirotkin et al. (1997) identified a novel gene, termed transmembrane protein deleted in VCFS (TMVCF; 602101), in the VCFS critical region. They localized the TMVCF gene between polymorphic markers D22S944 and D22S941, both of which are deleted in more than 80% of VCFS patients. </p><p>Carlson et al. (1997) delineated a 480-kb critical region for VCFS, including the genes for GSCL (601845), SLC25A1 (190315), CLTD, HIRA (600237), and TMVCF, as well as a number of novel ordered ESTs. </p><p>Dunham et al. (1992) pointed out that the HP500 sequence often deleted in VCFS is located within the same 450-kb yeast artificial chromosome (YAC) as the catechol-O-methyltransferase (COMT; 116790) gene, which might, therefore, be deleted also in this disorder. </p><p>Murphy et al. (1999) examined 50 adults with VCFS using a structured clinical interview to establish a DSM-IV diagnosis. Twelve percent of this sample of 50 patients were referred from a psychiatry clinic; the remainder came from genetics or cardiology. Fifteen individuals with VCFS (30%) had a psychotic disorder, with 12 (24%) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia without VCFS. Murphy et al. (1999) found no evidence that possession of the low-activity COMT allele (val158-to-met; 116790.0001) was associated with schizophrenia in their sample. </p><p>Baker et al. (2005) studied 2 hypotheses: first, that individuals with 22q11 deletion syndrome would manifest specific cognitive and neurophysiologic abnormalities in common with individuals at high risk for schizophrenia in the general population; and second, that the COMT val108/158met polymorphism would modify the severity of endophenotypic features. Adolescents and young adults with 22q11 deletion syndrome, aged 13-21, were compared with age- and IQ-matched control subjects on measures that were associated with risk for idiopathic schizophrenia. These individuals displayed poorer verbal working memory and expressive language performance than control subjects. Auditory mismatch negativity event-related potentials were reduced at frontal electrodes but intact at temporal sites. The presence of the COMT val108/158met allele on the single intact chromosome 22 was associated with more marked auditory mismatch negativity amplitude reduction and poorer neuropsychologic performance. Neither allele influenced psychiatric symptoms. </p><p>Glaser et al. (2006) tested measures of executive function, IQ, and memory in 34 children and young adults with the 22q11.2 deletion syndrome (14 hemizygous for COMT val158 and 30 for met158). No significant differences were detected between met- and val-hemizygous participants on measures of executive function. The groups did not differ on full-scale, performance, and verbal IQ or on verbal and visual memory. Glaser et al. (2006) suggested that either the COMT polymorphism has a small effect on executive function in 22q11.2 deletion syndrome or no effect exists at all. </p><p>Yagi et al. (2003) demonstrated mutations in the TBX1 gene in patients with the conotruncal anomaly face syndrome (217095)/velocardiofacial syndrome (602054.0001 and 602054.0003). </p><p>Paylor et al. (2006) identified a heterozygous 23-bp deletion in the TBX1 gene (602054.0004) in a mother and 2 sons with velocardiofacial syndrome. The mother had major depression (608516) and 1 of the sons was diagnosed with Asperger syndrome (see, e.g., 608638 and 209850). Paylor et al. (2006) suggested that the Tbx1 gene is a candidate for psychiatric disease in patients with VCFS and DiGeorge syndrome. </p><p>Kaminsky et al. (2011) presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 22q11.2 deletion was identified in 93 cases and no controls for a p value of 9.15 x 10(-21) and a frequency in cases of 1 of 169. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>McDonald-McGinn et al. (2001) reported on 30 individuals with the 22q11 deletion that were identified following the diagnosis in a relative. Sixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3- to 4-Mb deletion in most families despite wide inter- and intrafamilial variability, and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By analyzing head profile radiographs, Molsted et al. (2010) found an increased frequency of abnormalities in the morphology of the sella turcica in 33 patients with VCFS, including 30 with either velopharyngeal insufficiency or palatal abnormalities, compared to controls. VCFS patients showed deviations mostly in the posterior part of the dorsum sellae, and patients had increased cranial base angles compared to controls. Molsted et al. (2010) noted that abnormal morphology of the cranial base and the sella turcica should be considered a cranial malformation. Taking into account that the main features of the disorder are palatal abnormalities, thymic hypoplasia, hypothyroidism, and cardiac defects, the findings of Molsted et al. (2010) suggested a defect in the neural crest developmental field that includes the thyroid, thymus, and conotruncal septum of the heart. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Jerome and Papaioannou (2001) investigated the potential role of the Tbx1 gene (602054) in the causation of the DiGeorge/velocardiofacial syndrome (DGS/VCFS) phenotype. This gene, which encodes a transcription factor of the T-box family, maps to 22q11. They produced a null mutation of the Tbx1 gene in mice and found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1 -/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae, and cleft palate. On the basis of this phenotype in mice, Jerome and Papaioannou (2001) proposed that TBX1 in humans has a role in the etiology of DGS/VCFS. </p><p>Merscher et al. (2001) used a Cre-loxP strategy to generate mice that were hemizygous for a 1.5-Mb deletion corresponding to that on 22q11 in VCFS/DGS patients. These mice exhibited significant perinatal lethality and had conotruncal and parathyroid defects. The conotruncal defects could be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 developed conotruncal defects. These results together with the expression patterns of TBX1 suggested a major role for the TBX1 gene in the molecular etiology of VCFS/DGS. </p><p>Funke et al. (2001) reported that mice overexpressing 4 transgenes (PNUTL1, 602724; GP1BB, 138720; TBX1; and WDR14, 610778) had chronic otitis media, a hyperactive circling behavior, and sensorineural hearing loss. This was associated with middle and inner ear malformations analogous to human Mondini dysplasia, reported to occur in VCFS/DGS patients. Based upon its pattern of expression in the ear and functional studies of the gene, the authors hypothesized that Tbx1 likely plays a central role in the etiology of ear defects in these mice, and that haploinsufficiency of TBX1 may be responsible for ear disorders in VCFS/DGS patients. </p><p>The CRKL gene (602007) encodes an SH2-SH3-SH3 adaptor protein closely related to the Crk (164762) gene products. CRKL maps within the common deletion region for DGS/VCFS. Guris et al. (2001) reported that mice homozygous for a targeted null mutation at the Crkl locus exhibited defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands, and craniofacial structures. They showed that the migration and early expansion of the neural crest cells is unaffected in Crkl -/- embryos. Guris et al. (2001) concluded that the similarity between the Crkl -/- phenotype and the clinical manifestations of DGS/VCFS implicate defects in CRKL-mediated signaling pathways as part of the molecular mechanism underlying this syndrome. </p><p>Schinke and Izumo (2001) reviewed the genetic structure of the 22q11 region associated with DGS and the syntenic region of mouse chromosome 16. The gene order is inverted between human and mouse in a segment of this region. A table accompanying the figure summarized the phenotypes of mice homozygous or heterozygous mutant for chromosomal deletions or gene mutations of specific regions. </p><p>Df1/+ mice, which model del22q11, present with reduced penetrance of cardiovascular defects similar to those seen in deleted patients but not with other del22q11-like findings. The reduced penetrance of cardiovascular defects is caused by the ability of mutant embryos to recover from a fourth pharyngeal arch artery growth abnormality that is fully penetrant in early embryos. Taddei et al. (2001) showed that genetic background has a major effect on the penetrance of cardiovascular defects by affecting this embryonic recovery process. This effect could not be explained by allelic variation at the haploid locus, and is likely to be caused by genetic modifiers elsewhere in the genome. Taddei et al. (2001) also showed that genetic factors control extension of the Df1/+ phenotype to include thymic and parathyroid anomalies, establishing the Df1 mouse as a model for the genetic analysis of 3 major features of human del22q11 syndrome. They found that in Df1/+ mice, as in human patients, expression of the heart and thymic phenotypes are essentially independent of each other, suggesting that they may be controlled by different genetic modifiers. </p><p>Stalmans et al. (2003) reported that absence of the 164-amino acid isoform of Vegf (Vegf164; see 192240), the only one that binds neuropilin-1 (602069), causes birth defects in mice reminiscent of those found in patients with deletion of 22q11. The close correlation of birth and vascular defects indicated that vascular dysgenesis may pathogenetically contribute to the birth defects. Vegf interacted with Tbx1 (602054), as Tbx1 expression was reduced in Vegf164-deficient embryos and knocked-down Vegf levels enhanced the pharyngeal arch artery defects induced by Tbx1 knockdown in zebrafish. Moreover, initial evidence suggested that a Vegf promoter haplotype was associated with an increased risk for cardiovascular birth defects in del22q11 individuals. Stalmans et al. (2003) concluded that genetic data in mouse, fish, and human indicated that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome. </p><p>Liao et al. (2004) reported that mice hemizygous for a null allele of Tbx1 had mild malformations, while homozygotes had severe malformations in the affected structures. Neither pattern of malformation precisely modeled VCFS or DGS. Furthermore, bacterial artificial chromosome (BAC) transgenic mice overexpressing human TBX1 and 3 other transgenes had similar malformations to VCFS/DGS patients. By employing genetic complementation studies, the authors demonstrated that altered TBX1 dosage, rather than overexpression of the other transgenes, was responsible for most of the defects in the BAC transgenic mice. Furthermore, the full spectrum of VCFS/DGS malformations was elicited in a TBX1 dose-dependent manner, thus providing a molecular basis for the pathogenesis and varied expressivity of the syndrome. </p><p>Sigurdsson et al. (2010) studied Df(16)A(+/-) mice, which model a microdeletion on human chromosome 22q11.2 that constitutes one of the largest known genetic risk factors for schizophrenia. To examine functional connectivity in these mice, Sigurdsson et al. (2010) measured the synchronization of neural activity between the hippocampus and the prefrontal cortex during the performance of a task requiring working memory, which is one of the cognitive functions disrupted in the disease. In wildtype mice, hippocampal-prefrontal synchrony increased during working memory performance, consistent with previous reports in rats. Df(16)A(+/-) mice, which are impaired in the acquisition of the task, showed drastically reduced synchrony, measured both by phase-locking of prefrontal cells to hippocampal theta oscillations and by coherence of prefrontal and hippocampal local field potentials. Furthermore, the magnitude of hippocampal-prefrontal coherence at the onset of training could be used to predict the time it took the Df(16)A(+/-) mice to learn the task and increased more slowly during task acquisition. Sigurdsson et al. (2010) concluded that their data suggested how the deficits in functional connectivity observed in patients with schizophrenia may be realized at the single-neuron level, and further suggested that impaired long-range synchrony of neural activity is one consequence of the 22q11.2 deletion and may be a fundamental component of the pathophysiology underlying schizophrenia. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Williams et al. (1985)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Baker, K., Baldeweg, T., Sivagnanasundaram, S., Scambler, P., Skuse, D.
<strong>COMT val108/158met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome.</strong>
Biol. Psychiat. 58: 23-31, 2005.
[PubMed: 15935994]
[Full Text: https://doi.org/10.1016/j.biopsych.2005.03.020]
</p>
</li>
<li>
<p class="mim-text-font">
Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., Gatzoulis, M. A.
<strong>Clinical features of 78 adults with 22q11 deletion syndrome.</strong>
Am. J. Med. Genet. 138A: 307-313, 2005.
[PubMed: 16208694]
[Full Text: https://doi.org/10.1002/ajmg.a.30984]
</p>
</li>
<li>
<p class="mim-text-font">
Beemer, F. A., de Nef, J. J. E. M., Delleman, J. W., Bleeker-Wagemakers, E. M., Shprintzen, R. J.
<strong>Additional eye findings in a girl with the velo-cardio-facial syndrome. (Letter)</strong>
Am. J. Med. Genet. 24: 541-542, 1986.
[PubMed: 3089013]
[Full Text: https://doi.org/10.1002/ajmg.1320240319]
</p>
</li>
<li>
<p class="mim-text-font">
Boot, E., Oskarsdottir, S., Loo, J. C. Y., Crowley, T. B., Orchanian-Cheff, A., Andrade, D. M., Arganbright, J. M., Castelein, R. M., Cserti-Gazdewich, C., de Reuver, S., Fiksinski, A. M., Klingberg, G., and 17 others.
<strong>Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome.</strong>
Genet. Med. 25: 100344, 2023.
[PubMed: 36729052]
[Full Text: https://doi.org/10.1016/j.gim.2022.11.012]
</p>
</li>
<li>
<p class="mim-text-font">
Butcher, N. J., Chow, E. W. C., Costain, G., Karas, D., Ho, A., Bassett, A. S.
<strong>Functional outcomes of adults with 22q11.2 deletion syndrome.</strong>
Genet. Med. 14: 836-843, 2012.
[PubMed: 22744446]
[Full Text: https://doi.org/10.1038/gim.2012.66]
</p>
</li>
<li>
<p class="mim-text-font">
Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., Kuhn, P., Arrive, M., Gilch, C., Schmitt, E., Fehrenbach, S., Schnebelen, A., Frebourg, T., Flori, E.
<strong>Genetic compensation in a human genomic disorder.</strong>
New Eng. J. Med. 360: 1211-1216, 2009.
[PubMed: 19297573]
[Full Text: https://doi.org/10.1056/NEJMoa0806544]
</p>
</li>
<li>
<p class="mim-text-font">
Carlson, C., Papolos, D., Pandita, R. K., Faedda, G. L., Veit, S., Goldberg, R., Shprintzen, R., Kucherlapati, R., Morrow, B.
<strong>Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.</strong>
Am. J. Hum. Genet. 60: 851-859, 1997.
[PubMed: 9106531]
</p>
</li>
<li>
<p class="mim-text-font">
Carlson, C., Sirotkin, H., Pandita, R., Goldberg, R., McKie, J., Wadey, R., Patanjali, S. R., Weissman, S. M., Anyane-Yeboa, K., Warburton, D., Scambler, P., Shprintzen, R., Kucherlapati, R., Morrow, B. E.
<strong>Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.</strong>
Am. J. Hum. Genet. 61: 620-629, 1997.
[PubMed: 9326327]
[Full Text: https://doi.org/10.1086/515508]
</p>
</li>
<li>
<p class="mim-text-font">
Conway, K., Gibson, R. L., Perkins, J., Cunningham, M. L.
<strong>Pulmonary agenesis: expansion of the VCFS phenotype.</strong>
Am. J. Med. Genet. 113: 89-92, 2002.
[PubMed: 12400071]
[Full Text: https://doi.org/10.1002/ajmg.10673]
</p>
</li>
<li>
<p class="mim-text-font">
Cunningham, M. L., Perry, R. J., Eby, P. R., Gibson, R. L., Opheim, K. E., Manning, S. C.
<strong>Primary pulmonary dysgenesis in velocardiofacial syndrome: a second patient. (Letter)</strong>
Am. J. Med. Genet. 121A: 177-179, 2003.
[PubMed: 12910501]
[Full Text: https://doi.org/10.1002/ajmg.a.20142]
</p>
</li>
<li>
<p class="mim-text-font">
Delio, M., Guo, T., McDonald-McGinn, D. M., Zackai, E., Herman, S., Kaminetzky, M., Higgins, A. M., Coleman, K., Chow, C., Jalbrzikowski, M., Bearden, C. E., Bailey, A., and 45 others.
<strong>Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes.</strong>
Am. J. Hum. Genet. 92: 439-447, 2013. Note: Erratum: Am. J. Hum. Genet. 92: 637 only, 2013.
[PubMed: 23453669]
[Full Text: https://doi.org/10.1016/j.ajhg.2013.01.018]
</p>
</li>
<li>
<p class="mim-text-font">
Devriendt, K., Moerman, P., Van Schoubroeck, D., Vandenberghe, K., Fryns, J.-P.
<strong>Chromosome 22q11 deletion presenting as the Potter sequence.</strong>
J. Med. Genet. 34: 423-425, 1997.
[PubMed: 9152843]
[Full Text: https://doi.org/10.1136/jmg.34.5.423]
</p>
</li>
<li>
<p class="mim-text-font">
Digilio, M. C., Marino, B., Cappa, M., Cambiaso, P., Giannotti, A., Dallapiccola, B.
<strong>Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome (deletion 22q11.2 syndrome).</strong>
Genet. Med. 3: 30-33, 2001.
[PubMed: 11339374]
[Full Text: https://doi.org/10.1097/00125817-200101000-00007]
</p>
</li>
<li>
<p class="mim-text-font">
Driscoll, D. A., Spinner, N. B., Budarf, M. L., McDonald-McGinn, D. M., Zackai, E. H., Goldberg, R. B., Shprintzen, R. J., Saal, H. M., Zonana, J., Jones, M. C., Mascarello, J. T., Emanuel, B. S.
<strong>Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome.</strong>
Am. J. Med. Genet. 44: 261-268, 1992.
[PubMed: 1360769]
[Full Text: https://doi.org/10.1002/ajmg.1320440237]
</p>
</li>
<li>
<p class="mim-text-font">
Dunham, I., Collins, J., Wadey, R., Scambler, P.
<strong>Possible role for COMT in psychosis associated with velo-cardio-facial syndrome. (Letter)</strong>
Lancet 340: 1361-1362, 1992.
[PubMed: 1360084]
[Full Text: https://doi.org/10.1016/0140-6736(92)92553-r]
</p>
</li>
<li>
<p class="mim-text-font">
Edelmann, L., Pandita, R. K., Spiteri, E., Funke, B., Goldberg, R., Palanisamy, N., Chaganti, R. S. K., Magenis, E., Shprintzen, R. J., Morrow, B. E.
<strong>A common molecular basis for rearrangement disorders on chromosome 22q11.</strong>
Hum. Molec. Genet. 8: 1157-1167, 1999.
[PubMed: 10369860]
[Full Text: https://doi.org/10.1093/hmg/8.7.1157]
</p>
</li>
<li>
<p class="mim-text-font">
Evers, L. J. M., De Die-Smulders, C. E. M., Smeets, E. E. J., Clerkx, M. G. M., Curfs, L. M. G.
<strong>The velo-cardio-facial syndrome: the spectrum of psychiatric problems and cognitive deterioration at adult age.</strong>
Genet. Counsel. 20: 307-315, 2009.
[PubMed: 20162865]
</p>
</li>
<li>
<p class="mim-text-font">
Evers, L. J. M., Vermaak, M. P., Engelen, J. J. M., Curfs, L. M. G.
<strong>The velocardiofacial syndrome in older age: dementia and autistic features.</strong>
Genet. Counsel. 17: 333-340, 2006.
[PubMed: 17100202]
</p>
</li>
<li>
<p class="mim-text-font">
Fitch, N.
<strong>Velo-cardio-facial syndrome and eye abnormality. (Letter)</strong>
Am. J. Med. Genet. 15: 669 only, 1983.
</p>
</li>
<li>
<p class="mim-text-font">
Forrester, S., Kovach, M. J., Smith, R. E., Rimer, L., Wesson, M.
<strong>Kousseff syndrome caused by deletion of chromosome 22q11-13.</strong>
Am. J. Med. Genet. 112: 338-342, 2002.
[PubMed: 12376934]
[Full Text: https://doi.org/10.1002/ajmg.10625]
</p>
</li>
<li>
<p class="mim-text-font">
Funke, B., Epstein, J. A., Kochilas, L. K., Lu, M. M., Pandita, R. K., Liao, J., Bauerndistel, R., Schuler, T., Schorle, H., Brown, M. C., Adams, J., Morrow, B. E.
<strong>Mice overexpressing genes from the 22q11 region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have middle and inner ear defects.</strong>
Hum. Molec. Genet. 10: 2549-2556, 2001.
[PubMed: 11709542]
[Full Text: https://doi.org/10.1093/hmg/10.22.2549]
</p>
</li>
<li>
<p class="mim-text-font">
Glaser, B., Debbane, M., Hinard, C., Morris, M. A., Dahoun, S. P., Antonarakis, S. E., Eliez, S.
<strong>No evidence for an effect of COMT val158-to-met genotype on executive function in patients with 22q11 deletion syndrome.</strong>
Am. J. Psychiat. 163: 537-539, 2006.
[PubMed: 16513880]
[Full Text: https://doi.org/10.1176/appi.ajp.163.3.537]
</p>
</li>
<li>
<p class="mim-text-font">
Goldberg, R., Motzkin, B., Marion, R., Scambler, P. J., Shprintzen, R. J.
<strong>Velo-cardio-facial syndrome: a review of 120 patients.</strong>
Am. J. Med. Genet. 45: 313-319, 1993.
[PubMed: 8434617]
[Full Text: https://doi.org/10.1002/ajmg.1320450307]
</p>
</li>
<li>
<p class="mim-text-font">
Golding-Kushner, K. J., Weller, G., Shprintzen, R. J.
<strong>Velo-cardio-facial syndrome: language and psychological profiles.</strong>
J. Craniofac. Genet. Dev. Biol. 5: 259-266, 1985.
[PubMed: 4044789]
</p>
</li>
<li>
<p class="mim-text-font">
Goodman, B. K., Rutberg, J., Lin, W. W., Pulver, A. E., Thomas, G. H., Geraghty, M. T.
<strong>Hyperprolinaemia in patients with deletion (22)(q11.2) syndrome.</strong>
J. Inherit. Metab. Dis. 23: 847-848, 2000.
[PubMed: 11196113]
[Full Text: https://doi.org/10.1023/a:1026773005303]
</p>
</li>
<li>
<p class="mim-text-font">
Gothelf, D., Presburger, G., Levy, D., Nahmani, A., Burg, M., Berant, M., Blieden, L. C., Finkelstein, Y., Frisch, A., Apter, A., Weizman, A.
<strong>Genetic, developmental, and physical factors associated with attention deficit hyperactivity disorder in patients with velocardiofacial syndrome.</strong>
Am. J. Med. Genet. 126B: 116-121, 2004.
[PubMed: 15048660]
[Full Text: https://doi.org/10.1002/ajmg.b.20144]
</p>
</li>
<li>
<p class="mim-text-font">
Gothelf, D., Presburger, G., Zohar, A. H., Burg, M., Nahmani, A., Frydman, M., Shohat, M., Inbar, D., Aviram-Goldring, A., Yeshaya, J., Steinberg, T., Finkelstein, Y., Frisch, A., Weizman, A., Apter, A.
<strong>Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome.</strong>
Am. J. Med. Genet. 126B: 99-105, 2004.
[PubMed: 15048657]
[Full Text: https://doi.org/10.1002/ajmg.b.20124]
</p>
</li>
<li>
<p class="mim-text-font">
Guris, D. L., Fantes, J., Tara, D., Druker, B. J., Imamoto, A.
<strong>Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome.</strong>
Nature Genet. 27: 293-298, 2001.
[PubMed: 11242111]
[Full Text: https://doi.org/10.1038/85855]
</p>
</li>
<li>
<p class="mim-text-font">
Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., Mefford, H., Ying, P., Nickerson, D. A., Eichler, E. E.
<strong>Population analysis of large copy number variants and hotspots of human genetic disease.</strong>
Am. J. Hum. Genet. 84: 148-161, 2009.
[PubMed: 19166990]
[Full Text: https://doi.org/10.1016/j.ajhg.2008.12.014]
</p>
</li>
<li>
<p class="mim-text-font">
Jawad, A. F., McDonald-McGinn, D. M., Zackai, E., Sullivan, K. E.
<strong>Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).</strong>
J. Pediat. 139: 715-723, 2001.
[PubMed: 11713452]
[Full Text: https://doi.org/10.1067/mpd.2001.118534]
</p>
</li>
<li>
<p class="mim-text-font">
Jerome, L. A., Papaioannou, V. E.
<strong>DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.</strong>
Nature Genet. 27: 286-291, 2001.
[PubMed: 11242110]
[Full Text: https://doi.org/10.1038/85845]
</p>
</li>
<li>
<p class="mim-text-font">
Kaminsky, E. B., Kaul, V., Paschall, J., Church, D. M., Bunke, B., Kunig, D., Moreno-De-Luca, D., Moreno-De-Luca, A., Mulle, J. G., Warren, S. T., Richard, G., Compton, J. G., and 22 others.
<strong>An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.</strong>
Genet. Med. 13: 777-784, 2011.
[PubMed: 21844811]
[Full Text: https://doi.org/10.1097/GIM.0b013e31822c79f9]
</p>
</li>
<li>
<p class="mim-text-font">
Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., Lasseter, V. K., Eisen, H., Childs, B., Kazazian, H. H., Kucherlapati, R., Antonarakis, S. E., Pulver, A. E., Housman, D. E.
<strong>Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.</strong>
Proc. Nat. Acad. Sci. 92: 7612-7616, 1995.
[PubMed: 7644464]
[Full Text: https://doi.org/10.1073/pnas.92.17.7612]
</p>
</li>
<li>
<p class="mim-text-font">
Kawame, H., Adachi, M., Tachibana, K., Kurosawa, K., Ito, F., Gleason, M. M., Weinzimer, S., Levitt-Katz, L., Sullivan, K., McDonald-McGinn, D. M.
<strong>Graves&#x27; disease in patients with 22q11.2 deletion.</strong>
J. Pediat. 139: 892-895, 2001.
[PubMed: 11743521]
[Full Text: https://doi.org/10.1067/mpd.2001.119448]
</p>
</li>
<li>
<p class="mim-text-font">
Kelly, D., Goldberg, R., Wilson, D., Lindsay, E., Carey, A., Goodship, J., Burn, J., Cross, I., Shprintzen, R. J., Scambler, P. J.
<strong>Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.</strong>
Am. J. Med. Genet. 45: 308-312, 1993.
[PubMed: 8434616]
[Full Text: https://doi.org/10.1002/ajmg.1320450306]
</p>
</li>
<li>
<p class="mim-text-font">
Kessler-Icekson, G., Birk, E., Weintraub, A. Y., Barhum, Y., Kotlyar, V., Schlesinger, H., Rockah, R., Vidne, B. A., Frisch, A.
<strong>Association of tetralogy of Fallot with a distinct region of del22q11.2.</strong>
Am. J. Med. Genet. 107: 294-298, 2002.
[PubMed: 11840485]
[Full Text: https://doi.org/10.1002/ajmg.10166]
</p>
</li>
<li>
<p class="mim-text-font">
Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Owen, M. J., O'Donovan, M. C.
<strong>Support for the involvement of large copy number variants in the pathogenesis of schizophrenia.</strong>
Hum. Molec. Genet. 18: 1497-1503, 2009.
[PubMed: 19181681]
[Full Text: https://doi.org/10.1093/hmg/ddp043]
</p>
</li>
<li>
<p class="mim-text-font">
Kok, L. L., Solman, R. T.
<strong>Velocardiofacial syndrome: learning difficulties and intervention.</strong>
J. Med. Genet. 32: 612-618, 1995.
[PubMed: 7473652]
[Full Text: https://doi.org/10.1136/jmg.32.8.612]
</p>
</li>
<li>
<p class="mim-text-font">
Kousseff, B. G.
<strong>Sacral meningocele with conotruncal heart defects: a possible autosomal recessive trait.</strong>
Pediatrics 74: 395-398, 1984.
[PubMed: 6472972]
</p>
</li>
<li>
<p class="mim-text-font">
Liao, J., Kochilas, L., Nowotschin, S., Arnold, J. S., Aggarwal, V. S., Epstein, J. A., Brown, M. C., Adams, J., Morrow, B. E.
<strong>Full spectrum of malformations in velo-cardio-facial syndrome/DiGeorge syndrome mouse models by altering Tbx1 dosage.</strong>
Hum. Molec. Genet. 13: 1577-1585, 2004.
[PubMed: 15190012]
[Full Text: https://doi.org/10.1093/hmg/ddh176]
</p>
</li>
<li>
<p class="mim-text-font">
Lipson, A. H., Yuille, D., Angel, M., Thompson, P. G., Vandervoord, J. G., Beckenham, E. J.
<strong>Velocardiofacial (Shprintzen) syndrome: an important syndrome for the dysmorphologist to recognize.</strong>
J. Med. Genet. 28: 596-604, 1991.
[PubMed: 1956057]
[Full Text: https://doi.org/10.1136/jmg.28.9.596]
</p>
</li>
<li>
<p class="mim-text-font">
Lynch, D. R., McDonald-McGinn, D. M., Zackai, E. H., Emanuel, B. S., Driscoll, D. A., Whitaker, L. A., Fischbeck, K. H.
<strong>Cerebellar atrophy in a patient with velocardiofacial syndrome.</strong>
J. Med. Genet. 32: 561-563, 1995.
[PubMed: 7562973]
[Full Text: https://doi.org/10.1136/jmg.32.7.561]
</p>
</li>
<li>
<p class="mim-text-font">
Maclean, K., Field, M. J., Colley, A. S., Mowat, D. R., Sparrow, D. B., Dunwoodie, S. L., Kirk, E. P. E.
<strong>Kousseff syndrome: a causally heterogeneous disorder.</strong>
Am. J. Med. Genet. 124A: 307-312, 2004.
[PubMed: 14708106]
[Full Text: https://doi.org/10.1002/ajmg.a.20418]
</p>
</li>
<li>
<p class="mim-text-font">
Makita, Y., Masuno, M., Imaizumi, K., Tachibana, K., Kuroki, Y.
<strong>Idiopathic hypoparathyroidism in two patients with 22q11 microdeletion. (Letter)</strong>
J. Med. Genet. 32: 669, 1995.
[PubMed: 7473668]
[Full Text: https://doi.org/10.1136/jmg.32.8.669]
</p>
</li>
<li>
<p class="mim-text-font">
Martin, B., Fananas, L., Gutierrez, B., Chow, E. W. C., Bassett, A. S.
<strong>Dermatoglyphic profile in 22q deletion syndrome.</strong>
Am. J. Med. Genet. 128B: 46-49, 2004.
[PubMed: 15211630]
[Full Text: https://doi.org/10.1002/ajmg.b.30034]
</p>
</li>
<li>
<p class="mim-text-font">
McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A., Finucane, B., Driscoll, D. A., Emanuel, B. S., Zackai, E. H.
<strong>Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!</strong>
Genet. Med. 3: 23-29, 2001.
[PubMed: 11339373]
[Full Text: https://doi.org/10.1097/00125817-200101000-00006]
</p>
</li>
<li>
<p class="mim-text-font">
McElhinney, D. B., McDonald-McGinn, D., Zackai, E. H., Goldmuntz, E.
<strong>Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age.</strong>
Pediatrics 108: e104, 2001. Note: Electronic Article.
[PubMed: 11731631]
[Full Text: https://doi.org/10.1542/peds.108.6.e104]
</p>
</li>
<li>
<p class="mim-text-font">
Meinecke, P., Beemer, F. A., Schinzel, A., Kushnick, T.
<strong>The velo-cardio-facial (Shprintzen) syndrome: clinical variability in eight patients.</strong>
Europ. J. Pediat. 145: 539-544, 1986.
[PubMed: 3816857]
[Full Text: https://doi.org/10.1007/BF02429059]
</p>
</li>
<li>
<p class="mim-text-font">
Merscher, S., Funke, B., Epstein, J. A., Heyer, J., Puech, A., Lu, M. M., Xavier, R. J., Demay, M. B., Russell, R. G., Factor, S., Tokooya, K., St. Jore, B., and 12 others.
<strong>TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.</strong>
Cell 104: 619-629, 2001.
[PubMed: 11239417]
[Full Text: https://doi.org/10.1016/s0092-8674(01)00247-1]
</p>
</li>
<li>
<p class="mim-text-font">
Molsted, K., Boers, M., Kjar, I.
<strong>The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field.</strong>
Am. J. Med. Genet. 152A: 1450-1457, 2010.
[PubMed: 20503320]
[Full Text: https://doi.org/10.1002/ajmg.a.33381]
</p>
</li>
<li>
<p class="mim-text-font">
Morrow, B., Goldberg, R., Carlson, C., Das Gupta, R., Sirotkin, H., Collins, J., Dunham, I., O'Donnell, H., Scambler, P., Shprintzen, R., Kucherlapati, R.
<strong>Molecular definition of the 22q11 deletions in velo-cardio-facial syndrome.</strong>
Am. J. Hum. Genet. 56: 1391-1403, 1995.
[PubMed: 7762562]
</p>
</li>
<li>
<p class="mim-text-font">
Murphy, K. C., Jones, L. A., Owen, M. J.
<strong>High rates of schizophrenia in adults with velo-cardio-facial syndrome.</strong>
Arch. Gen. Psychiat. 56: 940-945, 1999.
[PubMed: 10530637]
[Full Text: https://doi.org/10.1001/archpsyc.56.10.940]
</p>
</li>
<li>
<p class="mim-text-font">
Nickel, R. E., Pillers, D.-A. M., Merkens, M., Magenis, R. E., Driscoll, D. A., Emanuel, B. S., Zonana, J.
<strong>Velo-cardial-facial syndrome and DiGeorge sequence with meningomyelocele and deletions of the 22q11 region.</strong>
Am. J. Med. Genet. 52: 445-449, 1994.
[PubMed: 7747757]
[Full Text: https://doi.org/10.1002/ajmg.1320520410]
</p>
</li>
<li>
<p class="mim-text-font">
Oskarsdottir, S., Boot, E., Crowley, T. B., Loo, J. C. Y., Arganbright, J. M., Armando, M., Baylis, A. L., Breetvelt, E. J., Castelein, R. M., Chadehumbe, M., Cielo, C. M., de Reuver, S., and 28 others.
<strong>Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome.</strong>
Genet. Med. 25: 100338, 2023.
[PubMed: 36729053]
[Full Text: https://doi.org/10.1016/j.gim.2022.11.006]
</p>
</li>
<li>
<p class="mim-text-font">
Paylor, R., Glaser, B., Mupo, A., Ataliotis, P., Spencer, C., Sobotka, A., Sparks, C., Choi, C.-H., Oghalai, J., Curran, S., Murphy, K. C., Monks, S., Williams, N., O'Donovan, M. C., Owen, M. J., Scambler, P. J., Lindsay, E.
<strong>Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.</strong>
Proc. Nat. Acad. Sci. 103: 7729-7734, 2006.
[PubMed: 16684884]
[Full Text: https://doi.org/10.1073/pnas.0600206103]
</p>
</li>
<li>
<p class="mim-text-font">
Pulver, A. E., Nestadt, G., Goldberg, R., Shprintzen, R. J., Lamacz, M., Wolyniec, P. S., Morrow, B., Karayiogou, M., Antonarakis, S. E., Housman, D., Kucherlapati, R.
<strong>Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.</strong>
J. Nerv. Ment. Dis. 182: 476-478, 1994.
[PubMed: 8040660]
[Full Text: https://doi.org/10.1097/00005053-199408000-00010]
</p>
</li>
<li>
<p class="mim-text-font">
Ruiter, E. M., Bongers, E. M. H. F., Smeets, D. F. C. M., Kuijpers-Jagtman, A. M., Hamel, B. C. J.
<strong>No justification of routine screening for 22q11 deletions in patients with overt cleft palate.</strong>
Clin. Genet. 64: 216-219, 2003.
[PubMed: 12919136]
[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00134.x]
</p>
</li>
<li>
<p class="mim-text-font">
Ryan, A. K., Goodship, J. A., Wilson, D. I., Philip, N., Levy, A., Seidel, H., Schuffenhauer, S., Oechsler, H., Belohradsky, B., Prieur, M., Aurias, A., Raymond, F. L., and 17 others.
<strong>Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study.</strong>
J. Med. Genet. 34: 798-804, 1997.
[PubMed: 9350810]
[Full Text: https://doi.org/10.1136/jmg.34.10.798]
</p>
</li>
<li>
<p class="mim-text-font">
Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., Shaffer, L. G.
<strong>Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems.</strong>
Genet. Med. 13: 868-880, 2011.
[PubMed: 21792059]
[Full Text: https://doi.org/10.1097/GIM.0b013e3182217a06]
</p>
</li>
<li>
<p class="mim-text-font">
Saitta, S. C., Harris, S. E., Gaeth, A. P., Driscoll, D. A., McDonald-McGinn, D. M., Maisenbacher, M. K., Yersak, J. M., Chakraborty, P. K., Hacker, A. M., Zackai, E. H., Ashley, T., Emanuel, B. S.
<strong>Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion.</strong>
Hum. Molec. Genet. 13: 417-428, 2004.
[PubMed: 14681306]
[Full Text: https://doi.org/10.1093/hmg/ddh041]
</p>
</li>
<li>
<p class="mim-text-font">
Sandrin-Garcia, P., Macedo, C., Martelli, L. R., Ramos, E. S., Guion-Almeida, M. L., Richieri-Costa, A., Passos, G. A. S.
<strong>Recurrent 22q11.2 deletion in a sibship suggestive of parental germline mosaicism in velocardiofacial syndrome.</strong>
Clin. Genet. 61: 380-383, 2002.
[PubMed: 12081724]
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.610511.x]
</p>
</li>
<li>
<p class="mim-text-font">
Scambler, P. J., Kelly, D., Lindsay, E., Williamson, R., Goldberg, R., Shprintzen, R., Wilson, D. I., Goodship, J. A., Cross, I. E., Burn, J.
<strong>Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus.</strong>
Lancet 339: 1138-1139, 1992.
[PubMed: 1349369]
[Full Text: https://doi.org/10.1016/0140-6736(92)90734-k]
</p>
</li>
<li>
<p class="mim-text-font">
Schinke, M., Izumo, S.
<strong>Deconstructing DiGeorge syndrome.</strong>
Nature Genet. 27: 238-240, 2001.
[PubMed: 11242098]
[Full Text: https://doi.org/10.1038/85784]
</p>
</li>
<li>
<p class="mim-text-font">
Scire, G., Dallapiccola, B., Iannetti, P., Bonaiuto, F., Galasso, C., Mingarelli, R., Boscherini, B.
<strong>Hypoparathyroidism as the major manifestation in two patients with 22q11 deletions.</strong>
Am. J. Med. Genet. 52: 478-482, 1994.
[PubMed: 7747762]
[Full Text: https://doi.org/10.1002/ajmg.1320520415]
</p>
</li>
<li>
<p class="mim-text-font">
Shaikh, T. H., Kurahashi, H., Saitta, S. C., O'Hare, A. M., Hu, P., Roe, B. A., Driscoll, D. A., McDonald-McGinn, D. M., Zackai, E. H., Budarf, M. L., Emanuel, B. S.
<strong>Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.</strong>
Hum. Molec. Genet. 9: 489-501, 2000.
[PubMed: 10699172]
[Full Text: https://doi.org/10.1093/hmg/9.4.489]
</p>
</li>
<li>
<p class="mim-text-font">
Shprintzen, R. J., Goldberg, R. B., Young, D., Wolford, L.
<strong>The velo-cardio-facial syndrome: a clinical and genetic analysis.</strong>
Pediatrics 67: 167-172, 1981.
[PubMed: 7243439]
</p>
</li>
<li>
<p class="mim-text-font">
Shprintzen, R. J., Goldberg, R., Golding-Kushner, K. J., Marion, R.
<strong>Late-onset psychosis in the velo-cardio-facial syndrome.</strong>
Am. J. Med. Genet. 42: 141-142, 1992.
[PubMed: 1308357]
[Full Text: https://doi.org/10.1002/ajmg.1320420131]
</p>
</li>
<li>
<p class="mim-text-font">
Shprintzen, R. J., Wang, F., Goldberg, R., Marion, R.
<strong>The expanded velo-cardio-facial syndrome (VCF): additional features of the most common clefting syndrome. (Abstract)</strong>
Am. J. Hum. Genet. 37: A77, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Sigurdsson, T., Stark, K. L., Karayiorgou, M., Gogos, J. A., Gordon, J. A.
<strong>Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.</strong>
Nature 464: 763-767, 2010.
[PubMed: 20360742]
[Full Text: https://doi.org/10.1038/nature08855]
</p>
</li>
<li>
<p class="mim-text-font">
Sirotkin, H., Morrow, B., DasGupta, R., Goldberg, R., Patanjali, S. R., Shi, G., Cannizzaro, L., Shprintzen, R., Weissman, S. M., Kucherlapati, R.
<strong>Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.</strong>
Hum. Molec. Genet. 5: 617-624, 1996.
[PubMed: 8733128]
[Full Text: https://doi.org/10.1093/hmg/5.5.617]
</p>
</li>
<li>
<p class="mim-text-font">
Sirotkin, H., Morrow, B., Saint-Jore, B., Puech, A., Das Gupta, R., Patanjali, S. R., Skoultchi, A., Weissman, S. M., Kucherlapati, R.
<strong>Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome.</strong>
Genomics 42: 245-251, 1997.
[PubMed: 9192844]
[Full Text: https://doi.org/10.1006/geno.1997.4734]
</p>
</li>
<li>
<p class="mim-text-font">
Stalmans, I., Lambrechts, D., De Smet, F., Jansen, S., Wang, J., Maity, S., Kneer, P., von der Ohe, M., Swillen, A., Maes, C., Gewillig, M., Molin, D. G. M., and 20 others.
<strong>VEGF: a modifier of the del22q11 (DiGeorge) syndrome?</strong>
Nature Med. 9: 173-182, 2003.
[PubMed: 12539040]
[Full Text: https://doi.org/10.1038/nm819]
</p>
</li>
<li>
<p class="mim-text-font">
Sundaram, U. T., McDonald-McGinn, D. M., Huff, D., Emanuel, B. S., Zackai, E. H., Driscoll, D. A., Bodurtha, J.
<strong>Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome.</strong>
Am. J. Med. Genet. 143A: 2016-2018, 2007.
[PubMed: 17676598]
[Full Text: https://doi.org/10.1002/ajmg.a.31736]
</p>
</li>
<li>
<p class="mim-text-font">
Taddei, I., Morishima, M., Huynh, T., Lindsay, E. A.
<strong>Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge/del22q11 syndromes.</strong>
Proc. Nat. Acad. Sci. 98: 11428-11431, 2001.
[PubMed: 11562466]
[Full Text: https://doi.org/10.1073/pnas.201127298]
</p>
</li>
<li>
<p class="mim-text-font">
Toriello, H. V., Sharda, J. K., Beaumont, E. J.
<strong>Autosomal recessive syndrome of sacral and conotruncal developmental field defects (Kousseff syndrome).</strong>
Am. J. Med. Genet. 22: 357-360, 1985.
[PubMed: 4050868]
[Full Text: https://doi.org/10.1002/ajmg.1320220220]
</p>
</li>
<li>
<p class="mim-text-font">
Tsai, C.-H., Van Dyke, D. L., Feldman, G. L.
<strong>A child with velocardiofacial syndrome and del(4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype.</strong>
Am. J. Med. Genet. 82: 336-339, 1999.
[PubMed: 10051168]
</p>
</li>
<li>
<p class="mim-text-font">
Van Esch, H., Groenen, P., Fryns, J.-P., Van de Ven, W., Devriendt, K.
<strong>The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome.</strong>
Genet. Counsel. 10: 59-65, 1999.
[PubMed: 10191430]
</p>
</li>
<li>
<p class="mim-text-font">
Van Geet, C., Devriendt, K., Eyskens, B., Vermylen, J., Hoylaerts, M. F.
<strong>Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets.</strong>
Pediat. Res. 44: 607-611, 1998.
[PubMed: 9773854]
[Full Text: https://doi.org/10.1203/00006450-199810000-00023]
</p>
</li>
<li>
<p class="mim-text-font">
Van, L., Butcher, N. J., Costain, G., Ogura, L., Chow, E. W. C., Bassett, A. S.
<strong>Fetal growth and gestational factors as predictors of schizophrenia in 22q11.2 deletion syndrome.</strong>
Genet. Med. 18: 350-355, 2016.
[PubMed: 26087175]
[Full Text: https://doi.org/10.1038/gim.2015.84]
</p>
</li>
<li>
<p class="mim-text-font">
Vincent, M.-C., Heitz, F., Tricoire, J., Bourrouillou, G., Kuhlein, E., Rolland, M., Calvas, P.
<strong>22q deletion in DGS/VCFS monozygotic twins with discordant phenotypes.</strong>
Genet. Counsel. 10: 43-49, 1999.
[PubMed: 10191428]
</p>
</li>
<li>
<p class="mim-text-font">
Williams, M. A., Goldberg, R. B., Shprintzen, R. J.
<strong>Male-to-male transmission of the velo-cardio-facial syndrome: a case report and review of 60 cases.</strong>
J. Craniofac. Genet. Dev. Biol. 5: 175-180, 1985.
[PubMed: 4019731]
</p>
</li>
<li>
<p class="mim-text-font">
Williams, M. A., Shprintzen, R. J., Rakoff, S. J.
<strong>Adenoid hypoplasia in the velo-cardio-facial syndrome.</strong>
J. Craniofac. Genet. Dev. Biol. 7: 23-26, 1987.
[PubMed: 3597719]
</p>
</li>
<li>
<p class="mim-text-font">
Woodin, M., Wang, P. P., Aleman, D., McDonald-McGinn, D., Zackai, E., Moss, E.
<strong>Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion.</strong>
Genet. Med. 3: 34-39, 2001.
[PubMed: 11339375]
[Full Text: https://doi.org/10.1097/00125817-200101000-00008]
</p>
</li>
<li>
<p class="mim-text-font">
Worthington, S., Colley, A., Fagan, K., Dai, K., Lipson, A. H.
<strong>Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?</strong>
J. Med. Genet. 34: 79-82, 1997.
[PubMed: 9032655]
[Full Text: https://doi.org/10.1136/jmg.34.1.79]
</p>
</li>
<li>
<p class="mim-text-font">
Wraith, J. E., Super, M., Watson, G. H., Phillips, M.
<strong>Velo-cardio-facial syndrome presenting as holoprosencephaly.</strong>
Clin. Genet. 27: 408-410, 1985.
[PubMed: 3995791]
[Full Text: https://doi.org/10.1111/j.1399-0004.1985.tb02284.x]
</p>
</li>
<li>
<p class="mim-text-font">
Yagi, H., Furutani, Y., Hamada, H., Sasaki, T., Asakawa, S., Minoshima, S., Ichida, F., Joo, K., Kimura, M., Imamura, S., Kamatani, N., Momma, K., Takao, A., Nakazawa, M., Shimizu, N., Matsuoka, R.
<strong>Role of TBX1 in human del22q11.2 syndrome.</strong>
Lancet 362: 1366-1373, 2003.
[PubMed: 14585638]
[Full Text: https://doi.org/10.1016/s0140-6736(03)14632-6]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 06/04/2020<br>Ada Hamosh - updated : 05/06/2019<br>Ada Hamosh - updated : 10/14/2013<br>Ada Hamosh - updated : 11/7/2012<br>Ada Hamosh - updated : 10/4/2012<br>Ada Hamosh - updated : 12/14/2011<br>Cassandra L. Kniffin - updated : 11/29/2010<br>Ada Hamosh - updated : 4/28/2010<br>Cassandra L. Kniffin - updated : 3/10/2010<br>Ada Hamosh - updated : 7/28/2009<br>Kelly A. Przylepa - updated : 10/25/2007<br>Cassandra L. Kniffin - updated : 3/13/2007<br>John Logan Black, III - updated : 1/23/2007<br>George E. Tiller - updated : 1/16/2007<br>Cassandra L. Kniffin - updated : 12/7/2006<br>George E. Tiller - updated : 12/4/2006<br>Marla J. F. O&#x27;Neill - updated : 7/26/2006<br>Cassandra L. Kniffin - updated : 6/1/2006<br>John Logan Black, III - updated : 5/17/2006<br>Cassandra L. Kniffin - updated : 3/9/2006<br>John Logan Black, III - updated : 12/21/2005<br>Cassandra L. Kniffin - updated : 10/5/2005<br>Victor A. McKusick - updated : 12/23/2003<br>Victor A. McKusick - updated : 10/16/2003<br>Deborah L. Stone - updated : 5/29/2003<br>Ada Hamosh - updated : 2/27/2003<br>Victor A. McKusick - updated : 11/7/2002<br>Victor A. McKusick - updated : 9/16/2002<br>Deborah L. Stone - updated : 9/11/2002<br>George E. Tiller - updated : 5/9/2002<br>Ada Hamosh - updated : 4/30/2002<br>Sonja A. Rasmussen - updated : 3/7/2002<br>Ada Hamosh - updated : 2/13/2002<br>Ada Hamosh - updated : 1/29/2002<br>Ada Hamosh - updated : 1/9/2002<br>Victor A. McKusick - updated : 11/1/2001<br>Stylianos E. Antonarakis - updated : 3/6/2001<br>Ada Hamosh - updated : 2/6/2001<br>George E. Tiller - updated : 4/14/2000<br>Victor A. McKusick - updated : 1/14/2000<br>Wilson H. Y. Lo - updated : 9/22/1999<br>Wilson H. Y. Lo - updated : 8/12/1999<br>Wilson H. Y. Lo - updated : 8/12/1999<br>Sonja A. Rasmussen - updated : 5/12/1999<br>Victor A. McKusick - updated : 2/24/1999<br>Michael J. Wright - updated : 6/5/1998<br>Jennifer P. Macke - updated : 11/26/1997<br>Michael J. Wright - updated : 11/20/1997<br>Victor A. McKusick - updated : 6/12/1997<br>Moyra Smith - Updated : 5/22/1996
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/2/1986
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 11/19/2024<br>carol : 11/12/2020<br>alopez : 06/04/2020<br>carol : 02/13/2020<br>carol : 07/19/2019<br>alopez : 05/06/2019<br>alopez : 06/26/2018<br>carol : 03/03/2017<br>carol : 01/08/2016<br>carol : 1/7/2016<br>carol : 3/21/2014<br>alopez : 10/14/2013<br>alopez : 10/14/2013<br>alopez : 11/8/2012<br>terry : 11/7/2012<br>alopez : 10/4/2012<br>alopez : 1/4/2012<br>terry : 12/14/2011<br>alopez : 5/11/2011<br>wwang : 12/1/2010<br>ckniffin : 11/29/2010<br>carol : 7/1/2010<br>alopez : 4/29/2010<br>terry : 4/28/2010<br>wwang : 3/19/2010<br>ckniffin : 3/10/2010<br>ckniffin : 3/10/2010<br>carol : 8/13/2009<br>terry : 7/28/2009<br>alopez : 6/10/2009<br>terry : 5/19/2009<br>carol : 12/1/2008<br>terry : 9/26/2008<br>alopez : 2/28/2008<br>carol : 10/25/2007<br>wwang : 3/13/2007<br>carol : 1/23/2007<br>alopez : 1/17/2007<br>alopez : 1/17/2007<br>terry : 1/16/2007<br>wwang : 12/7/2006<br>wwang : 12/5/2006<br>terry : 12/4/2006<br>wwang : 9/18/2006<br>wwang : 8/1/2006<br>terry : 7/26/2006<br>wwang : 6/14/2006<br>ckniffin : 6/1/2006<br>wwang : 5/23/2006<br>terry : 5/17/2006<br>wwang : 3/16/2006<br>ckniffin : 3/9/2006<br>terry : 12/23/2005<br>carol : 12/21/2005<br>wwang : 10/12/2005<br>ckniffin : 10/5/2005<br>terry : 2/22/2005<br>carol : 2/12/2004<br>terry : 12/23/2003<br>cwells : 10/21/2003<br>terry : 10/16/2003<br>carol : 6/24/2003<br>carol : 5/29/2003<br>alopez : 3/4/2003<br>terry : 2/27/2003<br>mgross : 12/10/2002<br>tkritzer : 11/13/2002<br>terry : 11/7/2002<br>terry : 11/7/2002<br>carol : 9/16/2002<br>carol : 9/11/2002<br>cwells : 5/17/2002<br>cwells : 5/9/2002<br>alopez : 5/1/2002<br>terry : 4/30/2002<br>carol : 4/8/2002<br>carol : 3/8/2002<br>terry : 3/7/2002<br>alopez : 2/14/2002<br>terry : 2/13/2002<br>alopez : 1/31/2002<br>terry : 1/29/2002<br>alopez : 1/17/2002<br>terry : 1/9/2002<br>mcapotos : 11/20/2001<br>mcapotos : 11/9/2001<br>terry : 11/1/2001<br>carol : 9/13/2001<br>mgross : 3/6/2001<br>mgross : 3/6/2001<br>alopez : 2/26/2001<br>alopez : 2/22/2001<br>mcapotos : 2/12/2001<br>mcapotos : 2/9/2001<br>terry : 2/6/2001<br>alopez : 4/14/2000<br>terry : 4/14/2000<br>carol : 2/1/2000<br>terry : 1/14/2000<br>carol : 12/13/1999<br>carol : 9/22/1999<br>carol : 8/12/1999<br>carol : 8/12/1999<br>carol : 5/12/1999<br>carol : 5/12/1999<br>terry : 2/24/1999<br>terry : 7/29/1998<br>alopez : 6/17/1998<br>terry : 6/5/1998<br>carol : 5/8/1998<br>alopez : 12/5/1997<br>alopez : 12/3/1997<br>alopez : 12/3/1997<br>dholmes : 11/26/1997<br>dholmes : 11/26/1997<br>mark : 7/8/1997<br>mark : 6/16/1997<br>terry : 6/12/1997<br>carol : 5/22/1996<br>carol : 5/18/1996<br>mark : 12/11/1995<br>mark : 10/9/1995<br>mimadm : 6/7/1995<br>terry : 5/25/1995<br>carol : 4/11/1994<br>carol : 2/19/1993<br>carol : 1/19/1993
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
</div>
</div>
</div>
<div class="visible-print-block mim-footer" style="position: relative;">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
<br />
Printed: March 5, 2025
</div>
</div>
</div>
</div>
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
<div class="modal-dialog" role="document">
<div class="modal-content">
<div class="modal-header">
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">&times;</span></button>
<h4 class="modal-title" id="mimDonationPopupModalTitle">
OMIM Donation:
</h4>
</div>
<div class="modal-body">
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Dear OMIM User,
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
To ensure long-term funding for the OMIM project, we have diversified
our revenue stream. We are determined to keep this website freely
accessible. Unfortunately, it is not free to produce. Expert curators
review the literature and organize it to facilitate your work. Over 90%
of the OMIM's operating expenses go to salary support for MD and PhD
science writers and biocurators. Please join your colleagues by making a
donation now and again in the future. Donations are an important
component of our efforts to ensure long-term funding to provide you the
information that you need at your fingertips.
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Thank you in advance for your generous support, <br />
Ada Hamosh, MD, MPH <br />
Scientific Director, OMIM <br />
</p>
</div>
</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
Reference in a new issue View git blame Copy permalink