6791 lines
694 KiB
Text
6791 lines
694 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!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
|
|
|
|
- #100800 - ACHONDROPLASIA; ACH
|
|
|
|
|
|
- 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=100800"><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">#100800</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/100800"><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="#description">Description</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="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</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="#diagnosis">Diagnosis</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="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</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;">▼</div>
|
|
|
|
<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;">▼</div>
|
|
|
|
<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=ACHONDROPLASIA" 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://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=148&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/NBK1152/" 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://www.diseaseinfosearch.org/x/113" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/condition/achondroplasia" 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=100800[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=15" 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/5cd7c996-1841-45f8-a7c0-3c850618cee9/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;">►</div>
|
|
|
|
<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:4480" 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/100800" 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://omia.org/OMIA001703/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:4480" 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;">►</div>
|
|
|
|
<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:100800" 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.">
|
|
|
|
</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>SNOMEDCT:</strong> 86268005<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q77.4<br />
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 15<br />
|
|
|
|
|
|
<strong>DO:</strong> 4480<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>
|
|
100800
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ACHONDROPLASIA; ACH
|
|
|
|
</span>
|
|
</h3>
|
|
</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/4/34?start=-3&limit=10&highlight=34">
|
|
4p16.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Achondroplasia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/100800"> 100800 </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">
|
|
FGFR3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134934"> 134934 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/100800" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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/100800" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/100800" 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-limb dwarfism identifiable at birth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850171&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850171</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008921" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008921</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008921" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008921</a>]</span><br /> -
|
|
Mean male adult height, 131 cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863420&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863420</a>]</span><br /> -
|
|
Mean female height, 124 cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863421</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">
|
|
|
|
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Megalencephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9740002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9740002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2720434&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2720434</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span><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">
|
|
|
|
- Midface hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853242&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853242</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Midface_Retrusion-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><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">
|
|
|
|
- Recurrent otitis media in infancy and childhood <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863422</a>]</span><br /> -
|
|
Conductive hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44057004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44057004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018777&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018777</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</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">
|
|
|
|
- Low nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><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> Airways </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Upper airway obstruction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740852&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740852</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002781</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002781</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>
|
|
<span class="mim-font">
|
|
|
|
- Generalized joint laxity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836308&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836308</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002761</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002761</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skull </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Jugular bulb dehiscence (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810473&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810473</a>]</span><br /> -
|
|
Foramen magnum stenosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444879009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444879009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1535953&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1535953</a>, <a href="https://bioportal.bioontology.org/search?q=C1861217&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861217</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002677</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002677</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Lumbar kyphosis in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863423&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863423</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008414</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008414</a>]</span><br /> -
|
|
Exaggerated lumbar lordosis during childhood and adulthood <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863424&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863424</a>]</span><br /> -
|
|
Congenital spinal stenosis due to short pedicles, especially lumbar <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863425</a>]</span><br /> -
|
|
Progressive interpediculate narrowing in lumbar spine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863426&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863426</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Pelvis </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dysplastic ilium <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863427</a>]</span><br /> -
|
|
Narrow sacroiliac groove <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863428</a>]</span><br /> -
|
|
Flat rooted acetabulae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863429</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Limbs </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Bowing of legs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002979" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002979</a>]</span><br /> -
|
|
Rhizomelic shortening <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866730&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866730</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008905" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008905</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008905" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008905</a>]</span><br /> -
|
|
Short femoral neck <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836184&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836184</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100864" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100864</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100864" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100864</a>]</span><br /> -
|
|
Metaphyseal flaring <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850135&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850135</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003015</a>]</span><br /> -
|
|
Limited elbow and hip extension <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867495&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867495</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Hands </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Brachydactyly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43476002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43476002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221357&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221357</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001156" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001156</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001156" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001156</a>]</span><br /> -
|
|
Trident hand <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249755001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249755001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004060" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004060</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004060" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004060</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=e45857776714e012fdea844fb57c5837" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Hand,Trident-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=e45857776714e012fdea844fb57c5837" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><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">
|
|
|
|
- Hydrocephalus, occasional <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863418</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br /> -
|
|
Hypotonia in infancy and early childhood <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863419&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863419</a>]</span><br /> -
|
|
Brain stem compression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5582005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5582005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25816005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25816005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270680&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270680</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002512" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002512</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002512" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002512</a>]</span><br /> -
|
|
Delayed motor development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</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">
|
|
|
|
- Autosomal dominant with complete penetrance<br /> -
|
|
80% cases new mutations<br /> -
|
|
99+% of the mutations are FGFR3, G380R (<a href="/entry/134934#0001">134934.0001</a>)<br /> -
|
|
Paternal age effect<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">
|
|
|
|
- Caused by mutation in the fibroblast growth factor receptor-3 gene (FGFR3, <a href="/entry/134934#0001">134934.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ 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">▼</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 <span class='glyphicon glyphicon-plus-sign'></span> 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 achondroplasia (ACH) is caused by heterozygous mutation in the fibroblast growth factor receptor-3 gene (FGFR3; <a href="/entry/134934">134934</a>) on chromosome 4p16.3.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Achondroplasia (ACH) is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by <a href="#7" class="mim-tip-reference" title="Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A. <strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong> Am. J. Hum. Genet. 56: 368-373, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847369</a>]" pmid="7847369">Bellus et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7847369" 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="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</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>Whereas many conditions that cause short stature have inappropriately been called achondroplasia in the past, the phenotype of this osteochondrodysplasia is so distinctive and so easily identified clinically and radiologically at birth that confusion should not occur. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Hyperextensibility of most joints, especially the knees, is common, but extension and rotation are limited at the elbow. A thoracolumbar gibbus is typically present at birth, but usually gives way to exaggerated lumbar lordosis when the child begins to ambulate. Mild to moderate hypotonia is common, and motor milestones are usually delayed. Intelligence is normal unless hydrocephalus or other central nervous system complications arise. In 13 achondroplastic infants, <a href="#38" class="mim-tip-reference" title="Hecht, J. T., Thompson, N. M., Weir, T., Patchell, L., Horton, W. A. <strong>Cognitive and motor skills in achondroplastic infants: neurologic and respiratory correlates.</strong> Am. J. Med. Genet. 41: 208-211, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1785636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1785636</a>] [<a href="https://doi.org/10.1002/ajmg.1320410215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1785636">Hecht et al. (1991)</a> found that cognitive development was average and did not correlate with motor development which typically was delayed. It was noteworthy that reduced mental capacity correlated with evidence of respiratory dysfunction detected by polysomnography. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1785636" 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>In children, caudad narrowing of the interpediculate distance, rather than the normal caudad widening, and a notchlike sacroiliac groove are typical radiologic features. Also in children, epiphyseal ossification centers show a circumflex or chevron seat on the metaphysis. Limb shortening is especially striking in the proximal segments, e.g., the humerus; hence the description rhizomelic ('root limb'). The radiologic features of true achondroplasia and much concerning the natural history of the condition were presented by <a href="#56" class="mim-tip-reference" title="Langer, L. O., Jr., Baumann, P. A., Gorlin, R. J. <strong>Achondroplasia.</strong> Am. J. Roentgen. Radium Ther. Nucl. Med. 100: 12-26, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6023888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6023888</a>] [<a href="https://doi.org/10.2214/ajr.100.1.12" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6023888">Langer et al. (1967)</a> on the basis of a study of 101 cases and by <a href="#35" class="mim-tip-reference" title="Hall, J. G. <strong>The natural history of achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong> New York: Plenum Press (pub.) 1988. Pp. 3-10."None>Hall (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6023888" 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>True megalencephaly occurs in achondroplasia and has been speculated to indicate effects of the gene other than those on the skeleton alone (<a href="#17" class="mim-tip-reference" title="Dennis, J. P., Rosenberg, H. S., Alvord, E. C., Jr. <strong>Megalencephaly, internal hydrocephalus and other neurological aspects of achondroplasia.</strong> Brain 84: 427-445, 1961.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13885465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13885465</a>] [<a href="https://doi.org/10.1093/brain/84.3.427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13885465">Dennis et al., 1961</a>). Disproportion between the base of the skull and the brain results in internal hydrocephalus in some cases. The hydrocephalus may be caused by increased intracranial venous pressure due to stenosis of the sigmoid sinus at the level of the narrowed jugular foramina (<a href="#83" class="mim-tip-reference" title="Pierre-Kahn, A., Hirsch, J. F., Renier, D., Metzger, J., Maroteaux, P. <strong>Hydrocephalus and achondroplasia: a study of 25 observations.</strong> Child's Brain 7: 205-219, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7438842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7438842</a>]" pmid="7438842">Pierre-Kahn et al., 1980</a>). <a href="#34" class="mim-tip-reference" title="Hall, J. G., Horton, W., Kelly, T., Scott, C. I. <strong>Head growth in achondroplasia: use of ultrasound studies. (Letter)</strong> Am. J. Med. Genet. 13: 105, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7137217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7137217</a>] [<a href="https://doi.org/10.1002/ajmg.1320130116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7137217">Hall et al. (1982)</a> pointed out that the large head of the achondroplastic fetus creates an increased risk of intracranial bleeding during delivery. They recommended that in the management of achondroplastic infants ultrasonography be done at birth and at 2, 4, and 6 months of age to establish ventricular size, the presence or absence of hydrocephalus, and possible intracranial bleed. They stated the impression that some achondroplasts have only megalencephaly, others have true communicating hydrocephalus, and yet others have dilated ventricles without hydrocephalus. <a href="#69" class="mim-tip-reference" title="Nelson, F. W., Hecht, J. T., Horton, W. A., Butler, I. J., Goldie, W. D., Miner, M. <strong>Neurological basis of respiratory complications in achondroplasia.</strong> Ann. Neurol. 24: 89-93, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3415202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3415202</a>] [<a href="https://doi.org/10.1002/ana.410240117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3415202">Nelson et al. (1988)</a> concluded that brainstem compression is common in achondroplasia and may account in part for the abnormal respiratory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7137217+7438842+13885465+3415202" 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="Pauli, R. M., Scott, C. I., Wassman, E. R., Jr., Gilbert, E. F., Leavitt, L. A., Ver Hoeve, J., Hall, J. G., Partington, M. W., Jones, K. L., Sommer, A., Feldman, W., Langer, L. O., Rimoin, D. L., Hecht, J. T., Lebovitz, R. <strong>Apnea and sudden unexpected death in infants with achondroplasia.</strong> J. Pediat. 104: 342-348, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6707788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6707788</a>] [<a href="https://doi.org/10.1016/s0022-3476(84)81092-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6707788">Pauli et al. (1984)</a> focused attention on the risk of sudden unexpected death in infants with achondroplasia. While uncontrolled and retrospective, their study demonstrated an excess of deaths in the first year of life, most or all of which were attributable to abnormalities at the craniocervical junction. <a href="#36" class="mim-tip-reference" title="Hecht, J. T., Francomano, C. A., Horton, W. A., Annegers, J. F. <strong>Mortality in achondroplasia.</strong> Am. J. Hum. Genet. 41: 454-464, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3631079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3631079</a>]" pmid="3631079">Hecht et al. (1987)</a> showed that the excess risk of death in infants with achondroplasia may approach 7.5%, largely because of cervical cord compression. <a href="#76" class="mim-tip-reference" title="Pauli, R. M., Horton, V. K., Glinski, L. P., Reiser, C. A. <strong>Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia.</strong> Am. J. Hum. Genet. 56: 732-744, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7887429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7887429</a>]" pmid="7887429">Pauli et al. (1995)</a> performed a prospective assessment of risk for cervical medullary-junction compression in 53 infants, 5 of whom were judged to have sufficient craniocervical junction compression to require surgical decompression. Intraoperative observation showed marked abnormality of the cervical spinal cord, and all operated-on children showed marked improvement of neurologic function. The best predictors of need for suboccipital decompression included lower-limb hyperreflexia or clonus on examination, central hypopnea demonstrated by polysomnography, and foramen magnum measures below the mean for children with achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7887429+3631079+6707788" 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="Lachman, R. S. <strong>Neurologic abnormalities in the skeletal dysplasias: a clinical and radiological perspective.</strong> Am. J. Med. Genet. 69: 33-43, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9066881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9066881</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19970303)69:1<33::aid-ajmg7>3.0.co;2-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9066881">Lachman (1997)</a> reviewed the neurologic abnormalities in the skeletal dysplasias from a clinical and radiologic perspective. Three important major groups were identified: (i) achondroplasia (cranio-cervical junction problems in infancy, spinal stenosis, and neurogenic claudication in adulthood); (ii) type II collagenopathies (upper cervical spine anatomic and functional problems); and (iii) craniotubular and sclerosing bone dysplasias (osseous overgrowth with foraminal obstruction problems). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9066881" 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 detect myelopathy, <a href="#9" class="mim-tip-reference" title="Boor, R., Fricke, G., Bruhl, K., Spranger, J. <strong>Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia.</strong> Europ. J. Pediat. 158: 662-667, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10445347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10445347</a>] [<a href="https://doi.org/10.1007/s004310051172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10445347">Boor et al. (1999)</a> recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia. In addition to the conventional technique, they employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the craniocervical junction. The findings were correlated with the clinical status and MRI results. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia, and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10445347" 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="#37" class="mim-tip-reference" title="Hecht, J. T., Hood, O. J., Schwartz, R. J., Hennessey, J. C., Bernhardt, B. A., Horton, W. A. <strong>Obesity in achondroplasia.</strong> Am. J. Med. Genet. 31: 597-602, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3228140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3228140</a>] [<a href="https://doi.org/10.1002/ajmg.1320310314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3228140">Hecht et al. (1988)</a> reviewed the subject of obesity in achondroplasia, concluding that it is a major problem which, whatever its underlying cause, aggravates the morbidity associated with lumbar stenosis and contributes to the nonspecific joint problems and to the possible early cardiovascular mortality in this condition. Using data about 409 Caucasian patients with achondroplasia from different countries (1,147 observations), <a href="#51" class="mim-tip-reference" title="Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I. <strong>Standard weight for height curves in achondroplasia.</strong> Am. J. Med. Genet. 62: 255-261, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882783</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882783">Hunter et al. (1996)</a> developed weight for height (W/H) curves for these patients. They showed that to a height of about 75 cm, the mean W/H curves are virtually identical for normal and achondroplastic children. After this height, the W/H curves for achondroplastic patients rise above those for the general population. <a href="#51" class="mim-tip-reference" title="Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I. <strong>Standard weight for height curves in achondroplasia.</strong> Am. J. Med. Genet. 62: 255-261, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882783</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882783">Hunter et al. (1996)</a> contended that the best estimation of weight excess for achondroplastic patients aged 3 to 6 years is given by the Quetelet index, whereas that for patients aged 6 to 18 years is the Rohrer index. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8882783+3228140" 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>Homozygosity for the achondroplasia gene results in a severe disorder of the skeleton with radiologic changes qualitatively somewhat different from those of the usual heterozygous achondroplasia; early death results from respiratory embarrassment from the small thoracic cage and neurologic deficit from hydrocephalus (<a href="#32" class="mim-tip-reference" title="Hall, J. G., Dorst, J. P., Taybi, H., Scott, C. I., Jr., Langer, L. O., Jr., McKusick, V. A. <strong>Two probable cases of homozygosity for the achondroplasia gene.</strong> Birth Defects Orig. Art. Ser. V(4): 24-34, 1969."None>Hall et al., 1969</a>). <a href="#118" class="mim-tip-reference" title="Yang, S. S., Corbett, D. P., Brough, A. J., Heidelberger, K. P., Bernstein, J. <strong>Upper cervical myelopathy in achondroplasia.</strong> Am. J. Clin. Path. 68: 68-72, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/868806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">868806</a>] [<a href="https://doi.org/10.1093/ajcp/68.1.68" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="868806">Yang et al. (1977)</a> reported upper cervical myelopathy in a homozygote. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=868806" 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="#46" class="mim-tip-reference" title="Horton, W. A., Hood, O. J., Machado, M. A., Campbell, D. <strong>Growth plate cartilage studies in achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong> New York: Plenum Press (pub.) 1988. Pp. 81-89."None>Horton et al. (1988)</a> found that the epiphyseal and growth plate cartilages have a normal appearance histologically, and the major matrix constituents exhibit a normal distribution by immunostaining; however, morphometric investigations have indicated that the growth plate is shorter than normal and that the shortening is greater in homozygous than in heterozygous achondroplasia, suggesting a gene dosage effect. <a href="#98" class="mim-tip-reference" title="Stanescu, R., Stanescu, V., Maroteaux, P. <strong>Homozygous achondroplasia: morphologic and biochemical study of cartilage.</strong> Am. J. Med. Genet. 37: 412-421, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2260574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2260574</a>] [<a href="https://doi.org/10.1002/ajmg.1320370323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2260574">Stanescu et al. (1990)</a> reported histochemical, immunohistochemical, electron microscopic, and biochemical studies on upper tibial cartilage from a case of homozygous achondroplasia. No specific abnormality was defined. <a href="#2" class="mim-tip-reference" title="Aterman, K., Welch, J. P., Taylor, P. G. <strong>Presumed homozygous achondroplasia: a review and report of a further case.</strong> Path. Res. Pract. 178: 27-39, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6359101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6359101</a>] [<a href="https://doi.org/10.1016/S0344-0338(83)80082-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6359101">Aterman et al. (1983)</a> expressed puzzlement at the striking histologic changes in homozygous achondroplasia despite the virtual absence of changes in the heterozygote. They pointed out that histologic studies in the heterozygote at a few weeks or months of age have not been done. They suggested that because of similarities between what they called PHA (presumed homozygous achondroplasia) and thanatophoric dwarfism (<a href="/entry/187600">187600</a>), some cases of the latter condition may be due to a particularly severe mutation at the achondroplasia locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6359101+2260574" 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="#120" class="mim-tip-reference" title="Young, I. D., Ruggins, N. R., Somers, J. M., Zuccollo, J. M., Rutter, N. <strong>Lethal skeletal dysplasia owing to a double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita.</strong> J. Med. Genet. 29: 831-833, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1453438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1453438</a>] [<a href="https://doi.org/10.1136/jmg.29.11.831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1453438">Young et al. (1992)</a> described lethal short-limb dwarfism in the offspring of a father with spondyloepiphyseal dysplasia congenita (SEDC; <a href="/entry/183900">183900</a>) and a mother with achondroplasia. <a href="#120" class="mim-tip-reference" title="Young, I. D., Ruggins, N. R., Somers, J. M., Zuccollo, J. M., Rutter, N. <strong>Lethal skeletal dysplasia owing to a double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita.</strong> J. Med. Genet. 29: 831-833, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1453438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1453438</a>] [<a href="https://doi.org/10.1136/jmg.29.11.831" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1453438">Young et al. (1992)</a> suggested that the infant was a double heterozygote for the 2 dominant genes rather than a compound heterozygote. It was considered unlikely that SEDC and achondroplasia are allelic because of the evidence that most, if not all, cases of SEDC result from mutation in the type II collagen gene (COL2A1; <a href="/entry/120140">120140</a>), whereas this gene has been excluded as the site of the mutation in achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1453438" 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>Evidence that hypochondroplasia (<a href="/entry/146000">146000</a>) can be caused by an allele at the achondroplasia locus came from observations of a presumed genetic compound in the offspring of an achondroplastic father and a hypochondroplastic mother who exhibited growth deficiency and radiographic abnormalities of the skeleton that were much more severe than those typically seen in achondroplasia (<a href="#63" class="mim-tip-reference" title="McKusick, V. A., Kelly, T. E., Dorst, J. P. <strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong> J. Med. Genet. 10: 11-16, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4697848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4697848</a>] [<a href="https://doi.org/10.1136/jmg.10.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4697848">McKusick et al., 1973</a>; <a href="#97" class="mim-tip-reference" title="Sommer, A., Young-Wee, T., Frye, T. <strong>Achondroplasia-hypochondroplasia complex.</strong> Am. J. Med. Genet. 26: 949-957, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3591840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3591840</a>] [<a href="https://doi.org/10.1002/ajmg.1320260426" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3591840">Sommer et al., 1987</a>) and somewhat less severe than those of the ACH homozygote. <a href="#49" class="mim-tip-reference" title="Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T. <strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong> Am. J. Med. Genet. 84: 396-400, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360392</a>]" pmid="10360392">Huggins et al. (1999)</a> reported an 8-month-old girl with achondroplasia/hypochondroplasia whose father had the G380R achondroplasia mutation (<a href="/entry/134934#0001">134934.0001</a>) in the FGFR3 gene and whose mother had the N450K hypochondroplasia mutation (<a href="/entry/134934#0010">134934.0010</a>). <a href="#12" class="mim-tip-reference" title="Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D. <strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong> Am. J. Med. Genet. 84: 401-405, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360393</a>]" pmid="10360393">Chitayat et al. (1999)</a> simultaneously reported an infant boy with achondroplasia/hypochondroplasia whose mother had the G380R mutation and whose father had the N450K mutation. Molecular analysis confirmed the compound heterozygosity of both children, who displayed an intermediate phenotype that was more severe than either condition in the heterozygous state but less severe than homozygous ACH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4697848+10360393+10360392+3591840" 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>In a presentation of adult genetic skeletal dysplasias found in the Museum of Pathological Anatomy in Vienna, <a href="#5" class="mim-tip-reference" title="Beighton, P., Sujansky, E., Patzak, B., Portele, K. A. <strong>Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.</strong> Am. J. Med. Genet. 47: 843-847, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8279481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8279481</a>] [<a href="https://doi.org/10.1002/ajmg.1320470609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8279481">Beighton et al. (1993)</a> pictured the skeleton of a 61-year-old man with achondroplasia who died of transverse myelitis. <a href="#86" class="mim-tip-reference" title="Randolph, L. M., Shohat, M., Miller, D., Lachman, R., Rimoin, D. L. <strong>Achondroplasia with ankylosing spondylitis.</strong> Am. J. Med. Genet. 31: 117-121, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3223492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3223492</a>] [<a href="https://doi.org/10.1002/ajmg.1320310113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3223492">Randolph et al. (1988)</a> reported an achondroplastic patient who developed classic ankylosing spondylitis (<a href="/entry/106300">106300</a>). There is no fundamental connection between the 2 disorders. The importance of the observation is mainly to indicate that back problems in achondroplasts can be due to causes other than the underlying disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3223492+8279481" 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="#50" class="mim-tip-reference" title="Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr. <strong>Medical complications of achondroplasia: a multicentre patient review.</strong> J. Med. Genet. 35: 705-712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>] [<a href="https://doi.org/10.1136/jmg.35.9.705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733026">Hunter et al. (1998)</a> presented data from a multicenter study of 193 individuals with achondroplasia. They found that 89.4% of children had at least one episode of otitis media within the first 2 years of life; 24 of 99 children who had otitis media in the first year of life had several infections. All were observed to have chronic otitis media; 78.3% of individuals required the insertion of ventilation tubes at some point in their lives. Thirty of 85 patients aged 1 to 2 years and 26 of 70 patients aged 2 to 3 years had received at least one set of ventilation tubes. A degree of conductive hearing loss was found in 38.3% of individuals at sometime in their lives, the majority of these being found after 4 years of age Tonsillectomy was performed in 38.8% of individuals, with cumulative rates of 8.8% within the first 4 years of life and 25% by age 8 years. Speech delay was found in 18.6% of individuals, and 10.9% had articulation problems; only 9.5% of these individuals received speech therapy. Orthodontic problems were found in 53.8% of individuals; only 3.2% of these individuals presented within the first 10 years of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733026" 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="#50" class="mim-tip-reference" title="Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr. <strong>Medical complications of achondroplasia: a multicentre patient review.</strong> J. Med. Genet. 35: 705-712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>] [<a href="https://doi.org/10.1136/jmg.35.9.705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733026">Hunter et al. (1998)</a> found that 10.5% of individuals had a ventricular shunt placed; all but one of these procedures were done in the preteenage years. Cervicomedullary decompression surgery had been performed in 6.8% of children by 4 years of age; however, this procedure was also performed in a number of older children, teenagers, and adults, with a total of 16.5% of individuals having this type of surgery. Apnea was reported in 10.9% of individuals by age 4 years and 16.1% of individuals overall. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733026" 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="#50" class="mim-tip-reference" title="Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr. <strong>Medical complications of achondroplasia: a multicentre patient review.</strong> J. Med. Genet. 35: 705-712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>] [<a href="https://doi.org/10.1136/jmg.35.9.705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733026">Hunter et al. (1998)</a> defined tibial bowing as a distance of greater than 5 cm between the knees, with the legs straight and ankles apposed. Using these criteria, they found that 9.7% of individuals had tibial bowing by age 5 years. This continued to develop throughout childhood and into adult life, with a total of 41.6% of individuals being affected at some time. Tibial osteotomy had been performed on 21.6% of these individuals. By age 10 years, 8.9% of individuals had neurologic signs in the leg; however, by the sixth decade, 77.9% of individuals had these signs. A total of 24.1% had surgery for spinal stenosis, with an additional 18% in whom the diagnosis was made but surgery had not been performed. A majority of these surgeries were performed in individuals over 40 years of age. <a href="#50" class="mim-tip-reference" title="Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr. <strong>Medical complications of achondroplasia: a multicentre patient review.</strong> J. Med. Genet. 35: 705-712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>] [<a href="https://doi.org/10.1136/jmg.35.9.705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733026">Hunter et al. (1998)</a> concluded that middle ear disease with its attendant risk of hearing loss was more frequent than previously reported, and that while a significant number of patients with achondroplasia experience delayed speech, only a minority receive speech therapy. The rate of early cervicomedullary decompression was comparable to the previously reported series, but an equivalent proportion of patients require such intervention beyond childhood. <a href="#50" class="mim-tip-reference" title="Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr. <strong>Medical complications of achondroplasia: a multicentre patient review.</strong> J. Med. Genet. 35: 705-712, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>] [<a href="https://doi.org/10.1136/jmg.35.9.705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9733026">Hunter et al. (1998)</a> also concluded that a significant number of patients have neurologic complaints by their teenage years and that this becomes a majority in adulthood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733026" 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="#104" class="mim-tip-reference" title="Tasker, R. C., Dundas, I., Laverty, A., Fletcher, M., Lane, R., Stocks, J. <strong>Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study.</strong> Arch. Dis. Child. 79: 99-108, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9797588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9797588</a>] [<a href="https://doi.org/10.1136/adc.79.2.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9797588">Tasker et al. (1998)</a> characterized cardiorespiratory and sleep dysfunction in 17 patients with achondroplasia referred to Great Ormond Street Hospital for Children, London. Three distinct etiologic groups were identified: group 1 had a mild degree of midfacial hypoplasia resulting in relative adenotonsillar hypertrophy; group 2 had jugular foramen stenosis resulting in muscular upper airway obstruction and progressive hydrocephalus due to jugular venous hypertension; and group 3 had muscular upper airway obstruction without hydrocephalus resulting from hypoglossal canal stenosis with or without foramen magnum compression. In addition, gastroesophageal reflux, which tended to occur in group 3 patients, was identified as a significant factor in the development of airway disease. Group 1 patients had obstructive sleep apnea only, and showed marked symptomatic improvement following adenotonsillectomy. Group 2 patients had central apnea responsive to surgical treatment of their hydrocephalus; obstructive sleep apnea in this group did not appear to respond to adenotonsillectomy, but to nocturnal continuous positive airway pressure. Group 3 patients had progressive cor pulmonale, obstructive and central sleep apnea, and gastroesophageal reflux with small airway pathology requiring multiple treatment modalities including foramen magnum decompression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9797588" 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>In 4 (3.2%) of 126 children with achondroplasia undergoing periodic evaluations at a bone dysplasia clinic, <a href="#77" class="mim-tip-reference" title="Pauli, R. M., Modaff, P. <strong>Jugular bulb dehiscence in achondroplasia.</strong> Int. J. Pediat. Otorhinolaryng. 48: 169-174, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10375043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10375043</a>] [<a href="https://doi.org/10.1016/s0165-5876(99)00033-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10375043">Pauli and Modaff (1999)</a> identified a right-sided temporal bone abnormality involving absence of a roof over the jugular bulb, with bulging of the bulb into the middle ear cavity. In 2 patients, dark bluish-gray discoloration behind the tympanic membrane was noted, and temporal bone CT scan confirmed the presence of unilateral jugular bulb dehiscence. In a third patient, a large dehiscent jugular bulb was observed during exploratory tympanotomy; in a fourth patient, after brisk bleeding during attempted myringotomy and tube placement, CT scan demonstrated the absence of the bony covering of the jugular bulb. Jugular bulb dehiscence was suspected in a fifth patient with dark bluish discoloration behind the inferior quarter of the tympanic membrane, but confirmatory studies had not been performed at the time of the report. <a href="#77" class="mim-tip-reference" title="Pauli, R. M., Modaff, P. <strong>Jugular bulb dehiscence in achondroplasia.</strong> Int. J. Pediat. Otorhinolaryng. 48: 169-174, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10375043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10375043</a>] [<a href="https://doi.org/10.1016/s0165-5876(99)00033-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10375043">Pauli and Modaff (1999)</a> noted that dehiscence of the jugular bulb is of clinical relevance, particularly in regard to difficult-to-control bleeding at myringotomy, and is associated with otherwise unexplained hearing loss, tinnitus, and self-audible bruits in children with achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10375043" 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="#88" class="mim-tip-reference" title="Reynolds, K. K., Modaff, P., Pauli, R. M. <strong>Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia.</strong> Am. J. Med. Genet. 101: 40-45, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343336</a>] [<a href="https://doi.org/10.1002/ajmg.1307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343336">Reynolds et al. (2001)</a> retrospectively reviewed clinical and computed tomographic data in 71 infants with achondroplasia. They found no correlation between infantile hypotonia and foramen magnum size. These results suggested that there is no direct relationship and that foraminal size does not affect severity of hypotonia. They concluded that the only plausible explanation for the infantile hypotonia of achondroplasia is a primary effect of the causative mutation in FGFR3 (<a href="/entry/134934">134934</a>), which is expressed in brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343336" 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="#107" class="mim-tip-reference" title="Van Esch, H., Fryns, J. P. <strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong> Genet. Counsel. 15: 375-377, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15517832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15517832</a>]" pmid="15517832">Van Esch and Fryns (2004)</a> described acanthosis nigricans in a 9-year-old boy with achondroplasia due to the classic gly380-to-arg mutation (<a href="/entry/134934#0001">134934.0001</a>) in FGFR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15517832" 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="#117" class="mim-tip-reference" title="Wynn, J., King, T. M., Gambello, M. J., Waller, D. K., Hecht, J. T. <strong>Mortality in achondroplasia study: a 42-year follow-up.</strong> Am. J. Med. Genet. 143A: 2502-2511, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17879967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17879967</a>] [<a href="https://doi.org/10.1002/ajmg.a.31919" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17879967">Wynn et al. (2007)</a> reported a 42-year follow-up study of mortality in achondroplasia. The study included 718 achondroplasia individuals from an earlier mortality study by <a href="#36" class="mim-tip-reference" title="Hecht, J. T., Francomano, C. A., Horton, W. A., Annegers, J. F. <strong>Mortality in achondroplasia.</strong> Am. J. Hum. Genet. 41: 454-464, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3631079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3631079</a>]" pmid="3631079">Hecht et al. (1987)</a> and 75 additional achondroplasia individuals. Rates of death were similar across the entire follow-up period. The overall mortality and age-specific mortality at all ages remained significantly increased. Accidental and neurologic disease-related deaths were increased in adults. Heart disease-related mortality, between ages 25 and 35, was more than 10 times higher than in the general population. Overall survival and the average life expectancy in this ACH population were decreased by 10 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17879967+3631079" 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">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Achondroplasia is inherited as an autosomal dominant with essentially complete penetrance. About seven-eighths of cases are the result of new mutation, there being a considerable reduction of effective reproductive fitness.</p><p>Paternal age effect on mutation was noted by <a href="#79" class="mim-tip-reference" title="Penrose, L. S. <strong>Parental age and mutation.</strong> Lancet 266: 312-313, 1955. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13243724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13243724</a>] [<a href="https://doi.org/10.1016/s0140-6736(55)92305-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13243724">Penrose (1955)</a>. <a href="#101" class="mim-tip-reference" title="Stoll, C., Roth, M.-P., Bigel, P. <strong>A reexamination of parental age effect on the occurrence of new mutations for achondroplasia. In: Papadatos, C. J.; Bartsocas, C. S. (eds.): Skeletal Dysplasias.</strong> New York: Alan R. Liss (pub.) 1982. Pp. 419-426."None>Stoll et al. (1982)</a> reported advanced paternal age in sporadic cases ascertained through the French counterpart of LPA (Little People of America), APPT (Association des Personnes de Petite Taille). <a href="#105" class="mim-tip-reference" title="Thompson, J. N., Jr., Schaefer, G. B., Conley, M. C., Mascie-Taylor, C. G. N. <strong>Achondroplasia and parental age. (Letter)</strong> New Eng. J. Med. 314: 521-522, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3945286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3945286</a>] [<a href="https://doi.org/10.1056/nejm198602203140820" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3945286">Thompson et al. (1986)</a> found that, on average, the severity of achondroplasia tends to be reduced with increasing parental age. It is doubtful that a recessive form of achondroplasia, indistinguishable from the dominant form, exists. Documentation of the diagnosis is inadequate in most reports of possible recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13243724+3945286" 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="#106" class="mim-tip-reference" title="Tiemann-Boege, I., Navidi, W., Grewal, R., Cohn, D., Eskenazi, B., Wyrobek, A. J., Arnheim, N. <strong>The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.</strong> Proc. Nat. Acad. Sci. 99: 14952-14957, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12397172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12397172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12397172[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.232568699" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12397172">Tiemann-Boege et al. (2002)</a> performed direct molecular measurement of germline mutation frequency in sperm to test the hypothesis of paternal age effect on mutation. Using sperm DNA from donors of different ages, they determined the frequency of the 1138G-A mutation in the FGFR3 gene (<a href="/entry/134934#0001">134934.0001</a>) that causes achondroplasia. The magnitude of the increase in mutation frequency with age was insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives were considered to explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and were inefficiently detected by the PCR assay used in the study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12397172" 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="Cohn, S., Weinberg, A. <strong>Identical hydrocephalic achondroplastic twins. Subsequent delivery of single sibling with same abnormality.</strong> Am. J. Obstet. Gynec. 72: 1346-1348, 1956.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13372616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13372616</a>] [<a href="https://doi.org/10.1016/0002-9378(56)90797-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13372616">Cohn and Weinberg (1956)</a> reported affected twins with an affected sib. (This may have been achondrogenesis, e.g., <a href="/entry/200600">200600</a>.) <a href="#11" class="mim-tip-reference" title="Chiari, H. <strong>Ueber familiaere Chondrodystrophia foetalis.</strong> Muench. Med. Wschr. 60: 248-249, 1913."None>Chiari (1913)</a> reported affected half sibs whose father had achondroplasia. Two first cousins, whose mothers were average-statured sisters, had undoubted achondroplasia (<a href="#110" class="mim-tip-reference" title="Wadia, R. <strong>Achondroplasia in two first cousins.</strong> Birth Defects Orig. Art. Ser. V(4): 227-230, 1969."None>Wadia, 1969</a>). Most dominants show sufficient variability to account for observations such as these on the basis of reduced penetrance but such is not the case with achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13372616" 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>Gonadal mosaicism (or spermatogonial mutation) is a possible explanation for affected sibs from normal parents. <a href="#10" class="mim-tip-reference" title="Bowen, P. <strong>Achondroplasia in two sisters with normal parents.</strong> Birth Defects Orig. Art. Ser. X(12): 31-36, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4461062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4461062</a>]" pmid="4461062">Bowen (1974)</a> described a possible instance of gonadal mosaicism; 2 daughters of normal parents had achondroplasia. One of the daughters had 2 children, one of whom was also achondroplastic. <a href="#30" class="mim-tip-reference" title="Fryns, J. P., Kleczkowska, A., Verresen, H., van den Berghe, H. <strong>Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents.</strong> Clin. Genet. 24: 156-158, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6627718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6627718</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1983.tb02232.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6627718">Fryns et al. (1983)</a> reported 3 achondroplastic sisters born to normal parents. <a href="#82" class="mim-tip-reference" title="Philip, N., Auger, M., Mattei, J. F., Giraud, F. <strong>Achondroplasia in sibs of normal parents.</strong> J. Med. Genet. 25: 857-859, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3236371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3236371</a>] [<a href="https://doi.org/10.1136/jmg.25.12.857" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3236371">Philip et al. (1988)</a> described the case of a man who had 3 daughters with classic achondroplasia, by 2 different women. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6627718+3236371+4461062" 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="Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B. <strong>Germline and somatic mosaicism in achondroplasia.</strong> J. Med. Genet. 37: 956-958, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186939</a>] [<a href="https://doi.org/10.1136/jmg.37.12.956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11186939">Henderson et al. (2000)</a> reported sibs with achondroplasia born to average-statured parents. Both children had the 1138G-C causal mutation (<a href="/entry/134934#0002">134934.0002</a>); this was also found in 28% of the unaffected mother's peripheral leukocytes. The authors therefore hypothesized that she was a germline as well as somatic mosaic for this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186939" 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="#96" class="mim-tip-reference" title="Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A. <strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong> J. Med. Genet. 37: 958-959, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186940</a>] [<a href="https://doi.org/10.1136/jmg.37.12.958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11186940">Sobetzko et al. (2000)</a> also reported achondroplasia in a brother and sister with unaffected parents. The sibs shared the classic 1138G-A mutation (<a href="/entry/134934#0001">134934.0001</a>) and also shared a 4p haplotype derived from the unaffected father. Paternal sperm was not available, and evidence of gonadal mosaicism could not be substantiated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186940" 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>Affected cousins could be due to the coincidence of 2 independent mutations. Such was probably the case, in McKusick's opinion, in the second cousins once removed reported by <a href="#25" class="mim-tip-reference" title="Fitzsimmons, J. S. <strong>Familial recurrence of achondroplasia.</strong> Am. J. Med. Genet. 22: 609-613, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4061493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4061493</a>] [<a href="https://doi.org/10.1002/ajmg.1320220320" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4061493">Fitzsimmons (1985)</a>. <a href="#87" class="mim-tip-reference" title="Reiser, C. A., Pauli, R. M., Hall, J. G. <strong>Achondroplasia: unexpected familial recurrence.</strong> Am. J. Med. Genet. 19: 245-250, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6507475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6507475</a>] [<a href="https://doi.org/10.1002/ajmg.1320190206" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6507475">Reiser et al. (1984)</a> reviewed 6 families with unexpected familial recurrence and hypothesized that these recurrences were simply the result of 2 independent chance events. <a href="#18" class="mim-tip-reference" title="Dodinval, P., Le Marec, B. <strong>Genetic counselling in unexpected familial recurrence of achondroplasia.</strong> Am. J. Med. Genet. 28: 949-954, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3688033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3688033</a>] [<a href="https://doi.org/10.1002/ajmg.1320280421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3688033">Dodinval and Le Marec (1987)</a> reported 2 families, each with 2 cases of achondroplasia. In 1 family, a girl and her great aunt were affected; in the other, male and female first cousins. Both germinal mosaicism and paternal age effect appear to have their basis in the way spermatogonia are replenished, a feature that distinguishes gametogenesis in the male from that in the female. As outlined by <a href="#13" class="mim-tip-reference" title="Clermont, Y. <strong>Renewal of spermatogonia in man.</strong> Am. J. Anat. 118: 509-524, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5917196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5917196</a>] [<a href="https://doi.org/10.1002/aja.1001180211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5917196">Clermont (1966)</a>, spermatogonia go through a few mitotic divisions before embarking on the meiotic divisions that lead to mature sperm. Some of the products of the mitotic divisions are returned to the 'cell bank' to replenish the supply of spermatogonia. Mutations occurring during DNA replication can, therefore, accumulate, providing a basis for paternal age effect and for germinal mosaicism. <a href="#42" class="mim-tip-reference" title="Hoo, J. J. <strong>Alternative explanations for recurrent achondroplasia in siblings with normal parents.</strong> Clin. Genet. 25: 553-554, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6733952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6733952</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1984.tb00501.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6733952">Hoo (1984)</a> suggested a small insertional translocation as a possible mechanism for recurrent achondroplasia in sibs with normal parents. In discussing 'male-driven evolution' and the evidence for a generally higher mutation rate in males than in females, <a href="#16" class="mim-tip-reference" title="Crow, J. F. <strong>Molecular evolution--who is in the driver's seat?</strong> Nature Genet. 17: 129-130, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326921</a>] [<a href="https://doi.org/10.1038/ng1097-129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9326921">Crow (1997)</a> stated that the number of cell divisions required to generate sperm cells in a 30-year-old man is estimated at 400; the number of cell divisions that generate an egg is 24, irrespective of age. If mutation rates are proportional to the cell divisions, the male-to-female ratio should equal 17. In fact, the data show a higher ratio, as if mutation rates increase at a higher rate than the number of replications would predict--not surprising if fidelity of transcription and efficiency of repair mechanisms diminish with age. Studies in male and female birds by <a href="#22" class="mim-tip-reference" title="Ellegren, H., Fridolfsson, A.-K. <strong>Male-driven evolution of DNA sequences in birds.</strong> Nature Genet. 17: 182-184, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326938</a>] [<a href="https://doi.org/10.1038/ng1097-182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9326938">Ellegren and Fridolfsson (1997)</a> appeared to support male-driven evolution of DNA sequences in birds. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9326938+6507475+3688033+6733952+9326921+5917196+4061493" 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 severe phenotype of the homozygote for the ACH gene and the possibility that hypochondroplasia represents an allelic disorder were discussed in connection with the discussion of clinical features of achondroplasia.</p><p><a href="#57" class="mim-tip-reference" title="Langer, L. O., Jr., Schaefer, G. B., Wadsworth, D. T. <strong>Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.</strong> Am. J. Med. Genet. 47: 772-781, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8267011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8267011</a>] [<a href="https://doi.org/10.1002/ajmg.1320470535" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8267011">Langer et al. (1993)</a> described a patient who was doubly heterozygous for achondroplasia and pseudoachondroplasia (<a href="/entry/177170">177170</a>). <a href="#116" class="mim-tip-reference" title="Woods, C. G., Rogers, J. G., Mayne, V. <strong>Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.</strong> J. Med. Genet. 31: 565-569, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7966194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7966194</a>] [<a href="https://doi.org/10.1136/jmg.31.7.565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7966194">Woods et al. (1994)</a> described a family in which the father had pseudoachondroplasia and the mother had achondroplasia, and 2 daughters were doubly affected and a son had achondroplasia only. At birth, the 2 daughters appeared to have achondroplasia. Later, the development of a fixed lumbar gibbus, unusual radiographic changes in the spine, increasing joint laxity of the hands, and characteristic gait and hand posture made the appearance of pseudoachondroplasia apparent. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7966194+8267011" 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="Flynn, M. A., Pauli, R. M. <strong>Double heterozygosity in bone growth disorders: four new observations and review.</strong> Am. J. Med. Genet. 121A: 193-208, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923858</a>] [<a href="https://doi.org/10.1002/ajmg.a.20143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923858">Flynn and Pauli (2003)</a> described a fourth case with radiologic findings virtually identical to those described by <a href="#57" class="mim-tip-reference" title="Langer, L. O., Jr., Schaefer, G. B., Wadsworth, D. T. <strong>Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.</strong> Am. J. Med. Genet. 47: 772-781, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8267011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8267011</a>] [<a href="https://doi.org/10.1002/ajmg.1320470535" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8267011">Langer et al. (1993)</a> and <a href="#116" class="mim-tip-reference" title="Woods, C. G., Rogers, J. G., Mayne, V. <strong>Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.</strong> J. Med. Genet. 31: 565-569, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7966194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7966194</a>] [<a href="https://doi.org/10.1136/jmg.31.7.565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7966194">Woods et al. (1994)</a>. They commented that the fact that all the probands were initially thought to have achondroplasia alone is not surprising, since pseudoachondroplastic features usually are not identifiable until after 2 years of age in affected individuals. The patient described by <a href="#57" class="mim-tip-reference" title="Langer, L. O., Jr., Schaefer, G. B., Wadsworth, D. T. <strong>Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.</strong> Am. J. Med. Genet. 47: 772-781, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8267011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8267011</a>] [<a href="https://doi.org/10.1002/ajmg.1320470535" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8267011">Langer et al. (1993)</a> developed lumbar spinal stenosis at age 7.5 years. Both sibs in the report of <a href="#116" class="mim-tip-reference" title="Woods, C. G., Rogers, J. G., Mayne, V. <strong>Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.</strong> J. Med. Genet. 31: 565-569, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7966194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7966194</a>] [<a href="https://doi.org/10.1136/jmg.31.7.565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7966194">Woods et al. (1994)</a> had sufficiently severe stenosis of the foramen magnum to cause high cervical myelopathy requiring decompression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7966194+12923858+8267011" 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="Flynn, M. A., Pauli, R. M. <strong>Double heterozygosity in bone growth disorders: four new observations and review.</strong> Am. J. Med. Genet. 121A: 193-208, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923858</a>] [<a href="https://doi.org/10.1002/ajmg.a.20143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12923858">Flynn and Pauli (2003)</a> described a family in which the proband, her mother, and her maternal grandfather were all double heterozygotes for achondroplasia and for osteogenesis imperfecta type I (<a href="/entry/166200">166200</a>). Radiographic and clinical examination demonstrated features of both conditions, with neither being more prominent than would be expected for an individual heterozygous for each disorder alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923858" 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>Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but had not been measured. <a href="#64" class="mim-tip-reference" title="Mettler, G., Fraser, F. C. <strong>Recurrence risk for sibs of children with 'sporadic' achondroplasia.</strong> Am. J. Med. Genet. 90: 250-251, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678665</a>]" pmid="10678665">Mettler and Fraser (2000)</a> collected data from 11 Canadian genetics centers and arrived at an estimate of 1 in 443, or 0.02%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678665" 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="#100" class="mim-tip-reference" title="Stoll, C., Feingold, J. <strong>Do parents and grandparents of patients with achondroplasia have a higher cancer risk?</strong> Am. J. Med. Genet. 130A: 165-168, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372518</a>] [<a href="https://doi.org/10.1002/ajmg.a.30273" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15372518">Stoll and Feingold (2004)</a> performed analyses to determine whether a connection between teratogenesis and carcinogenesis is indicated by a higher cancer risk in parents of children with congenital anomalies. In achondroplasia, the new mutations are of paternal origin, raising the hypothesis of the existence of a 'mutator' gene acting in male meiosis and in somatic, mitotic cells in both sexes, which may favor the occurrence of cancer. By a questionnaire survey involving 76 males and 72 females with achondroplasia, <a href="#100" class="mim-tip-reference" title="Stoll, C., Feingold, J. <strong>Do parents and grandparents of patients with achondroplasia have a higher cancer risk?</strong> Am. J. Med. Genet. 130A: 165-168, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372518</a>] [<a href="https://doi.org/10.1002/ajmg.a.30273" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15372518">Stoll and Feingold (2004)</a> found that paternal grandfathers and grandmothers had significantly more cancers (56) than maternal grandfathers and grandmothers (24) (chi square = 14.80, p less than 0.001). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15372518" 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>In 3 sibs who were the product of the first and third pregnancies of healthy nonconsanguineous parents, <a href="#68" class="mim-tip-reference" title="Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F. <strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong> Am. J. Med. Genet. 146A: 784-786, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18266238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18266238</a>] [<a href="https://doi.org/10.1002/ajmg.a.32228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18266238">Natacci et al. (2008)</a> identified heterozygosity for the G380R mutation in the FGFR3 gene (<a href="/entry/134934#0001">134934.0001</a>). The mutation was not found in lymphocytic DNA from the parents; however, DNA analysis of a sperm sample from the 37-year-old father showed the G380R mutation. The authors stated that this was the second reported case of germinal mosaicism causing recurrent achondroplasia in a subsequent conception. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18266238" 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="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By linkage studies using DNA markers, <a href="#108" class="mim-tip-reference" title="Velinov, M., Slaugenhaupt, S. A., Stoilov, I., Scott, C. I., Jr., Gusella, J. F., Tsipouras, P. <strong>The gene for achondroplasia maps to the telomeric region of chromosome 4p.</strong> Nature Genet. 6: 314-317, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012397</a>] [<a href="https://doi.org/10.1038/ng0394-314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012397">Velinov et al. (1994)</a> and <a href="#58" class="mim-tip-reference" title="Le Merrer, M., Rousseau, F., Legeai-Mallet, L., Landais, J.-C., Pelet, A., Bonaventure, J., Sanak, M., Weissenbach, J., Stoll, C., Munnich, A., Maroteaux, P. <strong>A gene for achondroplasia--hypochondroplasia maps to chromosome 4p.</strong> Nature Genet. 6: 318-321, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012398</a>] [<a href="https://doi.org/10.1038/ng0394-318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012398">Le Merrer et al. (1994)</a> mapped the gene for achondroplasia and hypochondroplasia to the distal area of the short arm of chromosome 4 (4p16.3). <a href="#27" class="mim-tip-reference" title="Francomano, C. A., Ortiz de Luna, R. I., Hefferon, T. W., Bellus, G. A., Turner, C. E., Taylor, E., Meyers, D. A., Blanton, S. H., Murray, J. C., McIntosh, I., Hecht, J. T. <strong>Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p.</strong> Hum. Molec. Genet. 3: 787-792, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081365</a>] [<a href="https://doi.org/10.1093/hmg/3.5.787" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8081365">Francomano et al. (1994)</a> likewise mapped the ACH gene to 4p16.3, using 18 multigenerational families with achondroplasia and 8 anonymous dinucleotide repeat polymorphic markers from this region. No evidence of genetic heterogeneity was found. Analysis of a recombinant family localized the ACH locus to the 2.5-Mb region between D4S43 and the telomere. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8012398+8081365+8012397" 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>Exclusion Studies</em></strong></p><p>
|
|
<a href="#28" class="mim-tip-reference" title="Francomano, C. A., Pyeritz, R. E. <strong>Achondroplasia is not caused by mutation in the gene for type II collagen.</strong> Am. J. Med. Genet. 29: 955-961, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2899976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2899976</a>] [<a href="https://doi.org/10.1002/ajmg.1320290433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2899976">Francomano and Pyeritz (1988)</a> excluded COL2A1 as the site of the mutation in achondroplasia by use of probes spanning the gene in an analysis of genomic DNA from 49 affected persons and 2 multiplex families. No gross rearrangements were seen on Southern blot analysis, and linkage studies in the multiplex families demonstrated discordant inheritance of achondroplasia and COL2A1 alleles. Evidence against linkage to COL2A1 has been presented before by <a href="#72" class="mim-tip-reference" title="Ogilvie, D., Wordsworth, P., Thompson, E., Sykes, B. <strong>Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia.</strong> J. Med. Genet. 23: 19-22, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3005580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3005580</a>] [<a href="https://doi.org/10.1136/jmg.23.1.19" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3005580">Ogilvie et al. (1986)</a>. From their studies, <a href="#24" class="mim-tip-reference" title="Finkelstein, J. E., Doege, K., Yamada, Y., Pyeritz, R. E., Graham, J. M., Jr., Moeschler, J. B., Pauli, R. M., Hecht, J. T., Francomano, C. A. <strong>Analysis of the chondroitin sulfate proteoglycan core protein (CSPGP) gene in achondroplasia and pseudoachondroplasia.</strong> Am. J. Hum. Genet. 48: 97-102, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670752</a>]" pmid="1670752">Finkelstein et al. (1991)</a> concluded that mutations at the chondroitin sulfate proteoglycan core protein (CSPGP) locus do not cause achondroplasia or pseudoachondroplasia (<a href="/entry/177170">177170</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2899976+3005580+1670752" 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="#20" class="mim-tip-reference" title="Edwards, J. H., Huson, S., Ponder, B. <strong>Neurofibromatosis. (Letter)</strong> Lancet 332: 330 only, 1988. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2899736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2899736</a>] [<a href="https://doi.org/10.1016/s0140-6736(88)92377-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2899736">Edwards et al. (1988)</a> commented on a report, made at the national meeting of the Neurofibromatosis Foundation, of 2 individuals with achondroplasia and neurofibromatosis (<a href="/entry/162200">162200</a>) who had translocations involving the long arm of chromosome 17. In both cases the breakpoint was at the region consistent with localization of the neurofibromatosis gene by linkage studies; a third case of coincident achondroplasia and neurofibromatosis was also mentioned. <a href="#52" class="mim-tip-reference" title="Korenberg, J. R., Barker, D., Fain, P., Graham, J., Pribyl, T., Pulst, S.-M. <strong>Achondroplasia is not tightly linked to the locus for neurofibromatosis 1. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1025, 1989."None>Korenberg et al. (1989)</a> and <a href="#84" class="mim-tip-reference" title="Pulst, S.-M., Graham, J. M., Jr., Fain, P., Barker, D., Pribyl, T., Korenberg, J. R. <strong>The achondroplasia gene is not linked to the locus for neurofibromatosis 1 on chromosome 17.</strong> Hum. Genet. 85: 12-14, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162805</a>] [<a href="https://doi.org/10.1007/BF00276318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2162805">Pulst et al. (1990)</a> demonstrated by linkage analysis that the achondroplasia locus does not map between the 2 groups of markers flanking the gene for neurofibromatosis-1 on human chromosome 17. <a href="#109" class="mim-tip-reference" title="Verloes, A., Massart, B., Jossa, V., Langhendries, J. P., Hainaut, H., Paquot, J. P., Koulischer, L. <strong>Neuroblastoma in a dwarfed newborn: possible clue to the chromosomal localization of the gene for achondroplasia?</strong> Ann. Genet. 34: 25-26, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1952787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1952787</a>]" pmid="1952787">Verloes et al. (1991)</a> observed connatal neuroblastoma in an infant with achondroplasia and suggested that the achondroplasia gene may be located on the short arm of chromosome 1 where a neuroblastoma locus (see <a href="/entry/256700">256700</a>) appears to be situated. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1952787+2162805+2899736" 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">▼</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>Once the gene for achondroplasia was assigned to 4p16.3 by linkage analysis (<a href="#58" class="mim-tip-reference" title="Le Merrer, M., Rousseau, F., Legeai-Mallet, L., Landais, J.-C., Pelet, A., Bonaventure, J., Sanak, M., Weissenbach, J., Stoll, C., Munnich, A., Maroteaux, P. <strong>A gene for achondroplasia--hypochondroplasia maps to chromosome 4p.</strong> Nature Genet. 6: 318-321, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012398</a>] [<a href="https://doi.org/10.1038/ng0394-318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012398">Le Merrer et al., 1994</a>; <a href="#108" class="mim-tip-reference" title="Velinov, M., Slaugenhaupt, S. A., Stoilov, I., Scott, C. I., Jr., Gusella, J. F., Tsipouras, P. <strong>The gene for achondroplasia maps to the telomeric region of chromosome 4p.</strong> Nature Genet. 6: 314-317, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012397</a>] [<a href="https://doi.org/10.1038/ng0394-314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012397">Velinov et al., 1994</a>; <a href="#27" class="mim-tip-reference" title="Francomano, C. A., Ortiz de Luna, R. I., Hefferon, T. W., Bellus, G. A., Turner, C. E., Taylor, E., Meyers, D. A., Blanton, S. H., Murray, J. C., McIntosh, I., Hecht, J. T. <strong>Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p.</strong> Hum. Molec. Genet. 3: 787-792, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081365</a>] [<a href="https://doi.org/10.1093/hmg/3.5.787" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8081365">Francomano et al., 1994</a>), causative mutations were identified by the candidate gene approach and reported within 6 months of the first mapping report. Mutations in the gene for fibroblast growth factor receptor-3 (<a href="/entry/134934">134934</a>) were identified by <a href="#93" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al. (1994)</a> and independently by <a href="#90" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a>. The FGFR3 gene had previously been mapped to the same region, 4p16.3, as the ACH gene and the Huntington disease gene. The mutation in 15 of the 16 achondroplasia-affected chromosomes studied by <a href="#93" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al. (1994)</a> was the same, a G-to-A transition at nucleotide 1138 (<a href="/entry/134934#0001">134934.0001</a>) of the cDNA. The mutation on the only other ACH-affected chromosome 4 without the G-to-A transition at nucleotide 1138 had a G-to-C transversion at this same position (<a href="/entry/134934#0002">134934.0002</a>). Both mutations resulted in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3. The mutation was located in a CpG dinucleotide. <a href="#90" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a> found the G380R mutation in all cases studied: 17 sporadic cases and 6 unrelated familial cases. Because of the high mutation rate, it might have been predicted that the achondroplasia gene is large and that any one of many mutations could lead to the same or a similar (hypochondroplasia) phenotype. Such is apparently not the case. The fact that there are no reports of Wolf-Hirschhorn syndrome (<a href="/entry/194190">194190</a>) patients with stigmata of achondroplasia may indicate that the phenotype is due to some mechanism other than haploinsufficiency, e.g., represents a dominant-negative or gain-of-function effect. (The independent work of <a href="#93" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al. (1994)</a> and <a href="#90" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a> was reported in the 29 July issue of Cell and the 15 September issue of Nature, respectively.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8078586+8081365+8012398+7913883+8012397" 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="#7" class="mim-tip-reference" title="Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A. <strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong> Am. J. Hum. Genet. 56: 368-373, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847369</a>]" pmid="7847369">Bellus et al. (1995)</a> found that 150 of 154 unrelated achondroplasts had the G-to-A transition (<a href="/entry/134934#0001">134934.0001</a>) and 3 had the G-to-C transversion (<a href="/entry/134934#0002">134934.0002</a>) at nucleotide 1138 of the FGFR3 gene. All 153 had the gly380-to-arg substitution; in one individual, an atypical case, the gly380-to-arg substitution was missing. Nucleotide 1138 of the FGFR3 gene was the most mutable nucleotide in the human genome discovered at that time. <a href="#103" class="mim-tip-reference" title="Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B. <strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong> Europ. J. Pediat. 154: 215-219, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7758520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7758520</a>] [<a href="https://doi.org/10.1007/BF01954274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7758520">Superti-Furga et al. (1995)</a> reported the case of a newborn with achondroplasia who did not carry the mutation at nucleotide 1138 changing glycine-380 to arginine but had a mutation causing substitution of a nearby glycine with a cysteine (<a href="/entry/134934#0003">134934.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7847369+7758520" 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 FGFR3 gene was isolated and studied in connection with a search for the Huntington disease gene. The distribution of FGFR3 mRNA in embryonic mouse tissues was found to be more restricted than that of FGFR1 (<a href="/entry/136350">136350</a>) and FGFR2 (<a href="/entry/176943">176943</a>) mRNA. Outside of the developing central nervous system, the highest level of FGFR3 mRNA was found to be in the prebone cartilage rudiments of all bones, and during endochondral ossification, FGFR3 was detected in resting but not hypertrophic cartilage (<a href="#81" class="mim-tip-reference" title="Peters, K., Ornitz, D., Werner, S., Williams, L. <strong>Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis.</strong> Dev. Biol. 155: 423-430, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432397</a>] [<a href="https://doi.org/10.1006/dbio.1993.1040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432397">Peters et al., 1993</a>). The glycine-to-arginine substitution would have a major effect on the structure, function, or both of the hydrophobic transmembrane domain and most likely would have a significant effect on the function of the receptor. Five of 6 ACH homozygotes were homozygous for the G-to-A transition and each of 6 sporadic cases, including the parents of 2 of the homozygotes, were heterozygous for the 1138A allele and the wildtype allele. The fact that FGFR3 transcripts are present in fetal and adult brain (which has the highest levels of any tissue) may have relevance in connection with the megalencephaly which is thought to occur in achondroplasia (<a href="#17" class="mim-tip-reference" title="Dennis, J. P., Rosenberg, H. S., Alvord, E. C., Jr. <strong>Megalencephaly, internal hydrocephalus and other neurological aspects of achondroplasia.</strong> Brain 84: 427-445, 1961.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13885465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13885465</a>] [<a href="https://doi.org/10.1093/brain/84.3.427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13885465">Dennis et al., 1961</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13885465+8432397" 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>FGFR3 codes for at least 2 isoforms of the gene product by alternate use of 2 different exons that encode the last half of the third immunoglobulin domain (IgIII), which is primarily responsible for the ligand-binding specificity. The isoforms are preferentially activated by the various fibroblast growth factors.</p><p><a href="#91" class="mim-tip-reference" title="Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J. <strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong> Am. J. Med. Genet. 140A: 284-290, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411219</a>] [<a href="https://doi.org/10.1002/ajmg.a.31084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16411219">Rump et al. (2006)</a> reported a Dutch infant with a severe form of achondroplasia caused by 2 de novo mutations in the FGFR3 gene on the same allele: the common G380R mutation (<a href="/entry/134934#0001">134934.0001</a>) and L377R (<a href="/entry/134934#0027">134934.0027</a>). Allele-specific PCR analysis confirmed that the 2 mutations were in cis. From birth, the child had severe respiratory difficulties with multiple hypoxic episodes due to a combination of upper airway obstruction, pulmonary hypoplasia, and cervicomedullary compression. He eventually became ventilator dependent and died at age 4 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411219" 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="Horton, W. A. <strong>Recent milestones in achondroplasia research.</strong> Am. J. Med. Genet. 140A: 166-169, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16353253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16353253</a>] [<a href="https://doi.org/10.1002/ajmg.a.31029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16353253">Horton (2006)</a> reviewed work on the nature of the basic defect in achondroplasia. After mutations in FGFR3 were identified as the basis of achondroplasia in 1994, attention turned to how the mutation disturbed linear bone growth. Biochemical studies of the FGFR3 receptor combined with knockout experiments in mice revealed that FGFR3 is a negative regulator of chondrocyte proliferation and differentiation in the growth plate and that the mutations in achondroplasia and related disorders activate the receptor. Thus they can be viewed as gain-of-function mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16353253" 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="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> screened 18 exons of the FGFR3 gene in 25 patients with hypochondroplasia and 1 with achondroplasia in whom the common mutations G380R and N540K had been excluded. The authors identified 7 novel missense mutations, including 1 in the patient with achondroplasia (S279C; <a href="/entry/134934#0030">134934.0030</a>). <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> noted that 4 of the 6 extracellular mutations created additional cysteine residues and were associated with severe phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The diagnosis is based on the typical clinical and radiologic features; the delineation from severe hypochondroplasia may be arbitrary.</p><p>The demonstration of a very limited number of mutations causing achondroplasia and the ease with which they can be detected (1 PCR and 1 restriction digest) provides a simple method for prenatal diagnosis of ACH homozygotes in families at risk and in which the parents are heterozygous for either the 1138A or 1138C allele (<a href="#93" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al., 1994</a>). <a href="#93" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al. (1994)</a> expressed the opinion that other than the screening of at-risk pregnancies for homozygous ACH fetuses, any 'other application of the diagnostic test for ACH mutations should be prohibited.' <a href="#6" class="mim-tip-reference" title="Bellus, G. A., Escallon, C. S., de Luna, R. O., Shumway, J. B., Blakemore, K. J., McIntosh, I., Francomano, C. A. <strong>First-trimester prenatal diagnosis in couple at risk for homozygous achondroplasia. (Letter)</strong> Lancet 344: 1511-1512, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7968151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7968151</a>] [<a href="https://doi.org/10.1016/s0140-6736(94)90332-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7968151">Bellus et al. (1994)</a> practiced prenatal diagnosis by chorionic villus sampling at 10 weeks and 4 days of gestation, both parents having achondroplasia. Both parents and the fetus were shown to be heterozygous for the more common G-to-A transition. Homozygous achondroplasia was excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7913883+7968151" 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">▼</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>Recommendations for follow-up and management were reviewed at the first international symposium on achondroplasia (<a href="#70" class="mim-tip-reference" title="Nicoletti, B., Kopits, S. E., Ascani, E., McKusick, V. A. <strong>Human Achondroplasia: A Multidisciplinary Approach.</strong> New York: Plenum Press (pub.) 1988. Pp. 3-9."None>Nicoletti et al., 1988</a>) and by <a href="#45" class="mim-tip-reference" title="Horton, W. A., Hecht, J. T. <strong>The chondrodysplasias. In: Royce, P. M.; Steinmann, B. (eds.): Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects.</strong> New York: Wiley-Liss (pub.) 1993. Pp. 641-675."None>Horton and Hecht (1993)</a>. The recommendations included: measurements of growth and head circumference using growth curves standardized for achondroplasia (<a href="#47" class="mim-tip-reference" title="Horton, W. A., Rotter, J. I., Rimoin, D. L., Scott, C. L., Hall, J. G. <strong>Standard growth curves for achondroplasia.</strong> J. Pediat. 93: 435-438, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/690757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">690757</a>] [<a href="https://doi.org/10.1016/s0022-3476(78)81152-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="690757">Horton et al., 1978</a>); careful neurologic examinations (including CT, MRI, somatosensory evoked potentials and polysomnography) and surgical enlargement of the foramen magnum in cases of severe stenosis; management of frequent middle ear infections and dental crowding; measures to control obesity starting in early childhood; growth hormone therapy (<a href="#44" class="mim-tip-reference" title="Horton, W. A., Hecht, J. T., Hood, O. J., Marshall, R. N., Moore, W. V., Hollowell, J. G. <strong>Growth hormone therapy in achondroplasia.</strong> Am. J. Med. Genet. 42: 667-670, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1632435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1632435</a>] [<a href="https://doi.org/10.1002/ajmg.1320420508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1632435">Horton et al., 1992</a>), which is still experimental, and lengthening of the limb bones; tibial osteotomy or epiphysiodesis of the fibular growth plate to correct bowing of the legs; lumbar laminectomy for spinal stenosis which typically manifests in early adulthood; delivery of pregnant women with achondroplasia by cesarean section; and prenatal detection of affected fetuses by ultrasound. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1632435+690757" 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="Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I. <strong>Standard weight for height curves in achondroplasia.</strong> Am. J. Med. Genet. 62: 255-261, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882783</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882783">Hunter et al. (1996)</a> recommended that achondroplastic children stay within 1 SD of the mean weight for height curves for achondroplasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8882783" 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="Hoover-Fong, J. E., McGready, J., Schulze, K. J., Barnes, H., Scott, C. I. <strong>Weight for age charts for children with achondroplasia.</strong> Am. J. Med. Genet. 143A: 2227-2235, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17764078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17764078</a>] [<a href="https://doi.org/10.1002/ajmg.a.31873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17764078">Hoover-Fong et al. (2007)</a> developed weight for age, gender-specific growth curves for children with achondroplasia from birth through 16 years. The charts were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. The investigators proposed that the charts could be used in conjunction with current height for age charts developed by <a href="#47" class="mim-tip-reference" title="Horton, W. A., Rotter, J. I., Rimoin, D. L., Scott, C. L., Hall, J. G. <strong>Standard growth curves for achondroplasia.</strong> J. Pediat. 93: 435-438, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/690757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">690757</a>] [<a href="https://doi.org/10.1016/s0022-3476(78)81152-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="690757">Horton et al. (1978)</a> and weight for height charts developed by <a href="#51" class="mim-tip-reference" title="Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I. <strong>Standard weight for height curves in achondroplasia.</strong> Am. J. Med. Genet. 62: 255-261, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882783</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8882783">Hunter et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8882783+17764078+690757" 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="#94" class="mim-tip-reference" title="Shohat, M., Tick, D., Barakat, S., Bu, X., Melmed, S., Rimoin, D. L. <strong>Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia.</strong> J. Clin. Endocr. Metab. 81: 4033-4037, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923856</a>] [<a href="https://doi.org/10.1210/jcem.81.11.8923856" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8923856">Shohat et al. (1996)</a> investigated the effect of recombinant human growth hormone (hGH) treatment on the growth rate and proportion of individuals with achondroplasia and hypochondroplasia. They studied 15 individuals over 24 months including 6 months of observation, 12 months of hGH therapy (0.04 mg/kg/day), and 6 months of post treatment growth rate determination. The mean growth rate during hGH treatment (5.3 +/- 1.6 cm) of achondroplasts was significantly increased compared to pretreatment (4.0 +/- 1.0 cm/year, P less than 0.01) and posttreatment periods (3.1 +/- 1.3 cm; P less than 0.001). In the 4 children with hypochondroplasia, the growth rate during hGH treatment was 7.0 +/- 2.4 cm/year and 4.9 +/- 1.5 cm/year during the pre- and posttreatment periods, respectively. In achondroplasts, there was a significant increase in growth rate of only the lower segment (from 1.1 +/- 1.6 cm/year to 3.1 +/- 1.2 cm/year, P less than 0.02). Unexpectedly, this treatment does not seem to have a lesser effect on limbs than on trunk growth rate and, therefore, during 1 year of treatment, does not increase body disproportion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923856" 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="#113" class="mim-tip-reference" title="Waters, K. A., Everett, F., Sillence, D. O., Fagan, E. R., Sullivan, C. E. <strong>Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials.</strong> Am. J. Med. Genet. 59: 460-466, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8585566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8585566</a>] [<a href="https://doi.org/10.1002/ajmg.1320590412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8585566">Waters et al. (1995)</a> studied the results of treatment of obstructive sleep apnea in achondroplasia. Treatment included adenotonsillectomy, weight loss, and nasal-mask continuous positive airway pressure (CPAP). They observed improvements in measurements of disturbed sleep architecture and some evidence of improvement in neurologic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8585566" 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="#114" class="mim-tip-reference" title="Weber, G., Prinster, C., Meneghel, M., Russo, F., Mora, S., Puzzovio, M., Del Maschio, M., Chiumello, G. <strong>Human growth hormone treatment in prepubertal children with achondroplasia.</strong> Am. J. Med. Genet. 61: 396-400, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8834055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8834055</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960202)61:4<396::AID-AJMG17>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8834055">Weber et al. (1996)</a> studied the effects of recombinant human growth hormone treatment in 6 prepubertal children with achondroplasia, ranging in age from 2 to 8 years. They were given a GH dose of 0.1 IU/kg/day subcutaneously. During the year of treatment the growth velocity increased from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from the slight advancement of bone age in 2 patients. Their findings confirmed the individual variability in the response to GH treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8834055" 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="Horton, W. A. <strong>Recent milestones in achondroplasia research.</strong> Am. J. Med. Genet. 140A: 166-169, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16353253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16353253</a>] [<a href="https://doi.org/10.1002/ajmg.a.31029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16353253">Horton (2006)</a> reviewed milestones in achondroplasia research. As the molecular pathogenesis of achondroplasia emerged, interest shifted to therapy intended to counter the effects of the overactive receptor. One strategy involved chemical inhibitors selected for the FGFR3 tyrosine kinase. A second relied on blocking antibodies to interfere with binding of FGF ligands to FGFR3 (<a href="#3" class="mim-tip-reference" title="Aviezer, D., Golembo, M., Yayon, A. <strong>Fibroblast growth factor receptor-3 as a therapeutic target for achondroplasia--genetic short limbed dwarfism.</strong> Curr. Drug Targets 4: 353-365, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12816345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12816345</a>] [<a href="https://doi.org/10.2174/1389450033490993" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12816345">Aviezer et al., 2003</a>). A third possibility involved C-type natriuretic peptide (CNP; <a href="/entry/600296">600296</a>) which had been shown by <a href="#119" class="mim-tip-reference" title="Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K. <strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong> Nature Med. 10: 80-86, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14702637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14702637</a>] [<a href="https://doi.org/10.1038/nm971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14702637">Yasoda et al. (2004)</a> to downregulate FGF-induced activation of MAP kinase signaling pathways in growth plate chondrocytes and to counteract the effects of the achondroplasia mutation in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12816345+14702637+16353253" 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>In achondroplasia and thanatophoric dysplasia (<a href="/entry/187600">187600</a>), spinal canal and foramen magnum stenosis can cause serious neurologic complications. <a href="#62" class="mim-tip-reference" title="Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S. <strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong> Hum. Molec. Genet. 18: 227-240, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18923003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18923003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18923003[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18923003">Matsushita et al. (2009)</a> observed premature synchondrosis closure in the spine and cranial base in human cases of homozygous achondroplasia and thanatophoric dysplasia as well as in mouse models of achondroplasia. In both species, premature synchondrosis closure was associated with increased bone formation. Chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increased bone morphogenetic protein (Bmp) ligand (e.g., BMP7, <a href="/entry/112267">112267</a>) mRNA expression and decreased Bmp antagonist (e.g., noggin, <a href="/entry/602991">602991</a>) mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. The authors proposed that spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18923003" 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>C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). <a href="#59" class="mim-tip-reference" title="Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L. <strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong> Am. J. Hum. Genet. 91: 1108-1114, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23200862">Lorget et al. (2012)</a> reported the pharmacologic activity of a 39-amino acid CNP analog (BMN 111) with an extended plasma half-life due to its resistance to neutral endopeptidase (NEP; <a href="/entry/120520">120520</a>) digestion. In achondroplasia human growth plate chondrocytes, <a href="#59" class="mim-tip-reference" title="Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L. <strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong> Am. J. Hum. Genet. 91: 1108-1114, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23200862">Lorget et al. (2012)</a> demonstrated a decrease in the phosphorylation of extracellular signal-regulated kinases 1 (ERK1; <a href="/entry/601795">601795</a>) and 2 (ERK2; <a href="/entry/176948">176948</a>), confirming that this CNP analog inhibits FGF-mediated MAP kinase activation. Concomitantly, <a href="#59" class="mim-tip-reference" title="Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L. <strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong> Am. J. Hum. Genet. 91: 1108-1114, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23200862">Lorget et al. (2012)</a> analyzed the phenotype of Fgfr3(Y367C/+) mice and showed the presence of achondroplasia-related clinical features in this mouse model. <a href="#59" class="mim-tip-reference" title="Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L. <strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong> Am. J. Hum. Genet. 91: 1108-1114, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23200862">Lorget et al. (2012)</a> found that in Fgfr(Y367C) heterozygous mice, treatment with the CNP analog led to a significant recovery of bone growth. They also observed an increase in the axial and appendicular skeleton lengths and improvements in dwarfism-related clinical features including flattening of the skull, reduced crossbite, straightening of the tibias and femurs, and correction of the growth plate defect. <a href="#59" class="mim-tip-reference" title="Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L. <strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong> Am. J. Hum. Genet. 91: 1108-1114, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2012.10.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23200862">Lorget et al. (2012)</a> concluded that their results provided the proof of concept that BMN 111, a NEP-resistant CNP analog, might benefit individuals with achondroplasia and hypochondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23200862" 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="#92" class="mim-tip-reference" title="Savarirayan, R., Irving, M., Bacino, C. A., Bostwick, B., Charrow, J., Cormier-Daire, V., Sang, K.-H. L. Q., Dickson, P., Harmatz, P., Phillips, J., Owen, N., Cherukuri, A., Jayaram, K., Jeha, G. S., Larimore, K., Chan, M.-L., Labed, A. H., Day, J., Hoover-Fong, J. <strong>C-type natriuretic peptide analogue therapy in children with achondroplasia.</strong> New Eng. J. Med. 381: 25-35, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31269546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31269546</a>] [<a href="https://doi.org/10.1056/NEJMoa1813446" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31269546">Savarirayan et al. (2019)</a> reported the results of a phase 2 dose-finding and extension study of vosoritide (a biologic analog of C-type natriuretic peptide) given by once-daily subcutaneous injection in 35 children with achondroplasia aged 5 through 14 years. All patients had adverse events (most commonly injection-site reactions), and serious adverse events occurred in 4 of the 35 patients. Therapy was discontinued in 6 patients, in 1 due to an adverse event. During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed up to a dose of 15 mcg/kg, and a sustained increase was observed at doses of 15 and 30 mcg/kg for up to 42 months. There was no difference in efficacy or safety between the 15 and 30 mcg/kg doses, which supported the choice of the lower dose for further evaluations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31269546" 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="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Early estimates on the prevalence of achondroplasia are undoubtedly incorrect because of misdiagnosis. For example, <a href="#111" class="mim-tip-reference" title="Wallace, D. C., Exton, L. A., Pritchard, D. A., Leung, Y., Cooke, R. A. <strong>Severe achondroplasia: demonstration of probable heterogeneity within this clinical syndrome.</strong> J. Med. Genet. 7: 22-26, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5480962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5480962</a>] [<a href="https://doi.org/10.1136/jmg.7.1.22" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5480962">Wallace et al. (1970)</a> reported 2 female sibs as examples of achondroplasia; both died in the neonatal period and showed, in addition to chondrodystrophy, central harelip, hypoplastic lungs, and hydrocephalus. Without radiographic studies it is impossible to identify the nature of this condition, but it is certainly not true achondroplasia; Jeune asphyxiating thoracic dystrophy (<a href="/entry/208500">208500</a>), thanatophoric dwarfism (<a href="/entry/187600">187600</a>), and achondrogenesis are each possibilities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5480962" 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>Using modern diagnostic criteria, <a href="#31" class="mim-tip-reference" title="Gardner, R. J. M. <strong>A new estimate of the achondroplasia mutation rate.</strong> Clin. Genet. 11: 31-38, 1977.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/830446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">830446</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1977.tb01274.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="830446">Gardner (1977)</a> estimated the mutation rate at 0.000014. <a href="#74" class="mim-tip-reference" title="Orioli, I. M., Castilla, E. E., Barbosa-Neto, J. G. <strong>The birth prevalence rates for the skeletal dysplasias.</strong> J. Med. Genet. 23: 328-332, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3746832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3746832</a>] [<a href="https://doi.org/10.1136/jmg.23.4.328" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3746832">Orioli et al. (1986)</a> reported on the frequency of skeletal dysplasias among 349,470 births (live and stillbirths). The prevalence rate for achondroplasia was between 0.5 and 1.5/10,000 births. The mutation rate was estimated to be between 1.72 and 5.57 x 10(-5) per gamete per generation. The stated range is a consequence of the uncertainty of diagnosis in some cases. (The thanatophoric dysplasia/achondrogenesis group had a prevalence between 0.2 and 0.5/10,000 births. Osteogenesis imperfecta had a prevalence of 0.4/10,000 births. Only 1 case of diastrophic dysplasia was identified.) In the county of Fyn in Denmark, <a href="#1" class="mim-tip-reference" title="Andersen, P. E., Jr., Hauge, M. <strong>Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey.</strong> J. Med. Genet. 26: 37-44, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2783977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2783977</a>] [<a href="https://doi.org/10.1136/jmg.26.1.37" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2783977">Andersen and Hauge (1989)</a> determined the prevalence of generalized bone dysplasias by study of all children born in a 14-year period. The figures, which they referred to as 'point-prevalence at birth,' showed that achondroplasia was less common than generally thought (1.3 per 100,000), while osteogenesis imperfecta (21.8), multiple epiphyseal dysplasia tarda (9.0), achondrogenesis (6.4), osteopetrosis (5.1), and thanatophoric dysplasia (3.8) were found to be more frequent. <a href="#99" class="mim-tip-reference" title="Stoll, C., Dott, B., Roth, M.-P., Alembik, Y. <strong>Birth prevalence rates of skeletal dysplasias.</strong> Clin. Genet. 35: 88-92, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785882</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1989.tb02912.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2785882">Stoll et al. (1989)</a> found a mutation rate of 3.3 x 10(-5) per gamete per generation. In Spain, <a href="#61" class="mim-tip-reference" title="Martinez-Frias, M. L., Cereijo, A., Bermejo, E., Lopez, M., Sanchez, M., Gonzalo, C. <strong>Epidemiological aspects of mendelian syndromes in a Spanish population sample: I. Autosomal dominant malformation syndromes.</strong> Am. J. Med. Genet. 38: 622-625, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063907</a>] [<a href="https://doi.org/10.1002/ajmg.1320380424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2063907">Martinez-Frias et al. (1991)</a> found a frequency of achondroplasia of 2.53 per 100,000 live births. Total prevalence of autosomal dominant malformation syndromes was 12.1 per 100,000 live births. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3746832+2785882+2063907+830446+2783977" 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>Using data from 7 population-based birth defects monitoring programs in the United States, <a href="#112" class="mim-tip-reference" title="Waller, D. K., Correa, A., Vo, T. M., Wang, Y., Hobbs, C., Langlois, P. H., Pearson, K., Romitti, P. A., Shaw, G. M., Hecht, J. T. <strong>The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.</strong> Am. J. Med. Genet. 146A: 2385-2389, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18698630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18698630</a>] [<a href="https://doi.org/10.1002/ajmg.a.32485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18698630">Waller et al. (2008)</a> estimated the prevalence of achondroplasia and thanatophoric dysplasia and presented data on the association between older paternal age and these conditions. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 live births (1/27,780-1/16,670 live births). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 live births (1/33.330-1/47,620). The data suggested that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. In Texas, fathers that were 25-29, 30-34, 35-39, and over 40 years of age had significantly increased rates of de novo achondroplasia and thanatophoric dysplasia among their offspring compared with younger fathers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18698630" 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="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>It is of historic interest that <a href="#115" class="mim-tip-reference" title="Weinberg, W. <strong>Zur Vererbung des Zwergwuchses.</strong> Arch. Rass. Ges. Biol. 9: 710-717, 1912."None>Weinberg (1912)</a>, of Hardy-Weinberg law fame, noted in the data collected by Rischbieth and Barrington that sporadic cases were more often last-born than first-born. The studies by <a href="#65" class="mim-tip-reference" title="Morch, E. T. <strong>Chondrodystrophic dwarfs in Denmark.</strong> Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 3: 1-200, 1941."None>Morch (1941)</a> in Denmark and by <a href="#41" class="mim-tip-reference" title="Hobaek, A. <strong>Problems of Hereditary Chondrodysplasia.</strong> Oslo: Oslo Univ. Press (pub.) 1961."None>Hobaek (1961)</a> were early examples of full population studies.</p><p><a href="#53" class="mim-tip-reference" title="Kozma, C. <strong>Dwarfs in ancient Egypt.</strong> Am. J. Med. Genet. 140A: 303-311, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380966</a>] [<a href="https://doi.org/10.1002/ajmg.a.31068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380966">Kozma (2006)</a> described some of the earliest biologic evidence of dwarfism from ancient Egypt, dating as far back as 4500 BCE. Due to the hot, dry climate and natural and artificial mummification, Egypt is a major source of archeological information on achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380966" 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="Bernal, J. E., Briceno, I. <strong>Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.</strong> Clin. Genet. 70: 188-191, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922718</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16922718">Bernal and Briceno (2006)</a> examined pottery artifacts from the Tumaco-La Tolita culture, which existed on the border of present-day Colombia and Ecuador approximately 2,500 years ago, and described a figurine consisting of head, thorax, and arms, which showed a cranial deformation, prominent forehead, low nasal bridge, jaw prognathism, and short neck, characteristics suggestive of achondroplasia. <a href="#8" class="mim-tip-reference" title="Bernal, J. E., Briceno, I. <strong>Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.</strong> Clin. Genet. 70: 188-191, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922718</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00670.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16922718">Bernal and Briceno (2006)</a> believed these artifacts to be among the earliest artistic representations of disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922718" 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="#54" class="mim-tip-reference" title="Kozma, C. <strong>Skeletal dysplasia in ancient Egypt.</strong> Am. J. Med. Genet. 146A: 3104-3112, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19006207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19006207</a>] [<a href="https://doi.org/10.1002/ajmg.a.32501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19006207">Kozma (2008)</a> provided a detailed historical review of skeletal dysplasias, particularly achondroplasia, in ancient Egypt. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19006207" 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="#102" class="mim-tip-reference" title="Strom, C. M. <strong>Achondroplasia due to DNA insertion into the type II collagen gene. (Abstract)</strong> Pediat. Res. 18: 226A, 1984."None>Strom (1984)</a> and <a href="#23" class="mim-tip-reference" title="Eng, C. E. L., Pauli, R. M., Strom, C. M. <strong>Nonrandom association of a type II procollagen genotype with achondroplasia.</strong> Proc. Nat. Acad. Sci. 82: 5465-5469, 1985. Note: Retraction: Proc. Nat. Acad. Sci. 83:5354 only, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991928</a>] [<a href="https://doi.org/10.1073/pnas.82.16.5465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2991928">Eng et al. (1985)</a> purported to find abnormality of the type II collagen gene in achondroplasia. If such a defect is present, one might expect ocular abnormality in achondroplasia inasmuch as type II collagen is present in vitreous. SED congenita was a more plausible candidate for a structural defect of type II collagen because it is a dominant disorder that combines skeletal dysplasia with vitreous degeneration and deafness (experimental studies with antibodies to type II collagen indicate that this collagen type is represented in the middle ear); subsequently, defects were in fact found in the COL2A1 gene in SEDC. The report by <a href="#23" class="mim-tip-reference" title="Eng, C. E. L., Pauli, R. M., Strom, C. M. <strong>Nonrandom association of a type II procollagen genotype with achondroplasia.</strong> Proc. Nat. Acad. Sci. 82: 5465-5469, 1985. Note: Retraction: Proc. Nat. Acad. Sci. 83:5354 only, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991928</a>] [<a href="https://doi.org/10.1073/pnas.82.16.5465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2991928">Eng et al. (1985)</a> was withdrawn in 1986 because figures, 'which were generated in the laboratory of C. Strom and C. Eng, were improperly assembled and therefore cannot be used to support the conclusions of the article.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2991928" 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">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Beighton1981" class="mim-tip-reference" title="Beighton, P., Bathfield, C. A. <strong>Gibbal achondroplasia.</strong> J. Bone Joint Surg. Br. 63: 328-329, 1981.">Beighton and Bathfield (1981)</a>; <a href="#Cohen1967" class="mim-tip-reference" title="Cohen, M. E., Rosenthal, A. D., Matson, D. D. <strong>Neurological abnormalities in achondroplastic children.</strong> J. Pediat. 71: 367-376, 1967.">Cohen et al. (1967)</a>; <a href="#Durr1968" class="mim-tip-reference" title="Durr, D. K. <strong>Eine neue Dysostoseform mit Mikromelie bei zwei Geschwistern.</strong> Helv. Paediat. Acta 23: 184-194, 1968.">Durr (1968)</a>; <a href="#Elejalde1983" class="mim-tip-reference" title="Elejalde, B. R., Elejalde, M. M., Hamilton, P. R., Lombardi, J. N. <strong>Prenatal diagnosis in two pregnancies of an achondroplastic woman.</strong> Am. J. Med. Genet. 15: 437-439, 1983.">Elejalde et al. (1983)</a>; <a href="#Fremion1984" class="mim-tip-reference" title="Fremion, A. S., Garg, B. P., Kalsbeck, J. <strong>Apnea as the sole manifestation of cord compression in achondroplasia.</strong> J. Pediat. 104: 398-401, 1984.">Fremion et al. (1984)</a>; <a href="#Hall1979" class="mim-tip-reference" title="Hall, J. G., Golbus, M. S., Graham, C. B., Pagon, R. A., Luthy, D. A., Filly, R. A. <strong>Failure of early prenatal diagnosis in classic achondroplasia.</strong> Am. J. Med. Genet. 3: 371-375, 1979.">Hall et al. (1979)</a>; <a href="#Maroteaux1964" class="mim-tip-reference" title="Maroteaux, P., Lamy, P. <strong>Achondroplasia in man and animals.</strong> Clin. Orthop. 33: 91-103, 1964.">Maroteaux and Lamy (1964)</a>; <a href="#Morgan1980" class="mim-tip-reference" title="Morgan, D. F., Young, R. F. <strong>Spinal neurological complications of achondroplasia: results of surgical treatment.</strong> J. Neurosurg. 52: 463-472, 1980.">Morgan and Young (1980)</a>; <a href="#Murdoch1970" class="mim-tip-reference" title="Murdoch, J. L., Walker, B. A., Hall, J. G., Abbey, H., Smith, K. K., McKusick, V. A. <strong>Achondroplasia--a genetic and statistical survey.</strong> Ann. Hum. Genet. 33: 227-244, 1970.">Murdoch et al.
|
|
(1970)</a>; <a href="#Oberklaid1979" class="mim-tip-reference" title="Oberklaid, F., Danks, D. M., Jensen, F., Stace, L., Rosshandler, S. <strong>Achondroplasia and hyperchondroplasia: comments on frequency, mutation rate, and radiological features in skull and spine.</strong> J. Med. Genet. 16: 140-146, 1979.">Oberklaid et al. (1979)</a>; <a href="#Opitz1984" class="mim-tip-reference" title="Opitz, J. M. <strong>'Unstable premutation' in achondroplasia: penetrance vs phenotrance. (Editorial)</strong> Am. J. Med. Genet. 19: 251-254, 1984.">Opitz (1984)</a>; <a href="#Pauli1983" class="mim-tip-reference" title="Pauli, R. M., Conroy, M. M., Langer, L. O., Jr., McLone, D. G., Naidich, T., Franciosi, R., Ratner, I. M., Copps, S. C. <strong>Homozygous achondroplasia with survival beyond infancy.</strong> Am. J. Med. Genet. 16: 459-473, 1983.">Pauli et al. (1983)</a>; <a href="#Penrose1957" class="mim-tip-reference" title="Penrose, L. S. <strong>Parental age in achondroplasia and mongolism.</strong> Am. J. Hum. Genet. 9: 167-169, 1957.">Penrose (1957)</a>; <a href="#Pyeritz1987" class="mim-tip-reference" title="Pyeritz, R. E., Sack, G. H., Jr., Udvarhelyi, G. B. <strong>Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients.</strong> Am. J. Med. Genet. 28: 433-444, 1987.">Pyeritz et al. (1987)</a>; <a href="#Rimoin1970" class="mim-tip-reference" title="Rimoin, D. L., Hughes, G. N., Kaufman, R. L., Rosenthal, R. E., McAlister, W. H., Silberberg, R. <strong>Endochondral ossification in achondroplastic dwarfism.</strong> New Eng. J. Med. 283: 728-735, 1970.">Rimoin et al. (1970)</a>; <a href="#Siebens1978" class="mim-tip-reference" title="Siebens, A. A., Hungerford, D. S., Kirby, N. A. <strong>Curves of the achondroplastic spine: a new hypothesis.</strong> Johns Hopkins Med. J. 142: 205-210, 1978.">Siebens
|
|
et al. (1978)</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">▼</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="Andersen1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andersen, P. E., Jr., Hauge, M.
|
|
<strong>Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey.</strong>
|
|
J. Med. Genet. 26: 37-44, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2783977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2783977</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2783977" 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.26.1.37" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Aterman1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aterman, K., Welch, J. P., Taylor, P. G.
|
|
<strong>Presumed homozygous achondroplasia: a review and report of a further case.</strong>
|
|
Path. Res. Pract. 178: 27-39, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6359101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6359101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6359101" 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/S0344-0338(83)80082-X" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Aviezer2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aviezer, D., Golembo, M., Yayon, A.
|
|
<strong>Fibroblast growth factor receptor-3 as a therapeutic target for achondroplasia--genetic short limbed dwarfism.</strong>
|
|
Curr. Drug Targets 4: 353-365, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12816345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12816345</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12816345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2174/1389450033490993" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Beighton1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beighton, P., Bathfield, C. A.
|
|
<strong>Gibbal achondroplasia.</strong>
|
|
J. Bone Joint Surg. Br. 63: 328-329, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7263742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7263742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7263742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1302/0301-620X.63B3.7263742" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Beighton1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beighton, P., Sujansky, E., Patzak, B., Portele, K. A.
|
|
<strong>Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.</strong>
|
|
Am. J. Med. Genet. 47: 843-847, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8279481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8279481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8279481" 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.1320470609" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bellus1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Escallon, C. S., de Luna, R. O., Shumway, J. B., Blakemore, K. J., McIntosh, I., Francomano, C. A.
|
|
<strong>First-trimester prenatal diagnosis in couple at risk for homozygous achondroplasia. (Letter)</strong>
|
|
Lancet 344: 1511-1512, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7968151/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7968151</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7968151" 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(94)90332-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bellus1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A.
|
|
<strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong>
|
|
Am. J. Hum. Genet. 56: 368-373, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7847369" 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="Bernal2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernal, J. E., Briceno, I.
|
|
<strong>Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.</strong>
|
|
Clin. Genet. 70: 188-191, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922718" 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.1399-0004.2006.00670.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Boor1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boor, R., Fricke, G., Bruhl, K., Spranger, J.
|
|
<strong>Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia.</strong>
|
|
Europ. J. Pediat. 158: 662-667, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10445347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10445347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10445347" 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/s004310051172" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Bowen1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowen, P.
|
|
<strong>Achondroplasia in two sisters with normal parents.</strong>
|
|
Birth Defects Orig. Art. Ser. X(12): 31-36, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4461062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4461062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4461062" 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="11" class="mim-anchor"></a>
|
|
<a id="Chiari1913" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chiari, H.
|
|
<strong>Ueber familiaere Chondrodystrophia foetalis.</strong>
|
|
Muench. Med. Wschr. 60: 248-249, 1913.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Chitayat1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D.
|
|
<strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong>
|
|
Am. J. Med. Genet. 84: 401-405, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360393</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360393" 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="13" class="mim-anchor"></a>
|
|
<a id="Clermont1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clermont, Y.
|
|
<strong>Renewal of spermatogonia in man.</strong>
|
|
Am. J. Anat. 118: 509-524, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5917196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5917196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5917196" 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/aja.1001180211" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Cohen1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cohen, M. E., Rosenthal, A. D., Matson, D. D.
|
|
<strong>Neurological abnormalities in achondroplastic children.</strong>
|
|
J. Pediat. 71: 367-376, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5298504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5298504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5298504" 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/s0022-3476(67)80296-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Cohn1956" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cohn, S., Weinberg, A.
|
|
<strong>Identical hydrocephalic achondroplastic twins. Subsequent delivery of single sibling with same abnormality.</strong>
|
|
Am. J. Obstet. Gynec. 72: 1346-1348, 1956.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13372616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13372616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13372616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9378(56)90797-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Crow1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crow, J. F.
|
|
<strong>Molecular evolution--who is in the driver's seat?</strong>
|
|
Nature Genet. 17: 129-130, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326921" 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/ng1097-129" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Dennis1961" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dennis, J. P., Rosenberg, H. S., Alvord, E. C., Jr.
|
|
<strong>Megalencephaly, internal hydrocephalus and other neurological aspects of achondroplasia.</strong>
|
|
Brain 84: 427-445, 1961.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13885465/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13885465</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13885465" 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/brain/84.3.427" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Dodinval1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dodinval, P., Le Marec, B.
|
|
<strong>Genetic counselling in unexpected familial recurrence of achondroplasia.</strong>
|
|
Am. J. Med. Genet. 28: 949-954, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3688033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3688033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3688033" 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.1320280421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Durr1968" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Durr, D. K.
|
|
<strong>Eine neue Dysostoseform mit Mikromelie bei zwei Geschwistern.</strong>
|
|
Helv. Paediat. Acta 23: 184-194, 1968.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5699022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5699022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5699022" 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="20" class="mim-anchor"></a>
|
|
<a id="Edwards1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Edwards, J. H., Huson, S., Ponder, B.
|
|
<strong>Neurofibromatosis. (Letter)</strong>
|
|
Lancet 332: 330 only, 1988. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2899736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2899736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2899736" 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(88)92377-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Elejalde1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elejalde, B. R., Elejalde, M. M., Hamilton, P. R., Lombardi, J. N.
|
|
<strong>Prenatal diagnosis in two pregnancies of an achondroplastic woman.</strong>
|
|
Am. J. Med. Genet. 15: 437-439, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6881210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6881210</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6881210" 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.1320150308" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Ellegren1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellegren, H., Fridolfsson, A.-K.
|
|
<strong>Male-driven evolution of DNA sequences in birds.</strong>
|
|
Nature Genet. 17: 182-184, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326938</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326938" 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/ng1097-182" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Eng1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eng, C. E. L., Pauli, R. M., Strom, C. M.
|
|
<strong>Nonrandom association of a type II procollagen genotype with achondroplasia.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 5465-5469, 1985. Note: Retraction: Proc. Nat. Acad. Sci. 83:5354 only, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2991928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2991928</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2991928" 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.82.16.5465" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Finkelstein1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Finkelstein, J. E., Doege, K., Yamada, Y., Pyeritz, R. E., Graham, J. M., Jr., Moeschler, J. B., Pauli, R. M., Hecht, J. T., Francomano, C. A.
|
|
<strong>Analysis of the chondroitin sulfate proteoglycan core protein (CSPGP) gene in achondroplasia and pseudoachondroplasia.</strong>
|
|
Am. J. Hum. Genet. 48: 97-102, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1670752" 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="Fitzsimmons1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fitzsimmons, J. S.
|
|
<strong>Familial recurrence of achondroplasia.</strong>
|
|
Am. J. Med. Genet. 22: 609-613, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4061493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4061493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4061493" 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.1320220320" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Flynn2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Flynn, M. A., Pauli, R. M.
|
|
<strong>Double heterozygosity in bone growth disorders: four new observations and review.</strong>
|
|
Am. J. Med. Genet. 121A: 193-208, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12923858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12923858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12923858" 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.20143" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Francomano1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Ortiz de Luna, R. I., Hefferon, T. W., Bellus, G. A., Turner, C. E., Taylor, E., Meyers, D. A., Blanton, S. H., Murray, J. C., McIntosh, I., Hecht, J. T.
|
|
<strong>Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p.</strong>
|
|
Hum. Molec. Genet. 3: 787-792, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8081365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8081365</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8081365" 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/3.5.787" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Francomano1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Pyeritz, R. E.
|
|
<strong>Achondroplasia is not caused by mutation in the gene for type II collagen.</strong>
|
|
Am. J. Med. Genet. 29: 955-961, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2899976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2899976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2899976" 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.1320290433" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Fremion1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fremion, A. S., Garg, B. P., Kalsbeck, J.
|
|
<strong>Apnea as the sole manifestation of cord compression in achondroplasia.</strong>
|
|
J. Pediat. 104: 398-401, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6707795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6707795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6707795" 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/s0022-3476(84)81103-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Fryns1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fryns, J. P., Kleczkowska, A., Verresen, H., van den Berghe, H.
|
|
<strong>Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents.</strong>
|
|
Clin. Genet. 24: 156-158, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6627718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6627718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6627718" 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.1399-0004.1983.tb02232.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Gardner1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gardner, R. J. M.
|
|
<strong>A new estimate of the achondroplasia mutation rate.</strong>
|
|
Clin. Genet. 11: 31-38, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/830446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">830446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=830446" 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.1399-0004.1977.tb01274.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Hall1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Dorst, J. P., Taybi, H., Scott, C. I., Jr., Langer, L. O., Jr., McKusick, V. A.
|
|
<strong>Two probable cases of homozygosity for the achondroplasia gene.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 24-34, 1969.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Hall1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Golbus, M. S., Graham, C. B., Pagon, R. A., Luthy, D. A., Filly, R. A.
|
|
<strong>Failure of early prenatal diagnosis in classic achondroplasia.</strong>
|
|
Am. J. Med. Genet. 3: 371-375, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/474637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">474637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=474637" 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.1320030408" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Hall1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Horton, W., Kelly, T., Scott, C. I.
|
|
<strong>Head growth in achondroplasia: use of ultrasound studies. (Letter)</strong>
|
|
Am. J. Med. Genet. 13: 105, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7137217/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7137217</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7137217" 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.1320130116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Hall1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, J. G.
|
|
<strong>The natural history of achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 3-10.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Hecht1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Francomano, C. A., Horton, W. A., Annegers, J. F.
|
|
<strong>Mortality in achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 41: 454-464, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3631079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3631079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3631079" 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="37" class="mim-anchor"></a>
|
|
<a id="Hecht1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Hood, O. J., Schwartz, R. J., Hennessey, J. C., Bernhardt, B. A., Horton, W. A.
|
|
<strong>Obesity in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 31: 597-602, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3228140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3228140</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3228140" 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.1320310314" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Hecht1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Thompson, N. M., Weir, T., Patchell, L., Horton, W. A.
|
|
<strong>Cognitive and motor skills in achondroplastic infants: neurologic and respiratory correlates.</strong>
|
|
Am. J. Med. Genet. 41: 208-211, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1785636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1785636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1785636" 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.1320410215" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Henderson2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B.
|
|
<strong>Germline and somatic mosaicism in achondroplasia.</strong>
|
|
J. Med. Genet. 37: 956-958, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186939" 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.37.12.956" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Heuertz2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J.
|
|
<strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong>
|
|
Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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/sj.ejhg.5201700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Hobaek1961" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hobaek, A.
|
|
<strong>Problems of Hereditary Chondrodysplasia.</strong>
|
|
Oslo: Oslo Univ. Press (pub.) 1961.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Hoo1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoo, J. J.
|
|
<strong>Alternative explanations for recurrent achondroplasia in siblings with normal parents.</strong>
|
|
Clin. Genet. 25: 553-554, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6733952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6733952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6733952" 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.1399-0004.1984.tb00501.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Hoover-Fong2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoover-Fong, J. E., McGready, J., Schulze, K. J., Barnes, H., Scott, C. I.
|
|
<strong>Weight for age charts for children with achondroplasia.</strong>
|
|
Am. J. Med. Genet. 143A: 2227-2235, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17764078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17764078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17764078" 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.31873" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Horton1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hecht, J. T., Hood, O. J., Marshall, R. N., Moore, W. V., Hollowell, J. G.
|
|
<strong>Growth hormone therapy in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 42: 667-670, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1632435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1632435</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1632435" 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.1320420508" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Horton1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hecht, J. T.
|
|
<strong>The chondrodysplasias. In: Royce, P. M.; Steinmann, B. (eds.): Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects.</strong>
|
|
New York: Wiley-Liss (pub.) 1993. Pp. 641-675.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Horton1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hood, O. J., Machado, M. A., Campbell, D.
|
|
<strong>Growth plate cartilage studies in achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 81-89.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Horton1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Rotter, J. I., Rimoin, D. L., Scott, C. L., Hall, J. G.
|
|
<strong>Standard growth curves for achondroplasia.</strong>
|
|
J. Pediat. 93: 435-438, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/690757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">690757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=690757" 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/s0022-3476(78)81152-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Horton2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horton, W. A.
|
|
<strong>Recent milestones in achondroplasia research.</strong>
|
|
Am. J. Med. Genet. 140A: 166-169, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16353253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16353253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16353253" 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.31029" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Huggins1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T.
|
|
<strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong>
|
|
Am. J. Med. Genet. 84: 396-400, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360392" 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="50" class="mim-anchor"></a>
|
|
<a id="Hunter1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr.
|
|
<strong>Medical complications of achondroplasia: a multicentre patient review.</strong>
|
|
J. Med. Genet. 35: 705-712, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9733026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9733026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9733026" 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.35.9.705" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Hunter1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I.
|
|
<strong>Standard weight for height curves in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 62: 255-261, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8882783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8882783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8882783" 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/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Korenberg1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Korenberg, J. R., Barker, D., Fain, P., Graham, J., Pribyl, T., Pulst, S.-M.
|
|
<strong>Achondroplasia is not tightly linked to the locus for neurofibromatosis 1. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1025, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Kozma2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kozma, C.
|
|
<strong>Dwarfs in ancient Egypt.</strong>
|
|
Am. J. Med. Genet. 140A: 303-311, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380966</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380966" 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.31068" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Kozma2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kozma, C.
|
|
<strong>Skeletal dysplasia in ancient Egypt.</strong>
|
|
Am. J. Med. Genet. 146A: 3104-3112, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19006207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19006207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19006207" 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.32501" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Lachman1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lachman, R. S.
|
|
<strong>Neurologic abnormalities in the skeletal dysplasias: a clinical and radiological perspective.</strong>
|
|
Am. J. Med. Genet. 69: 33-43, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9066881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9066881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9066881" 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/(sici)1096-8628(19970303)69:1<33::aid-ajmg7>3.0.co;2-u" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Langer1967" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Langer, L. O., Jr., Baumann, P. A., Gorlin, R. J.
|
|
<strong>Achondroplasia.</strong>
|
|
Am. J. Roentgen. Radium Ther. Nucl. Med. 100: 12-26, 1967.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6023888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6023888</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6023888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2214/ajr.100.1.12" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Langer1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Langer, L. O., Jr., Schaefer, G. B., Wadsworth, D. T.
|
|
<strong>Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.</strong>
|
|
Am. J. Med. Genet. 47: 772-781, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8267011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8267011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8267011" 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.1320470535" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Le Merrer1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Le Merrer, M., Rousseau, F., Legeai-Mallet, L., Landais, J.-C., Pelet, A., Bonaventure, J., Sanak, M., Weissenbach, J., Stoll, C., Munnich, A., Maroteaux, P.
|
|
<strong>A gene for achondroplasia--hypochondroplasia maps to chromosome 4p.</strong>
|
|
Nature Genet. 6: 318-321, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012398</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8012398" 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/ng0394-318" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Lorget2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L.
|
|
<strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 91: 1108-1114, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23200862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23200862</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23200862[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=23200862" 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.2012.10.014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Maroteaux1964" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maroteaux, P., Lamy, P.
|
|
<strong>Achondroplasia in man and animals.</strong>
|
|
Clin. Orthop. 33: 91-103, 1964.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5889028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5889028</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5889028" 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="61" class="mim-anchor"></a>
|
|
<a id="Martinez-Frias1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martinez-Frias, M. L., Cereijo, A., Bermejo, E., Lopez, M., Sanchez, M., Gonzalo, C.
|
|
<strong>Epidemiological aspects of mendelian syndromes in a Spanish population sample: I. Autosomal dominant malformation syndromes.</strong>
|
|
Am. J. Med. Genet. 38: 622-625, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063907" 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.1320380424" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Matsushita2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S.
|
|
<strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong>
|
|
Hum. Molec. Genet. 18: 227-240, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18923003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18923003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18923003[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=18923003" 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/ddn339" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="McKusick1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kelly, T. E., Dorst, J. P.
|
|
<strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong>
|
|
J. Med. Genet. 10: 11-16, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4697848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4697848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4697848" 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.10.1.11" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Mettler2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mettler, G., Fraser, F. C.
|
|
<strong>Recurrence risk for sibs of children with 'sporadic' achondroplasia.</strong>
|
|
Am. J. Med. Genet. 90: 250-251, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678665" 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="65" class="mim-anchor"></a>
|
|
<a id="Morch1941" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morch, E. T.
|
|
<strong>Chondrodystrophic dwarfs in Denmark.</strong>
|
|
Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 3: 1-200, 1941.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Morgan1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morgan, D. F., Young, R. F.
|
|
<strong>Spinal neurological complications of achondroplasia: results of surgical treatment.</strong>
|
|
J. Neurosurg. 52: 463-472, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7373371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7373371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7373371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3171/jns.1980.52.4.0463" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Murdoch1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murdoch, J. L., Walker, B. A., Hall, J. G., Abbey, H., Smith, K. K., McKusick, V. A.
|
|
<strong>Achondroplasia--a genetic and statistical survey.</strong>
|
|
Ann. Hum. Genet. 33: 227-244, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5504223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5504223</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5504223" 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.1469-1809.1970.tb01648.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Natacci2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F.
|
|
<strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong>
|
|
Am. J. Med. Genet. 146A: 784-786, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18266238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18266238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18266238" 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.32228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Nelson1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nelson, F. W., Hecht, J. T., Horton, W. A., Butler, I. J., Goldie, W. D., Miner, M.
|
|
<strong>Neurological basis of respiratory complications in achondroplasia.</strong>
|
|
Ann. Neurol. 24: 89-93, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3415202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3415202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3415202" 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/ana.410240117" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Nicoletti1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nicoletti, B., Kopits, S. E., Ascani, E., McKusick, V. A.
|
|
<strong>Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 3-9.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Oberklaid1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oberklaid, F., Danks, D. M., Jensen, F., Stace, L., Rosshandler, S.
|
|
<strong>Achondroplasia and hyperchondroplasia: comments on frequency, mutation rate, and radiological features in skull and spine.</strong>
|
|
J. Med. Genet. 16: 140-146, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/458831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">458831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=458831" 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.16.2.140" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Ogilvie1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ogilvie, D., Wordsworth, P., Thompson, E., Sykes, B.
|
|
<strong>Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia.</strong>
|
|
J. Med. Genet. 23: 19-22, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3005580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3005580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3005580" 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.23.1.19" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Opitz1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Opitz, J. M.
|
|
<strong>'Unstable premutation' in achondroplasia: penetrance vs phenotrance. (Editorial)</strong>
|
|
Am. J. Med. Genet. 19: 251-254, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6507476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6507476</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6507476" 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.1320190207" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Orioli1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orioli, I. M., Castilla, E. E., Barbosa-Neto, J. G.
|
|
<strong>The birth prevalence rates for the skeletal dysplasias.</strong>
|
|
J. Med. Genet. 23: 328-332, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3746832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3746832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3746832" 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.23.4.328" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Pauli1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Conroy, M. M., Langer, L. O., Jr., McLone, D. G., Naidich, T., Franciosi, R., Ratner, I. M., Copps, S. C.
|
|
<strong>Homozygous achondroplasia with survival beyond infancy.</strong>
|
|
Am. J. Med. Genet. 16: 459-473, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6660245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6660245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6660245" 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.1320160404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Pauli1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Horton, V. K., Glinski, L. P., Reiser, C. A.
|
|
<strong>Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 56: 732-744, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7887429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7887429</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7887429" 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="Pauli1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Modaff, P.
|
|
<strong>Jugular bulb dehiscence in achondroplasia.</strong>
|
|
Int. J. Pediat. Otorhinolaryng. 48: 169-174, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10375043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10375043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10375043" 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/s0165-5876(99)00033-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Pauli1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Scott, C. I., Wassman, E. R., Jr., Gilbert, E. F., Leavitt, L. A., Ver Hoeve, J., Hall, J. G., Partington, M. W., Jones, K. L., Sommer, A., Feldman, W., Langer, L. O., Rimoin, D. L., Hecht, J. T., Lebovitz, R.
|
|
<strong>Apnea and sudden unexpected death in infants with achondroplasia.</strong>
|
|
J. Pediat. 104: 342-348, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6707788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6707788</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6707788" 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/s0022-3476(84)81092-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Penrose1955" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Penrose, L. S.
|
|
<strong>Parental age and mutation.</strong>
|
|
Lancet 266: 312-313, 1955. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13243724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13243724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13243724" 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(55)92305-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Penrose1957" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Penrose, L. S.
|
|
<strong>Parental age in achondroplasia and mongolism.</strong>
|
|
Am. J. Hum. Genet. 9: 167-169, 1957.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13507646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13507646</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13507646" 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="Peters1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peters, K., Ornitz, D., Werner, S., Williams, L.
|
|
<strong>Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis.</strong>
|
|
Dev. Biol. 155: 423-430, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432397" 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/dbio.1993.1040" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Philip1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Philip, N., Auger, M., Mattei, J. F., Giraud, F.
|
|
<strong>Achondroplasia in sibs of normal parents.</strong>
|
|
J. Med. Genet. 25: 857-859, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3236371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3236371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3236371" 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.25.12.857" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Pierre-Kahn1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pierre-Kahn, A., Hirsch, J. F., Renier, D., Metzger, J., Maroteaux, P.
|
|
<strong>Hydrocephalus and achondroplasia: a study of 25 observations.</strong>
|
|
Child's Brain 7: 205-219, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7438842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7438842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7438842" 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="84" class="mim-anchor"></a>
|
|
<a id="Pulst1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pulst, S.-M., Graham, J. M., Jr., Fain, P., Barker, D., Pribyl, T., Korenberg, J. R.
|
|
<strong>The achondroplasia gene is not linked to the locus for neurofibromatosis 1 on chromosome 17.</strong>
|
|
Hum. Genet. 85: 12-14, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2162805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2162805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2162805" 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/BF00276318" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Pyeritz1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pyeritz, R. E., Sack, G. H., Jr., Udvarhelyi, G. B.
|
|
<strong>Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients.</strong>
|
|
Am. J. Med. Genet. 28: 433-444, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3425618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3425618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3425618" 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.1320280221" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Randolph1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Randolph, L. M., Shohat, M., Miller, D., Lachman, R., Rimoin, D. L.
|
|
<strong>Achondroplasia with ankylosing spondylitis.</strong>
|
|
Am. J. Med. Genet. 31: 117-121, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3223492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3223492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3223492" 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.1320310113" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Reiser1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reiser, C. A., Pauli, R. M., Hall, J. G.
|
|
<strong>Achondroplasia: unexpected familial recurrence.</strong>
|
|
Am. J. Med. Genet. 19: 245-250, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6507475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6507475</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6507475" 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.1320190206" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Reynolds2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reynolds, K. K., Modaff, P., Pauli, R. M.
|
|
<strong>Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 101: 40-45, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343336" 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.1307" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Rimoin1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rimoin, D. L., Hughes, G. N., Kaufman, R. L., Rosenthal, R. E., McAlister, W. H., Silberberg, R.
|
|
<strong>Endochondral ossification in achondroplastic dwarfism.</strong>
|
|
New Eng. J. Med. 283: 728-735, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4989392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4989392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4989392" 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/NEJM197010012831404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Rousseau1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A.
|
|
<strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong>
|
|
Nature 371: 252-254, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8078586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/371252a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Rump2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J.
|
|
<strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong>
|
|
Am. J. Med. Genet. 140A: 284-290, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411219" 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.31084" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Savarirayan2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Savarirayan, R., Irving, M., Bacino, C. A., Bostwick, B., Charrow, J., Cormier-Daire, V., Sang, K.-H. L. Q., Dickson, P., Harmatz, P., Phillips, J., Owen, N., Cherukuri, A., Jayaram, K., Jeha, G. S., Larimore, K., Chan, M.-L., Labed, A. H., Day, J., Hoover-Fong, J.
|
|
<strong>C-type natriuretic peptide analogue therapy in children with achondroplasia.</strong>
|
|
New Eng. J. Med. 381: 25-35, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31269546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31269546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31269546" 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/NEJMoa1813446" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Shiang1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J.
|
|
<strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong>
|
|
Cell 78: 335-342, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7913883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Shohat1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shohat, M., Tick, D., Barakat, S., Bu, X., Melmed, S., Rimoin, D. L.
|
|
<strong>Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia.</strong>
|
|
J. Clin. Endocr. Metab. 81: 4033-4037, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8923856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8923856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8923856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.81.11.8923856" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Siebens1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Siebens, A. A., Hungerford, D. S., Kirby, N. A.
|
|
<strong>Curves of the achondroplastic spine: a new hypothesis.</strong>
|
|
Johns Hopkins Med. J. 142: 205-210, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/149212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">149212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=149212" 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="96" class="mim-anchor"></a>
|
|
<a id="Sobetzko2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A.
|
|
<strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong>
|
|
J. Med. Genet. 37: 958-959, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186940" 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.37.12.958" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Sommer1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sommer, A., Young-Wee, T., Frye, T.
|
|
<strong>Achondroplasia-hypochondroplasia complex.</strong>
|
|
Am. J. Med. Genet. 26: 949-957, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3591840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3591840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3591840" 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.1320260426" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Stanescu1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stanescu, R., Stanescu, V., Maroteaux, P.
|
|
<strong>Homozygous achondroplasia: morphologic and biochemical study of cartilage.</strong>
|
|
Am. J. Med. Genet. 37: 412-421, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2260574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2260574</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2260574" 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.1320370323" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Stoll1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stoll, C., Dott, B., Roth, M.-P., Alembik, Y.
|
|
<strong>Birth prevalence rates of skeletal dysplasias.</strong>
|
|
Clin. Genet. 35: 88-92, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785882</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2785882" 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.1399-0004.1989.tb02912.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Stoll2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stoll, C., Feingold, J.
|
|
<strong>Do parents and grandparents of patients with achondroplasia have a higher cancer risk?</strong>
|
|
Am. J. Med. Genet. 130A: 165-168, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15372518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15372518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15372518" 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.30273" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Stoll1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stoll, C., Roth, M.-P., Bigel, P.
|
|
<strong>A reexamination of parental age effect on the occurrence of new mutations for achondroplasia. In: Papadatos, C. J.; Bartsocas, C. S. (eds.): Skeletal Dysplasias.</strong>
|
|
New York: Alan R. Liss (pub.) 1982. Pp. 419-426.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Strom1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strom, C. M.
|
|
<strong>Achondroplasia due to DNA insertion into the type II collagen gene. (Abstract)</strong>
|
|
Pediat. Res. 18: 226A, 1984.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Superti-Furga1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B.
|
|
<strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong>
|
|
Europ. J. Pediat. 154: 215-219, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7758520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7758520</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7758520" 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/BF01954274" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Tasker1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tasker, R. C., Dundas, I., Laverty, A., Fletcher, M., Lane, R., Stocks, J.
|
|
<strong>Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study.</strong>
|
|
Arch. Dis. Child. 79: 99-108, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9797588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9797588</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9797588" 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/adc.79.2.99" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="105" class="mim-anchor"></a>
|
|
<a id="Thompson1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, J. N., Jr., Schaefer, G. B., Conley, M. C., Mascie-Taylor, C. G. N.
|
|
<strong>Achondroplasia and parental age. (Letter)</strong>
|
|
New Eng. J. Med. 314: 521-522, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3945286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3945286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3945286" 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/nejm198602203140820" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Tiemann-Boege2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tiemann-Boege, I., Navidi, W., Grewal, R., Cohn, D., Eskenazi, B., Wyrobek, A. J., Arnheim, N.
|
|
<strong>The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 14952-14957, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12397172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12397172</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12397172[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=12397172" 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.232568699" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Van Esch2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Fryns, J. P.
|
|
<strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong>
|
|
Genet. Counsel. 15: 375-377, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15517832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15517832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15517832" 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="108" class="mim-anchor"></a>
|
|
<a id="Velinov1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Velinov, M., Slaugenhaupt, S. A., Stoilov, I., Scott, C. I., Jr., Gusella, J. F., Tsipouras, P.
|
|
<strong>The gene for achondroplasia maps to the telomeric region of chromosome 4p.</strong>
|
|
Nature Genet. 6: 314-317, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8012397" 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/ng0394-314" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Verloes1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verloes, A., Massart, B., Jossa, V., Langhendries, J. P., Hainaut, H., Paquot, J. P., Koulischer, L.
|
|
<strong>Neuroblastoma in a dwarfed newborn: possible clue to the chromosomal localization of the gene for achondroplasia?</strong>
|
|
Ann. Genet. 34: 25-26, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1952787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1952787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1952787" 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="110" class="mim-anchor"></a>
|
|
<a id="Wadia1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wadia, R.
|
|
<strong>Achondroplasia in two first cousins.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 227-230, 1969.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Wallace1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Exton, L. A., Pritchard, D. A., Leung, Y., Cooke, R. A.
|
|
<strong>Severe achondroplasia: demonstration of probable heterogeneity within this clinical syndrome.</strong>
|
|
J. Med. Genet. 7: 22-26, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5480962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5480962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5480962" 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.7.1.22" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Waller2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waller, D. K., Correa, A., Vo, T. M., Wang, Y., Hobbs, C., Langlois, P. H., Pearson, K., Romitti, P. A., Shaw, G. M., Hecht, J. T.
|
|
<strong>The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.</strong>
|
|
Am. J. Med. Genet. 146A: 2385-2389, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18698630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18698630</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18698630" 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.32485" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Waters1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waters, K. A., Everett, F., Sillence, D. O., Fagan, E. R., Sullivan, C. E.
|
|
<strong>Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials.</strong>
|
|
Am. J. Med. Genet. 59: 460-466, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8585566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8585566</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8585566" 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.1320590412" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="114" class="mim-anchor"></a>
|
|
<a id="Weber1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weber, G., Prinster, C., Meneghel, M., Russo, F., Mora, S., Puzzovio, M., Del Maschio, M., Chiumello, G.
|
|
<strong>Human growth hormone treatment in prepubertal children with achondroplasia.</strong>
|
|
Am. J. Med. Genet. 61: 396-400, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8834055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8834055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8834055" 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/(SICI)1096-8628(19960202)61:4<396::AID-AJMG17>3.0.CO;2-N" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="Weinberg1912" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weinberg, W.
|
|
<strong>Zur Vererbung des Zwergwuchses.</strong>
|
|
Arch. Rass. Ges. Biol. 9: 710-717, 1912.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="116" class="mim-anchor"></a>
|
|
<a id="Woods1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Woods, C. G., Rogers, J. G., Mayne, V.
|
|
<strong>Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.</strong>
|
|
J. Med. Genet. 31: 565-569, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7966194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7966194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7966194" 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.31.7.565" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Wynn2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wynn, J., King, T. M., Gambello, M. J., Waller, D. K., Hecht, J. T.
|
|
<strong>Mortality in achondroplasia study: a 42-year follow-up.</strong>
|
|
Am. J. Med. Genet. 143A: 2502-2511, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17879967/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17879967</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17879967" 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.31919" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Yang1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yang, S. S., Corbett, D. P., Brough, A. J., Heidelberger, K. P., Bernstein, J.
|
|
<strong>Upper cervical myelopathy in achondroplasia.</strong>
|
|
Am. J. Clin. Path. 68: 68-72, 1977.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/868806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">868806</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=868806" 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/ajcp/68.1.68" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Yasoda2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K.
|
|
<strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong>
|
|
Nature Med. 10: 80-86, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14702637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14702637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14702637" 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/nm971" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="120" class="mim-anchor"></a>
|
|
<a id="Young1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Young, I. D., Ruggins, N. R., Somers, J. M., Zuccollo, J. M., Rutter, N.
|
|
<strong>Lethal skeletal dysplasia owing to a double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita.</strong>
|
|
J. Med. Genet. 29: 831-833, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1453438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1453438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1453438" 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.29.11.831" 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 : 07/09/2019
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 10/9/2013<br>Ada Hamosh - updated : 1/8/2013<br>Nara Sobreira - updated : 11/20/2009<br>Nara Sobreira - updated : 5/22/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 12/30/2008<br>Kelly A. Przylepa - updated : 5/5/2008<br>Marla J. F. O'Neill - updated : 4/30/2008<br>Marla J. F. O'Neill - updated : 3/2/2007<br>Marla J. F. O'Neill - updated : 11/10/2006<br>Marla J. F. O'Neill - updated : 3/7/2006<br>Cassandra L. Kniffin - updated : 2/8/2006<br>Victor A. McKusick - updated : 1/18/2006<br>Victor A. McKusick - updated : 1/12/2005<br>Victor A. McKusick - updated : 12/6/2004<br>Victor A. McKusick - updated : 11/23/2004<br>Marla J. F. O'Neill - updated : 6/30/2004<br>Victor A. McKusick - updated : 10/8/2003<br>Victor A. McKusick - updated : 5/16/2001<br>Michael J. Wright - updated : 2/6/2001<br>Armand Bottani - updated : 3/15/2000<br>Victor A. McKusick - updated : 2/24/2000<br>Paul Brennan - updated : 1/27/1999<br>Michael J. Wright - updated : 10/7/1998<br>Victor A. McKusick - updated : 10/9/1997<br>Victor A. McKusick - updated : 5/16/1997<br>John A. Phillips, III - updated : 4/1/1997<br>Victor A. McKusick - updated : 2/4/1997<br>Iosif W. Lurie - updated : 7/1/1996<br>Beat Steinmann - updated : 2/4/1994
|
|
</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 : 6/16/1986
|
|
</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 : 06/06/2024
|
|
</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 : 03/11/2021<br>carol : 07/10/2019<br>alopez : 07/09/2019<br>carol : 11/10/2016<br>carol : 03/02/2015<br>carol : 6/18/2014<br>carol : 10/9/2013<br>alopez : 1/8/2013<br>terry : 1/8/2013<br>terry : 1/13/2011<br>carol : 11/24/2009<br>terry : 11/20/2009<br>carol : 9/21/2009<br>carol : 5/22/2009<br>alopez : 4/16/2009<br>terry : 1/7/2009<br>wwang : 1/7/2009<br>ckniffin : 12/30/2008<br>wwang : 5/9/2008<br>carol : 5/5/2008<br>terry : 4/30/2008<br>wwang : 3/8/2007<br>wwang : 3/6/2007<br>terry : 3/2/2007<br>wwang : 11/13/2006<br>terry : 11/10/2006<br>wwang : 3/16/2006<br>wwang : 3/15/2006<br>terry : 3/7/2006<br>terry : 3/7/2006<br>wwang : 2/13/2006<br>ckniffin : 2/8/2006<br>alopez : 1/20/2006<br>terry : 1/18/2006<br>terry : 2/22/2005<br>terry : 2/18/2005<br>wwang : 1/19/2005<br>wwang : 1/13/2005<br>terry : 1/12/2005<br>alopez : 12/6/2004<br>tkritzer : 11/30/2004<br>terry : 11/23/2004<br>carol : 7/1/2004<br>carol : 7/1/2004<br>terry : 6/30/2004<br>terry : 6/2/2004<br>terry : 2/19/2004<br>terry : 2/19/2004<br>alopez : 11/3/2003<br>alopez : 10/8/2003<br>carol : 12/10/2002<br>tkritzer : 12/6/2002<br>terry : 12/4/2002<br>mcapotos : 5/23/2001<br>mcapotos : 5/22/2001<br>terry : 5/16/2001<br>alopez : 4/9/2001<br>alopez : 2/6/2001<br>carol : 3/15/2000<br>alopez : 2/28/2000<br>terry : 2/24/2000<br>terry : 4/29/1999<br>alopez : 1/27/1999<br>carol : 10/12/1998<br>terry : 10/9/1998<br>terry : 10/7/1998<br>dkim : 9/11/1998<br>terry : 6/3/1998<br>mark : 10/14/1997<br>terry : 10/9/1997<br>alopez : 7/9/1997<br>mark : 7/3/1997<br>mark : 5/16/1997<br>terry : 5/12/1997<br>alopez : 5/12/1997<br>jenny : 4/4/1997<br>jenny : 4/1/1997<br>joanna : 2/14/1997<br>joanna : 2/4/1997<br>terry : 12/17/1996<br>carol : 7/1/1996<br>mark : 4/11/1996<br>mark : 2/26/1996<br>mark : 2/26/1996<br>terry : 2/20/1996<br>mark : 1/17/1996<br>terry : 1/16/1996<br>mark : 7/19/1995<br>terry : 2/27/1995<br>carol : 1/18/1995<br>mimadm : 6/8/1994<br>warfield : 3/31/1994
|
|
</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> 100800
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ACHONDROPLASIA; ACH
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 86268005;
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q77.4;
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 15;
|
|
|
|
|
|
<strong>DO:</strong> 4480;
|
|
|
|
|
|
</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">
|
|
4p16.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Achondroplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
100800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
FGFR3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
134934
|
|
</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 achondroplasia (ACH) is caused by heterozygous mutation in the fibroblast growth factor receptor-3 gene (FGFR3; 134934) on chromosome 4p16.3.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Achondroplasia (ACH) is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by Bellus et al., 1995). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Whereas many conditions that cause short stature have inappropriately been called achondroplasia in the past, the phenotype of this osteochondrodysplasia is so distinctive and so easily identified clinically and radiologically at birth that confusion should not occur. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Hyperextensibility of most joints, especially the knees, is common, but extension and rotation are limited at the elbow. A thoracolumbar gibbus is typically present at birth, but usually gives way to exaggerated lumbar lordosis when the child begins to ambulate. Mild to moderate hypotonia is common, and motor milestones are usually delayed. Intelligence is normal unless hydrocephalus or other central nervous system complications arise. In 13 achondroplastic infants, Hecht et al. (1991) found that cognitive development was average and did not correlate with motor development which typically was delayed. It was noteworthy that reduced mental capacity correlated with evidence of respiratory dysfunction detected by polysomnography. </p><p>In children, caudad narrowing of the interpediculate distance, rather than the normal caudad widening, and a notchlike sacroiliac groove are typical radiologic features. Also in children, epiphyseal ossification centers show a circumflex or chevron seat on the metaphysis. Limb shortening is especially striking in the proximal segments, e.g., the humerus; hence the description rhizomelic ('root limb'). The radiologic features of true achondroplasia and much concerning the natural history of the condition were presented by Langer et al. (1967) on the basis of a study of 101 cases and by Hall (1988). </p><p>True megalencephaly occurs in achondroplasia and has been speculated to indicate effects of the gene other than those on the skeleton alone (Dennis et al., 1961). Disproportion between the base of the skull and the brain results in internal hydrocephalus in some cases. The hydrocephalus may be caused by increased intracranial venous pressure due to stenosis of the sigmoid sinus at the level of the narrowed jugular foramina (Pierre-Kahn et al., 1980). Hall et al. (1982) pointed out that the large head of the achondroplastic fetus creates an increased risk of intracranial bleeding during delivery. They recommended that in the management of achondroplastic infants ultrasonography be done at birth and at 2, 4, and 6 months of age to establish ventricular size, the presence or absence of hydrocephalus, and possible intracranial bleed. They stated the impression that some achondroplasts have only megalencephaly, others have true communicating hydrocephalus, and yet others have dilated ventricles without hydrocephalus. Nelson et al. (1988) concluded that brainstem compression is common in achondroplasia and may account in part for the abnormal respiratory function. </p><p>Pauli et al. (1984) focused attention on the risk of sudden unexpected death in infants with achondroplasia. While uncontrolled and retrospective, their study demonstrated an excess of deaths in the first year of life, most or all of which were attributable to abnormalities at the craniocervical junction. Hecht et al. (1987) showed that the excess risk of death in infants with achondroplasia may approach 7.5%, largely because of cervical cord compression. Pauli et al. (1995) performed a prospective assessment of risk for cervical medullary-junction compression in 53 infants, 5 of whom were judged to have sufficient craniocervical junction compression to require surgical decompression. Intraoperative observation showed marked abnormality of the cervical spinal cord, and all operated-on children showed marked improvement of neurologic function. The best predictors of need for suboccipital decompression included lower-limb hyperreflexia or clonus on examination, central hypopnea demonstrated by polysomnography, and foramen magnum measures below the mean for children with achondroplasia. </p><p>Lachman (1997) reviewed the neurologic abnormalities in the skeletal dysplasias from a clinical and radiologic perspective. Three important major groups were identified: (i) achondroplasia (cranio-cervical junction problems in infancy, spinal stenosis, and neurogenic claudication in adulthood); (ii) type II collagenopathies (upper cervical spine anatomic and functional problems); and (iii) craniotubular and sclerosing bone dysplasias (osseous overgrowth with foraminal obstruction problems). </p><p>To detect myelopathy, Boor et al. (1999) recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia. In addition to the conventional technique, they employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the craniocervical junction. The findings were correlated with the clinical status and MRI results. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia, and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. </p><p>Hecht et al. (1988) reviewed the subject of obesity in achondroplasia, concluding that it is a major problem which, whatever its underlying cause, aggravates the morbidity associated with lumbar stenosis and contributes to the nonspecific joint problems and to the possible early cardiovascular mortality in this condition. Using data about 409 Caucasian patients with achondroplasia from different countries (1,147 observations), Hunter et al. (1996) developed weight for height (W/H) curves for these patients. They showed that to a height of about 75 cm, the mean W/H curves are virtually identical for normal and achondroplastic children. After this height, the W/H curves for achondroplastic patients rise above those for the general population. Hunter et al. (1996) contended that the best estimation of weight excess for achondroplastic patients aged 3 to 6 years is given by the Quetelet index, whereas that for patients aged 6 to 18 years is the Rohrer index. </p><p>Homozygosity for the achondroplasia gene results in a severe disorder of the skeleton with radiologic changes qualitatively somewhat different from those of the usual heterozygous achondroplasia; early death results from respiratory embarrassment from the small thoracic cage and neurologic deficit from hydrocephalus (Hall et al., 1969). Yang et al. (1977) reported upper cervical myelopathy in a homozygote. </p><p>Horton et al. (1988) found that the epiphyseal and growth plate cartilages have a normal appearance histologically, and the major matrix constituents exhibit a normal distribution by immunostaining; however, morphometric investigations have indicated that the growth plate is shorter than normal and that the shortening is greater in homozygous than in heterozygous achondroplasia, suggesting a gene dosage effect. Stanescu et al. (1990) reported histochemical, immunohistochemical, electron microscopic, and biochemical studies on upper tibial cartilage from a case of homozygous achondroplasia. No specific abnormality was defined. Aterman et al. (1983) expressed puzzlement at the striking histologic changes in homozygous achondroplasia despite the virtual absence of changes in the heterozygote. They pointed out that histologic studies in the heterozygote at a few weeks or months of age have not been done. They suggested that because of similarities between what they called PHA (presumed homozygous achondroplasia) and thanatophoric dwarfism (187600), some cases of the latter condition may be due to a particularly severe mutation at the achondroplasia locus. </p><p>Young et al. (1992) described lethal short-limb dwarfism in the offspring of a father with spondyloepiphyseal dysplasia congenita (SEDC; 183900) and a mother with achondroplasia. Young et al. (1992) suggested that the infant was a double heterozygote for the 2 dominant genes rather than a compound heterozygote. It was considered unlikely that SEDC and achondroplasia are allelic because of the evidence that most, if not all, cases of SEDC result from mutation in the type II collagen gene (COL2A1; 120140), whereas this gene has been excluded as the site of the mutation in achondroplasia. </p><p>Evidence that hypochondroplasia (146000) can be caused by an allele at the achondroplasia locus came from observations of a presumed genetic compound in the offspring of an achondroplastic father and a hypochondroplastic mother who exhibited growth deficiency and radiographic abnormalities of the skeleton that were much more severe than those typically seen in achondroplasia (McKusick et al., 1973; Sommer et al., 1987) and somewhat less severe than those of the ACH homozygote. Huggins et al. (1999) reported an 8-month-old girl with achondroplasia/hypochondroplasia whose father had the G380R achondroplasia mutation (134934.0001) in the FGFR3 gene and whose mother had the N450K hypochondroplasia mutation (134934.0010). Chitayat et al. (1999) simultaneously reported an infant boy with achondroplasia/hypochondroplasia whose mother had the G380R mutation and whose father had the N450K mutation. Molecular analysis confirmed the compound heterozygosity of both children, who displayed an intermediate phenotype that was more severe than either condition in the heterozygous state but less severe than homozygous ACH. </p><p>In a presentation of adult genetic skeletal dysplasias found in the Museum of Pathological Anatomy in Vienna, Beighton et al. (1993) pictured the skeleton of a 61-year-old man with achondroplasia who died of transverse myelitis. Randolph et al. (1988) reported an achondroplastic patient who developed classic ankylosing spondylitis (106300). There is no fundamental connection between the 2 disorders. The importance of the observation is mainly to indicate that back problems in achondroplasts can be due to causes other than the underlying disease. </p><p>Hunter et al. (1998) presented data from a multicenter study of 193 individuals with achondroplasia. They found that 89.4% of children had at least one episode of otitis media within the first 2 years of life; 24 of 99 children who had otitis media in the first year of life had several infections. All were observed to have chronic otitis media; 78.3% of individuals required the insertion of ventilation tubes at some point in their lives. Thirty of 85 patients aged 1 to 2 years and 26 of 70 patients aged 2 to 3 years had received at least one set of ventilation tubes. A degree of conductive hearing loss was found in 38.3% of individuals at sometime in their lives, the majority of these being found after 4 years of age Tonsillectomy was performed in 38.8% of individuals, with cumulative rates of 8.8% within the first 4 years of life and 25% by age 8 years. Speech delay was found in 18.6% of individuals, and 10.9% had articulation problems; only 9.5% of these individuals received speech therapy. Orthodontic problems were found in 53.8% of individuals; only 3.2% of these individuals presented within the first 10 years of life. </p><p>Hunter et al. (1998) found that 10.5% of individuals had a ventricular shunt placed; all but one of these procedures were done in the preteenage years. Cervicomedullary decompression surgery had been performed in 6.8% of children by 4 years of age; however, this procedure was also performed in a number of older children, teenagers, and adults, with a total of 16.5% of individuals having this type of surgery. Apnea was reported in 10.9% of individuals by age 4 years and 16.1% of individuals overall. </p><p>Hunter et al. (1998) defined tibial bowing as a distance of greater than 5 cm between the knees, with the legs straight and ankles apposed. Using these criteria, they found that 9.7% of individuals had tibial bowing by age 5 years. This continued to develop throughout childhood and into adult life, with a total of 41.6% of individuals being affected at some time. Tibial osteotomy had been performed on 21.6% of these individuals. By age 10 years, 8.9% of individuals had neurologic signs in the leg; however, by the sixth decade, 77.9% of individuals had these signs. A total of 24.1% had surgery for spinal stenosis, with an additional 18% in whom the diagnosis was made but surgery had not been performed. A majority of these surgeries were performed in individuals over 40 years of age. Hunter et al. (1998) concluded that middle ear disease with its attendant risk of hearing loss was more frequent than previously reported, and that while a significant number of patients with achondroplasia experience delayed speech, only a minority receive speech therapy. The rate of early cervicomedullary decompression was comparable to the previously reported series, but an equivalent proportion of patients require such intervention beyond childhood. Hunter et al. (1998) also concluded that a significant number of patients have neurologic complaints by their teenage years and that this becomes a majority in adulthood. </p><p>Tasker et al. (1998) characterized cardiorespiratory and sleep dysfunction in 17 patients with achondroplasia referred to Great Ormond Street Hospital for Children, London. Three distinct etiologic groups were identified: group 1 had a mild degree of midfacial hypoplasia resulting in relative adenotonsillar hypertrophy; group 2 had jugular foramen stenosis resulting in muscular upper airway obstruction and progressive hydrocephalus due to jugular venous hypertension; and group 3 had muscular upper airway obstruction without hydrocephalus resulting from hypoglossal canal stenosis with or without foramen magnum compression. In addition, gastroesophageal reflux, which tended to occur in group 3 patients, was identified as a significant factor in the development of airway disease. Group 1 patients had obstructive sleep apnea only, and showed marked symptomatic improvement following adenotonsillectomy. Group 2 patients had central apnea responsive to surgical treatment of their hydrocephalus; obstructive sleep apnea in this group did not appear to respond to adenotonsillectomy, but to nocturnal continuous positive airway pressure. Group 3 patients had progressive cor pulmonale, obstructive and central sleep apnea, and gastroesophageal reflux with small airway pathology requiring multiple treatment modalities including foramen magnum decompression. </p><p>In 4 (3.2%) of 126 children with achondroplasia undergoing periodic evaluations at a bone dysplasia clinic, Pauli and Modaff (1999) identified a right-sided temporal bone abnormality involving absence of a roof over the jugular bulb, with bulging of the bulb into the middle ear cavity. In 2 patients, dark bluish-gray discoloration behind the tympanic membrane was noted, and temporal bone CT scan confirmed the presence of unilateral jugular bulb dehiscence. In a third patient, a large dehiscent jugular bulb was observed during exploratory tympanotomy; in a fourth patient, after brisk bleeding during attempted myringotomy and tube placement, CT scan demonstrated the absence of the bony covering of the jugular bulb. Jugular bulb dehiscence was suspected in a fifth patient with dark bluish discoloration behind the inferior quarter of the tympanic membrane, but confirmatory studies had not been performed at the time of the report. Pauli and Modaff (1999) noted that dehiscence of the jugular bulb is of clinical relevance, particularly in regard to difficult-to-control bleeding at myringotomy, and is associated with otherwise unexplained hearing loss, tinnitus, and self-audible bruits in children with achondroplasia. </p><p>Reynolds et al. (2001) retrospectively reviewed clinical and computed tomographic data in 71 infants with achondroplasia. They found no correlation between infantile hypotonia and foramen magnum size. These results suggested that there is no direct relationship and that foraminal size does not affect severity of hypotonia. They concluded that the only plausible explanation for the infantile hypotonia of achondroplasia is a primary effect of the causative mutation in FGFR3 (134934), which is expressed in brain. </p><p>Van Esch and Fryns (2004) described acanthosis nigricans in a 9-year-old boy with achondroplasia due to the classic gly380-to-arg mutation (134934.0001) in FGFR3. </p><p>Wynn et al. (2007) reported a 42-year follow-up study of mortality in achondroplasia. The study included 718 achondroplasia individuals from an earlier mortality study by Hecht et al. (1987) and 75 additional achondroplasia individuals. Rates of death were similar across the entire follow-up period. The overall mortality and age-specific mortality at all ages remained significantly increased. Accidental and neurologic disease-related deaths were increased in adults. Heart disease-related mortality, between ages 25 and 35, was more than 10 times higher than in the general population. Overall survival and the average life expectancy in this ACH population were decreased by 10 years. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Achondroplasia is inherited as an autosomal dominant with essentially complete penetrance. About seven-eighths of cases are the result of new mutation, there being a considerable reduction of effective reproductive fitness.</p><p>Paternal age effect on mutation was noted by Penrose (1955). Stoll et al. (1982) reported advanced paternal age in sporadic cases ascertained through the French counterpart of LPA (Little People of America), APPT (Association des Personnes de Petite Taille). Thompson et al. (1986) found that, on average, the severity of achondroplasia tends to be reduced with increasing parental age. It is doubtful that a recessive form of achondroplasia, indistinguishable from the dominant form, exists. Documentation of the diagnosis is inadequate in most reports of possible recessive inheritance. </p><p>Tiemann-Boege et al. (2002) performed direct molecular measurement of germline mutation frequency in sperm to test the hypothesis of paternal age effect on mutation. Using sperm DNA from donors of different ages, they determined the frequency of the 1138G-A mutation in the FGFR3 gene (134934.0001) that causes achondroplasia. The magnitude of the increase in mutation frequency with age was insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives were considered to explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and were inefficiently detected by the PCR assay used in the study. </p><p>Cohn and Weinberg (1956) reported affected twins with an affected sib. (This may have been achondrogenesis, e.g., 200600.) Chiari (1913) reported affected half sibs whose father had achondroplasia. Two first cousins, whose mothers were average-statured sisters, had undoubted achondroplasia (Wadia, 1969). Most dominants show sufficient variability to account for observations such as these on the basis of reduced penetrance but such is not the case with achondroplasia. </p><p>Gonadal mosaicism (or spermatogonial mutation) is a possible explanation for affected sibs from normal parents. Bowen (1974) described a possible instance of gonadal mosaicism; 2 daughters of normal parents had achondroplasia. One of the daughters had 2 children, one of whom was also achondroplastic. Fryns et al. (1983) reported 3 achondroplastic sisters born to normal parents. Philip et al. (1988) described the case of a man who had 3 daughters with classic achondroplasia, by 2 different women. </p><p>Henderson et al. (2000) reported sibs with achondroplasia born to average-statured parents. Both children had the 1138G-C causal mutation (134934.0002); this was also found in 28% of the unaffected mother's peripheral leukocytes. The authors therefore hypothesized that she was a germline as well as somatic mosaic for this mutation. </p><p>Sobetzko et al. (2000) also reported achondroplasia in a brother and sister with unaffected parents. The sibs shared the classic 1138G-A mutation (134934.0001) and also shared a 4p haplotype derived from the unaffected father. Paternal sperm was not available, and evidence of gonadal mosaicism could not be substantiated. </p><p>Affected cousins could be due to the coincidence of 2 independent mutations. Such was probably the case, in McKusick's opinion, in the second cousins once removed reported by Fitzsimmons (1985). Reiser et al. (1984) reviewed 6 families with unexpected familial recurrence and hypothesized that these recurrences were simply the result of 2 independent chance events. Dodinval and Le Marec (1987) reported 2 families, each with 2 cases of achondroplasia. In 1 family, a girl and her great aunt were affected; in the other, male and female first cousins. Both germinal mosaicism and paternal age effect appear to have their basis in the way spermatogonia are replenished, a feature that distinguishes gametogenesis in the male from that in the female. As outlined by Clermont (1966), spermatogonia go through a few mitotic divisions before embarking on the meiotic divisions that lead to mature sperm. Some of the products of the mitotic divisions are returned to the 'cell bank' to replenish the supply of spermatogonia. Mutations occurring during DNA replication can, therefore, accumulate, providing a basis for paternal age effect and for germinal mosaicism. Hoo (1984) suggested a small insertional translocation as a possible mechanism for recurrent achondroplasia in sibs with normal parents. In discussing 'male-driven evolution' and the evidence for a generally higher mutation rate in males than in females, Crow (1997) stated that the number of cell divisions required to generate sperm cells in a 30-year-old man is estimated at 400; the number of cell divisions that generate an egg is 24, irrespective of age. If mutation rates are proportional to the cell divisions, the male-to-female ratio should equal 17. In fact, the data show a higher ratio, as if mutation rates increase at a higher rate than the number of replications would predict--not surprising if fidelity of transcription and efficiency of repair mechanisms diminish with age. Studies in male and female birds by Ellegren and Fridolfsson (1997) appeared to support male-driven evolution of DNA sequences in birds. </p><p>The severe phenotype of the homozygote for the ACH gene and the possibility that hypochondroplasia represents an allelic disorder were discussed in connection with the discussion of clinical features of achondroplasia.</p><p>Langer et al. (1993) described a patient who was doubly heterozygous for achondroplasia and pseudoachondroplasia (177170). Woods et al. (1994) described a family in which the father had pseudoachondroplasia and the mother had achondroplasia, and 2 daughters were doubly affected and a son had achondroplasia only. At birth, the 2 daughters appeared to have achondroplasia. Later, the development of a fixed lumbar gibbus, unusual radiographic changes in the spine, increasing joint laxity of the hands, and characteristic gait and hand posture made the appearance of pseudoachondroplasia apparent. </p><p>Flynn and Pauli (2003) described a fourth case with radiologic findings virtually identical to those described by Langer et al. (1993) and Woods et al. (1994). They commented that the fact that all the probands were initially thought to have achondroplasia alone is not surprising, since pseudoachondroplastic features usually are not identifiable until after 2 years of age in affected individuals. The patient described by Langer et al. (1993) developed lumbar spinal stenosis at age 7.5 years. Both sibs in the report of Woods et al. (1994) had sufficiently severe stenosis of the foramen magnum to cause high cervical myelopathy requiring decompression. </p><p>Flynn and Pauli (2003) described a family in which the proband, her mother, and her maternal grandfather were all double heterozygotes for achondroplasia and for osteogenesis imperfecta type I (166200). Radiographic and clinical examination demonstrated features of both conditions, with neither being more prominent than would be expected for an individual heterozygous for each disorder alone. </p><p>Because of gonadal mosaicism, the risk of recurrence of achondroplasia in the sibs of achondroplastic children with unaffected parents is presumably higher than twice the mutation rate, but had not been measured. Mettler and Fraser (2000) collected data from 11 Canadian genetics centers and arrived at an estimate of 1 in 443, or 0.02%. </p><p>Stoll and Feingold (2004) performed analyses to determine whether a connection between teratogenesis and carcinogenesis is indicated by a higher cancer risk in parents of children with congenital anomalies. In achondroplasia, the new mutations are of paternal origin, raising the hypothesis of the existence of a 'mutator' gene acting in male meiosis and in somatic, mitotic cells in both sexes, which may favor the occurrence of cancer. By a questionnaire survey involving 76 males and 72 females with achondroplasia, Stoll and Feingold (2004) found that paternal grandfathers and grandmothers had significantly more cancers (56) than maternal grandfathers and grandmothers (24) (chi square = 14.80, p less than 0.001). </p><p>In 3 sibs who were the product of the first and third pregnancies of healthy nonconsanguineous parents, Natacci et al. (2008) identified heterozygosity for the G380R mutation in the FGFR3 gene (134934.0001). The mutation was not found in lymphocytic DNA from the parents; however, DNA analysis of a sperm sample from the 37-year-old father showed the G380R mutation. The authors stated that this was the second reported case of germinal mosaicism causing recurrent achondroplasia in a subsequent conception. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By linkage studies using DNA markers, Velinov et al. (1994) and Le Merrer et al. (1994) mapped the gene for achondroplasia and hypochondroplasia to the distal area of the short arm of chromosome 4 (4p16.3). Francomano et al. (1994) likewise mapped the ACH gene to 4p16.3, using 18 multigenerational families with achondroplasia and 8 anonymous dinucleotide repeat polymorphic markers from this region. No evidence of genetic heterogeneity was found. Analysis of a recombinant family localized the ACH locus to the 2.5-Mb region between D4S43 and the telomere. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
|
Francomano and Pyeritz (1988) excluded COL2A1 as the site of the mutation in achondroplasia by use of probes spanning the gene in an analysis of genomic DNA from 49 affected persons and 2 multiplex families. No gross rearrangements were seen on Southern blot analysis, and linkage studies in the multiplex families demonstrated discordant inheritance of achondroplasia and COL2A1 alleles. Evidence against linkage to COL2A1 has been presented before by Ogilvie et al. (1986). From their studies, Finkelstein et al. (1991) concluded that mutations at the chondroitin sulfate proteoglycan core protein (CSPGP) locus do not cause achondroplasia or pseudoachondroplasia (177170). </p><p>Edwards et al. (1988) commented on a report, made at the national meeting of the Neurofibromatosis Foundation, of 2 individuals with achondroplasia and neurofibromatosis (162200) who had translocations involving the long arm of chromosome 17. In both cases the breakpoint was at the region consistent with localization of the neurofibromatosis gene by linkage studies; a third case of coincident achondroplasia and neurofibromatosis was also mentioned. Korenberg et al. (1989) and Pulst et al. (1990) demonstrated by linkage analysis that the achondroplasia locus does not map between the 2 groups of markers flanking the gene for neurofibromatosis-1 on human chromosome 17. Verloes et al. (1991) observed connatal neuroblastoma in an infant with achondroplasia and suggested that the achondroplasia gene may be located on the short arm of chromosome 1 where a neuroblastoma locus (see 256700) appears to be situated. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Once the gene for achondroplasia was assigned to 4p16.3 by linkage analysis (Le Merrer et al., 1994; Velinov et al., 1994; Francomano et al., 1994), causative mutations were identified by the candidate gene approach and reported within 6 months of the first mapping report. Mutations in the gene for fibroblast growth factor receptor-3 (134934) were identified by Shiang et al. (1994) and independently by Rousseau et al. (1994). The FGFR3 gene had previously been mapped to the same region, 4p16.3, as the ACH gene and the Huntington disease gene. The mutation in 15 of the 16 achondroplasia-affected chromosomes studied by Shiang et al. (1994) was the same, a G-to-A transition at nucleotide 1138 (134934.0001) of the cDNA. The mutation on the only other ACH-affected chromosome 4 without the G-to-A transition at nucleotide 1138 had a G-to-C transversion at this same position (134934.0002). Both mutations resulted in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3. The mutation was located in a CpG dinucleotide. Rousseau et al. (1994) found the G380R mutation in all cases studied: 17 sporadic cases and 6 unrelated familial cases. Because of the high mutation rate, it might have been predicted that the achondroplasia gene is large and that any one of many mutations could lead to the same or a similar (hypochondroplasia) phenotype. Such is apparently not the case. The fact that there are no reports of Wolf-Hirschhorn syndrome (194190) patients with stigmata of achondroplasia may indicate that the phenotype is due to some mechanism other than haploinsufficiency, e.g., represents a dominant-negative or gain-of-function effect. (The independent work of Shiang et al. (1994) and Rousseau et al. (1994) was reported in the 29 July issue of Cell and the 15 September issue of Nature, respectively.) </p><p>Bellus et al. (1995) found that 150 of 154 unrelated achondroplasts had the G-to-A transition (134934.0001) and 3 had the G-to-C transversion (134934.0002) at nucleotide 1138 of the FGFR3 gene. All 153 had the gly380-to-arg substitution; in one individual, an atypical case, the gly380-to-arg substitution was missing. Nucleotide 1138 of the FGFR3 gene was the most mutable nucleotide in the human genome discovered at that time. Superti-Furga et al. (1995) reported the case of a newborn with achondroplasia who did not carry the mutation at nucleotide 1138 changing glycine-380 to arginine but had a mutation causing substitution of a nearby glycine with a cysteine (134934.0003). </p><p>The FGFR3 gene was isolated and studied in connection with a search for the Huntington disease gene. The distribution of FGFR3 mRNA in embryonic mouse tissues was found to be more restricted than that of FGFR1 (136350) and FGFR2 (176943) mRNA. Outside of the developing central nervous system, the highest level of FGFR3 mRNA was found to be in the prebone cartilage rudiments of all bones, and during endochondral ossification, FGFR3 was detected in resting but not hypertrophic cartilage (Peters et al., 1993). The glycine-to-arginine substitution would have a major effect on the structure, function, or both of the hydrophobic transmembrane domain and most likely would have a significant effect on the function of the receptor. Five of 6 ACH homozygotes were homozygous for the G-to-A transition and each of 6 sporadic cases, including the parents of 2 of the homozygotes, were heterozygous for the 1138A allele and the wildtype allele. The fact that FGFR3 transcripts are present in fetal and adult brain (which has the highest levels of any tissue) may have relevance in connection with the megalencephaly which is thought to occur in achondroplasia (Dennis et al., 1961). </p><p>FGFR3 codes for at least 2 isoforms of the gene product by alternate use of 2 different exons that encode the last half of the third immunoglobulin domain (IgIII), which is primarily responsible for the ligand-binding specificity. The isoforms are preferentially activated by the various fibroblast growth factors.</p><p>Rump et al. (2006) reported a Dutch infant with a severe form of achondroplasia caused by 2 de novo mutations in the FGFR3 gene on the same allele: the common G380R mutation (134934.0001) and L377R (134934.0027). Allele-specific PCR analysis confirmed that the 2 mutations were in cis. From birth, the child had severe respiratory difficulties with multiple hypoxic episodes due to a combination of upper airway obstruction, pulmonary hypoplasia, and cervicomedullary compression. He eventually became ventilator dependent and died at age 4 months. </p><p>Horton (2006) reviewed work on the nature of the basic defect in achondroplasia. After mutations in FGFR3 were identified as the basis of achondroplasia in 1994, attention turned to how the mutation disturbed linear bone growth. Biochemical studies of the FGFR3 receptor combined with knockout experiments in mice revealed that FGFR3 is a negative regulator of chondrocyte proliferation and differentiation in the growth plate and that the mutations in achondroplasia and related disorders activate the receptor. Thus they can be viewed as gain-of-function mutations. </p><p>Heuertz et al. (2006) screened 18 exons of the FGFR3 gene in 25 patients with hypochondroplasia and 1 with achondroplasia in whom the common mutations G380R and N540K had been excluded. The authors identified 7 novel missense mutations, including 1 in the patient with achondroplasia (S279C; 134934.0030). Heuertz et al. (2006) noted that 4 of the 6 extracellular mutations created additional cysteine residues and were associated with severe phenotypes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The diagnosis is based on the typical clinical and radiologic features; the delineation from severe hypochondroplasia may be arbitrary.</p><p>The demonstration of a very limited number of mutations causing achondroplasia and the ease with which they can be detected (1 PCR and 1 restriction digest) provides a simple method for prenatal diagnosis of ACH homozygotes in families at risk and in which the parents are heterozygous for either the 1138A or 1138C allele (Shiang et al., 1994). Shiang et al. (1994) expressed the opinion that other than the screening of at-risk pregnancies for homozygous ACH fetuses, any 'other application of the diagnostic test for ACH mutations should be prohibited.' Bellus et al. (1994) practiced prenatal diagnosis by chorionic villus sampling at 10 weeks and 4 days of gestation, both parents having achondroplasia. Both parents and the fetus were shown to be heterozygous for the more common G-to-A transition. Homozygous achondroplasia was excluded. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Recommendations for follow-up and management were reviewed at the first international symposium on achondroplasia (Nicoletti et al., 1988) and by Horton and Hecht (1993). The recommendations included: measurements of growth and head circumference using growth curves standardized for achondroplasia (Horton et al., 1978); careful neurologic examinations (including CT, MRI, somatosensory evoked potentials and polysomnography) and surgical enlargement of the foramen magnum in cases of severe stenosis; management of frequent middle ear infections and dental crowding; measures to control obesity starting in early childhood; growth hormone therapy (Horton et al., 1992), which is still experimental, and lengthening of the limb bones; tibial osteotomy or epiphysiodesis of the fibular growth plate to correct bowing of the legs; lumbar laminectomy for spinal stenosis which typically manifests in early adulthood; delivery of pregnant women with achondroplasia by cesarean section; and prenatal detection of affected fetuses by ultrasound. </p><p>Hunter et al. (1996) recommended that achondroplastic children stay within 1 SD of the mean weight for height curves for achondroplasts. </p><p>Hoover-Fong et al. (2007) developed weight for age, gender-specific growth curves for children with achondroplasia from birth through 16 years. The charts were constructed from a longitudinal, retrospective, single observer cohort study of 334 individuals with achondroplasia. The investigators proposed that the charts could be used in conjunction with current height for age charts developed by Horton et al. (1978) and weight for height charts developed by Hunter et al. (1996). </p><p>Shohat et al. (1996) investigated the effect of recombinant human growth hormone (hGH) treatment on the growth rate and proportion of individuals with achondroplasia and hypochondroplasia. They studied 15 individuals over 24 months including 6 months of observation, 12 months of hGH therapy (0.04 mg/kg/day), and 6 months of post treatment growth rate determination. The mean growth rate during hGH treatment (5.3 +/- 1.6 cm) of achondroplasts was significantly increased compared to pretreatment (4.0 +/- 1.0 cm/year, P less than 0.01) and posttreatment periods (3.1 +/- 1.3 cm; P less than 0.001). In the 4 children with hypochondroplasia, the growth rate during hGH treatment was 7.0 +/- 2.4 cm/year and 4.9 +/- 1.5 cm/year during the pre- and posttreatment periods, respectively. In achondroplasts, there was a significant increase in growth rate of only the lower segment (from 1.1 +/- 1.6 cm/year to 3.1 +/- 1.2 cm/year, P less than 0.02). Unexpectedly, this treatment does not seem to have a lesser effect on limbs than on trunk growth rate and, therefore, during 1 year of treatment, does not increase body disproportion. </p><p>Waters et al. (1995) studied the results of treatment of obstructive sleep apnea in achondroplasia. Treatment included adenotonsillectomy, weight loss, and nasal-mask continuous positive airway pressure (CPAP). They observed improvements in measurements of disturbed sleep architecture and some evidence of improvement in neurologic function. </p><p>Weber et al. (1996) studied the effects of recombinant human growth hormone treatment in 6 prepubertal children with achondroplasia, ranging in age from 2 to 8 years. They were given a GH dose of 0.1 IU/kg/day subcutaneously. During the year of treatment the growth velocity increased from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from the slight advancement of bone age in 2 patients. Their findings confirmed the individual variability in the response to GH treatment. </p><p>Horton (2006) reviewed milestones in achondroplasia research. As the molecular pathogenesis of achondroplasia emerged, interest shifted to therapy intended to counter the effects of the overactive receptor. One strategy involved chemical inhibitors selected for the FGFR3 tyrosine kinase. A second relied on blocking antibodies to interfere with binding of FGF ligands to FGFR3 (Aviezer et al., 2003). A third possibility involved C-type natriuretic peptide (CNP; 600296) which had been shown by Yasoda et al. (2004) to downregulate FGF-induced activation of MAP kinase signaling pathways in growth plate chondrocytes and to counteract the effects of the achondroplasia mutation in mice. </p><p>In achondroplasia and thanatophoric dysplasia (187600), spinal canal and foramen magnum stenosis can cause serious neurologic complications. Matsushita et al. (2009) observed premature synchondrosis closure in the spine and cranial base in human cases of homozygous achondroplasia and thanatophoric dysplasia as well as in mouse models of achondroplasia. In both species, premature synchondrosis closure was associated with increased bone formation. Chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increased bone morphogenetic protein (Bmp) ligand (e.g., BMP7, 112267) mRNA expression and decreased Bmp antagonist (e.g., noggin, 602991) mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. The authors proposed that spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. </p><p>C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). Lorget et al. (2012) reported the pharmacologic activity of a 39-amino acid CNP analog (BMN 111) with an extended plasma half-life due to its resistance to neutral endopeptidase (NEP; 120520) digestion. In achondroplasia human growth plate chondrocytes, Lorget et al. (2012) demonstrated a decrease in the phosphorylation of extracellular signal-regulated kinases 1 (ERK1; 601795) and 2 (ERK2; 176948), confirming that this CNP analog inhibits FGF-mediated MAP kinase activation. Concomitantly, Lorget et al. (2012) analyzed the phenotype of Fgfr3(Y367C/+) mice and showed the presence of achondroplasia-related clinical features in this mouse model. Lorget et al. (2012) found that in Fgfr(Y367C) heterozygous mice, treatment with the CNP analog led to a significant recovery of bone growth. They also observed an increase in the axial and appendicular skeleton lengths and improvements in dwarfism-related clinical features including flattening of the skull, reduced crossbite, straightening of the tibias and femurs, and correction of the growth plate defect. Lorget et al. (2012) concluded that their results provided the proof of concept that BMN 111, a NEP-resistant CNP analog, might benefit individuals with achondroplasia and hypochondroplasia. </p><p>Savarirayan et al. (2019) reported the results of a phase 2 dose-finding and extension study of vosoritide (a biologic analog of C-type natriuretic peptide) given by once-daily subcutaneous injection in 35 children with achondroplasia aged 5 through 14 years. All patients had adverse events (most commonly injection-site reactions), and serious adverse events occurred in 4 of the 35 patients. Therapy was discontinued in 6 patients, in 1 due to an adverse event. During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed up to a dose of 15 mcg/kg, and a sustained increase was observed at doses of 15 and 30 mcg/kg for up to 42 months. There was no difference in efficacy or safety between the 15 and 30 mcg/kg doses, which supported the choice of the lower dose for further evaluations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Early estimates on the prevalence of achondroplasia are undoubtedly incorrect because of misdiagnosis. For example, Wallace et al. (1970) reported 2 female sibs as examples of achondroplasia; both died in the neonatal period and showed, in addition to chondrodystrophy, central harelip, hypoplastic lungs, and hydrocephalus. Without radiographic studies it is impossible to identify the nature of this condition, but it is certainly not true achondroplasia; Jeune asphyxiating thoracic dystrophy (208500), thanatophoric dwarfism (187600), and achondrogenesis are each possibilities. </p><p>Using modern diagnostic criteria, Gardner (1977) estimated the mutation rate at 0.000014. Orioli et al. (1986) reported on the frequency of skeletal dysplasias among 349,470 births (live and stillbirths). The prevalence rate for achondroplasia was between 0.5 and 1.5/10,000 births. The mutation rate was estimated to be between 1.72 and 5.57 x 10(-5) per gamete per generation. The stated range is a consequence of the uncertainty of diagnosis in some cases. (The thanatophoric dysplasia/achondrogenesis group had a prevalence between 0.2 and 0.5/10,000 births. Osteogenesis imperfecta had a prevalence of 0.4/10,000 births. Only 1 case of diastrophic dysplasia was identified.) In the county of Fyn in Denmark, Andersen and Hauge (1989) determined the prevalence of generalized bone dysplasias by study of all children born in a 14-year period. The figures, which they referred to as 'point-prevalence at birth,' showed that achondroplasia was less common than generally thought (1.3 per 100,000), while osteogenesis imperfecta (21.8), multiple epiphyseal dysplasia tarda (9.0), achondrogenesis (6.4), osteopetrosis (5.1), and thanatophoric dysplasia (3.8) were found to be more frequent. Stoll et al. (1989) found a mutation rate of 3.3 x 10(-5) per gamete per generation. In Spain, Martinez-Frias et al. (1991) found a frequency of achondroplasia of 2.53 per 100,000 live births. Total prevalence of autosomal dominant malformation syndromes was 12.1 per 100,000 live births. </p><p>Using data from 7 population-based birth defects monitoring programs in the United States, Waller et al. (2008) estimated the prevalence of achondroplasia and thanatophoric dysplasia and presented data on the association between older paternal age and these conditions. The prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 live births (1/27,780-1/16,670 live births). The prevalence of thanatophoric dysplasia ranged from 0.21 to 0.30 per 10,000 live births (1/33.330-1/47,620). The data suggested that thanatophoric dysplasia is one-third to one-half as frequent as achondroplasia. The differences in the prevalence of these conditions across monitoring programs were consistent with random fluctuation. In Texas, fathers that were 25-29, 30-34, 35-39, and over 40 years of age had significantly increased rates of de novo achondroplasia and thanatophoric dysplasia among their offspring compared with younger fathers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>It is of historic interest that Weinberg (1912), of Hardy-Weinberg law fame, noted in the data collected by Rischbieth and Barrington that sporadic cases were more often last-born than first-born. The studies by Morch (1941) in Denmark and by Hobaek (1961) were early examples of full population studies.</p><p>Kozma (2006) described some of the earliest biologic evidence of dwarfism from ancient Egypt, dating as far back as 4500 BCE. Due to the hot, dry climate and natural and artificial mummification, Egypt is a major source of archeological information on achondroplasia. </p><p>Bernal and Briceno (2006) examined pottery artifacts from the Tumaco-La Tolita culture, which existed on the border of present-day Colombia and Ecuador approximately 2,500 years ago, and described a figurine consisting of head, thorax, and arms, which showed a cranial deformation, prominent forehead, low nasal bridge, jaw prognathism, and short neck, characteristics suggestive of achondroplasia. Bernal and Briceno (2006) believed these artifacts to be among the earliest artistic representations of disease. </p><p>Kozma (2008) provided a detailed historical review of skeletal dysplasias, particularly achondroplasia, in ancient Egypt. </p><p>Strom (1984) and Eng et al. (1985) purported to find abnormality of the type II collagen gene in achondroplasia. If such a defect is present, one might expect ocular abnormality in achondroplasia inasmuch as type II collagen is present in vitreous. SED congenita was a more plausible candidate for a structural defect of type II collagen because it is a dominant disorder that combines skeletal dysplasia with vitreous degeneration and deafness (experimental studies with antibodies to type II collagen indicate that this collagen type is represented in the middle ear); subsequently, defects were in fact found in the COL2A1 gene in SEDC. The report by Eng et al. (1985) was withdrawn in 1986 because figures, 'which were generated in the laboratory of C. Strom and C. Eng, were improperly assembled and therefore cannot be used to support the conclusions of the article.' </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Beighton and Bathfield (1981); Cohen et al. (1967); Durr (1968);
|
|
Elejalde et al. (1983); Fremion et al. (1984); Hall et al. (1979);
|
|
Maroteaux and Lamy (1964); Morgan and Young (1980); Murdoch et al.
|
|
(1970); Oberklaid et al. (1979); Opitz (1984); Pauli et al. (1983);
|
|
Penrose (1957); Pyeritz et al. (1987); Rimoin et al. (1970); Siebens
|
|
et al. (1978)
|
|
</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">
|
|
Andersen, P. E., Jr., Hauge, M.
|
|
<strong>Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey.</strong>
|
|
J. Med. Genet. 26: 37-44, 1989.
|
|
|
|
|
|
[PubMed: 2783977]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.26.1.37]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aterman, K., Welch, J. P., Taylor, P. G.
|
|
<strong>Presumed homozygous achondroplasia: a review and report of a further case.</strong>
|
|
Path. Res. Pract. 178: 27-39, 1983.
|
|
|
|
|
|
[PubMed: 6359101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0344-0338(83)80082-X]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aviezer, D., Golembo, M., Yayon, A.
|
|
<strong>Fibroblast growth factor receptor-3 as a therapeutic target for achondroplasia--genetic short limbed dwarfism.</strong>
|
|
Curr. Drug Targets 4: 353-365, 2003.
|
|
|
|
|
|
[PubMed: 12816345]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2174/1389450033490993]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beighton, P., Bathfield, C. A.
|
|
<strong>Gibbal achondroplasia.</strong>
|
|
J. Bone Joint Surg. Br. 63: 328-329, 1981.
|
|
|
|
|
|
[PubMed: 7263742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1302/0301-620X.63B3.7263742]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beighton, P., Sujansky, E., Patzak, B., Portele, K. A.
|
|
<strong>Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.</strong>
|
|
Am. J. Med. Genet. 47: 843-847, 1993.
|
|
|
|
|
|
[PubMed: 8279481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320470609]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Escallon, C. S., de Luna, R. O., Shumway, J. B., Blakemore, K. J., McIntosh, I., Francomano, C. A.
|
|
<strong>First-trimester prenatal diagnosis in couple at risk for homozygous achondroplasia. (Letter)</strong>
|
|
Lancet 344: 1511-1512, 1994.
|
|
|
|
|
|
[PubMed: 7968151]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(94)90332-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A.
|
|
<strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong>
|
|
Am. J. Hum. Genet. 56: 368-373, 1995.
|
|
|
|
|
|
[PubMed: 7847369]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernal, J. E., Briceno, I.
|
|
<strong>Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.</strong>
|
|
Clin. Genet. 70: 188-191, 2006.
|
|
|
|
|
|
[PubMed: 16922718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00670.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boor, R., Fricke, G., Bruhl, K., Spranger, J.
|
|
<strong>Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia.</strong>
|
|
Europ. J. Pediat. 158: 662-667, 1999.
|
|
|
|
|
|
[PubMed: 10445347]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004310051172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowen, P.
|
|
<strong>Achondroplasia in two sisters with normal parents.</strong>
|
|
Birth Defects Orig. Art. Ser. X(12): 31-36, 1974.
|
|
|
|
|
|
[PubMed: 4461062]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chiari, H.
|
|
<strong>Ueber familiaere Chondrodystrophia foetalis.</strong>
|
|
Muench. Med. Wschr. 60: 248-249, 1913.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D.
|
|
<strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong>
|
|
Am. J. Med. Genet. 84: 401-405, 1999.
|
|
|
|
|
|
[PubMed: 10360393]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clermont, Y.
|
|
<strong>Renewal of spermatogonia in man.</strong>
|
|
Am. J. Anat. 118: 509-524, 1966.
|
|
|
|
|
|
[PubMed: 5917196]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/aja.1001180211]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cohen, M. E., Rosenthal, A. D., Matson, D. D.
|
|
<strong>Neurological abnormalities in achondroplastic children.</strong>
|
|
J. Pediat. 71: 367-376, 1967.
|
|
|
|
|
|
[PubMed: 5298504]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(67)80296-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cohn, S., Weinberg, A.
|
|
<strong>Identical hydrocephalic achondroplastic twins. Subsequent delivery of single sibling with same abnormality.</strong>
|
|
Am. J. Obstet. Gynec. 72: 1346-1348, 1956.
|
|
|
|
|
|
[PubMed: 13372616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9378(56)90797-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crow, J. F.
|
|
<strong>Molecular evolution--who is in the driver's seat?</strong>
|
|
Nature Genet. 17: 129-130, 1997.
|
|
|
|
|
|
[PubMed: 9326921]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1097-129]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dennis, J. P., Rosenberg, H. S., Alvord, E. C., Jr.
|
|
<strong>Megalencephaly, internal hydrocephalus and other neurological aspects of achondroplasia.</strong>
|
|
Brain 84: 427-445, 1961.
|
|
|
|
|
|
[PubMed: 13885465]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/84.3.427]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dodinval, P., Le Marec, B.
|
|
<strong>Genetic counselling in unexpected familial recurrence of achondroplasia.</strong>
|
|
Am. J. Med. Genet. 28: 949-954, 1987.
|
|
|
|
|
|
[PubMed: 3688033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320280421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Durr, D. K.
|
|
<strong>Eine neue Dysostoseform mit Mikromelie bei zwei Geschwistern.</strong>
|
|
Helv. Paediat. Acta 23: 184-194, 1968.
|
|
|
|
|
|
[PubMed: 5699022]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Edwards, J. H., Huson, S., Ponder, B.
|
|
<strong>Neurofibromatosis. (Letter)</strong>
|
|
Lancet 332: 330 only, 1988. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 2899736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(88)92377-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elejalde, B. R., Elejalde, M. M., Hamilton, P. R., Lombardi, J. N.
|
|
<strong>Prenatal diagnosis in two pregnancies of an achondroplastic woman.</strong>
|
|
Am. J. Med. Genet. 15: 437-439, 1983.
|
|
|
|
|
|
[PubMed: 6881210]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320150308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellegren, H., Fridolfsson, A.-K.
|
|
<strong>Male-driven evolution of DNA sequences in birds.</strong>
|
|
Nature Genet. 17: 182-184, 1997.
|
|
|
|
|
|
[PubMed: 9326938]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1097-182]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eng, C. E. L., Pauli, R. M., Strom, C. M.
|
|
<strong>Nonrandom association of a type II procollagen genotype with achondroplasia.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 5465-5469, 1985. Note: Retraction: Proc. Nat. Acad. Sci. 83:5354 only, 1986.
|
|
|
|
|
|
[PubMed: 2991928]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.16.5465]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Finkelstein, J. E., Doege, K., Yamada, Y., Pyeritz, R. E., Graham, J. M., Jr., Moeschler, J. B., Pauli, R. M., Hecht, J. T., Francomano, C. A.
|
|
<strong>Analysis of the chondroitin sulfate proteoglycan core protein (CSPGP) gene in achondroplasia and pseudoachondroplasia.</strong>
|
|
Am. J. Hum. Genet. 48: 97-102, 1991.
|
|
|
|
|
|
[PubMed: 1670752]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fitzsimmons, J. S.
|
|
<strong>Familial recurrence of achondroplasia.</strong>
|
|
Am. J. Med. Genet. 22: 609-613, 1985.
|
|
|
|
|
|
[PubMed: 4061493]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320220320]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Flynn, M. A., Pauli, R. M.
|
|
<strong>Double heterozygosity in bone growth disorders: four new observations and review.</strong>
|
|
Am. J. Med. Genet. 121A: 193-208, 2003.
|
|
|
|
|
|
[PubMed: 12923858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20143]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Ortiz de Luna, R. I., Hefferon, T. W., Bellus, G. A., Turner, C. E., Taylor, E., Meyers, D. A., Blanton, S. H., Murray, J. C., McIntosh, I., Hecht, J. T.
|
|
<strong>Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p.</strong>
|
|
Hum. Molec. Genet. 3: 787-792, 1994.
|
|
|
|
|
|
[PubMed: 8081365]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.5.787]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Pyeritz, R. E.
|
|
<strong>Achondroplasia is not caused by mutation in the gene for type II collagen.</strong>
|
|
Am. J. Med. Genet. 29: 955-961, 1988.
|
|
|
|
|
|
[PubMed: 2899976]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320290433]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fremion, A. S., Garg, B. P., Kalsbeck, J.
|
|
<strong>Apnea as the sole manifestation of cord compression in achondroplasia.</strong>
|
|
J. Pediat. 104: 398-401, 1984.
|
|
|
|
|
|
[PubMed: 6707795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(84)81103-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fryns, J. P., Kleczkowska, A., Verresen, H., van den Berghe, H.
|
|
<strong>Germinal mosaicism in achondroplasia: a family with 3 affected siblings of normal parents.</strong>
|
|
Clin. Genet. 24: 156-158, 1983.
|
|
|
|
|
|
[PubMed: 6627718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1983.tb02232.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gardner, R. J. M.
|
|
<strong>A new estimate of the achondroplasia mutation rate.</strong>
|
|
Clin. Genet. 11: 31-38, 1977.
|
|
|
|
|
|
[PubMed: 830446]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb01274.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Dorst, J. P., Taybi, H., Scott, C. I., Jr., Langer, L. O., Jr., McKusick, V. A.
|
|
<strong>Two probable cases of homozygosity for the achondroplasia gene.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 24-34, 1969.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Golbus, M. S., Graham, C. B., Pagon, R. A., Luthy, D. A., Filly, R. A.
|
|
<strong>Failure of early prenatal diagnosis in classic achondroplasia.</strong>
|
|
Am. J. Med. Genet. 3: 371-375, 1979.
|
|
|
|
|
|
[PubMed: 474637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320030408]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. G., Horton, W., Kelly, T., Scott, C. I.
|
|
<strong>Head growth in achondroplasia: use of ultrasound studies. (Letter)</strong>
|
|
Am. J. Med. Genet. 13: 105, 1982.
|
|
|
|
|
|
[PubMed: 7137217]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320130116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, J. G.
|
|
<strong>The natural history of achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 3-10.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Francomano, C. A., Horton, W. A., Annegers, J. F.
|
|
<strong>Mortality in achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 41: 454-464, 1987.
|
|
|
|
|
|
[PubMed: 3631079]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Hood, O. J., Schwartz, R. J., Hennessey, J. C., Bernhardt, B. A., Horton, W. A.
|
|
<strong>Obesity in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 31: 597-602, 1988.
|
|
|
|
|
|
[PubMed: 3228140]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320310314]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hecht, J. T., Thompson, N. M., Weir, T., Patchell, L., Horton, W. A.
|
|
<strong>Cognitive and motor skills in achondroplastic infants: neurologic and respiratory correlates.</strong>
|
|
Am. J. Med. Genet. 41: 208-211, 1991.
|
|
|
|
|
|
[PubMed: 1785636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320410215]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B.
|
|
<strong>Germline and somatic mosaicism in achondroplasia.</strong>
|
|
J. Med. Genet. 37: 956-958, 2000.
|
|
|
|
|
|
[PubMed: 11186939]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.37.12.956]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J.
|
|
<strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong>
|
|
Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.
|
|
|
|
|
|
[PubMed: 16912704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hobaek, A.
|
|
<strong>Problems of Hereditary Chondrodysplasia.</strong>
|
|
Oslo: Oslo Univ. Press (pub.) 1961.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoo, J. J.
|
|
<strong>Alternative explanations for recurrent achondroplasia in siblings with normal parents.</strong>
|
|
Clin. Genet. 25: 553-554, 1984.
|
|
|
|
|
|
[PubMed: 6733952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00501.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoover-Fong, J. E., McGready, J., Schulze, K. J., Barnes, H., Scott, C. I.
|
|
<strong>Weight for age charts for children with achondroplasia.</strong>
|
|
Am. J. Med. Genet. 143A: 2227-2235, 2007.
|
|
|
|
|
|
[PubMed: 17764078]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31873]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hecht, J. T., Hood, O. J., Marshall, R. N., Moore, W. V., Hollowell, J. G.
|
|
<strong>Growth hormone therapy in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 42: 667-670, 1992.
|
|
|
|
|
|
[PubMed: 1632435]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320420508]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hecht, J. T.
|
|
<strong>The chondrodysplasias. In: Royce, P. M.; Steinmann, B. (eds.): Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects.</strong>
|
|
New York: Wiley-Liss (pub.) 1993. Pp. 641-675.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Hood, O. J., Machado, M. A., Campbell, D.
|
|
<strong>Growth plate cartilage studies in achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 81-89.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A., Rotter, J. I., Rimoin, D. L., Scott, C. L., Hall, J. G.
|
|
<strong>Standard growth curves for achondroplasia.</strong>
|
|
J. Pediat. 93: 435-438, 1978.
|
|
|
|
|
|
[PubMed: 690757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(78)81152-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horton, W. A.
|
|
<strong>Recent milestones in achondroplasia research.</strong>
|
|
Am. J. Med. Genet. 140A: 166-169, 2006.
|
|
|
|
|
|
[PubMed: 16353253]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31029]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T.
|
|
<strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong>
|
|
Am. J. Med. Genet. 84: 396-400, 1999.
|
|
|
|
|
|
[PubMed: 10360392]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hunter, A. G. W., Bankier, A., Rogers, J. G., Sillence, D., Scott, C. I., Jr.
|
|
<strong>Medical complications of achondroplasia: a multicentre patient review.</strong>
|
|
J. Med. Genet. 35: 705-712, 1998.
|
|
|
|
|
|
[PubMed: 9733026]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.35.9.705]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hunter, A. G. W., Hecht, J. T., Scott, Jr., C. I.
|
|
<strong>Standard weight for height curves in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 62: 255-261, 1996.
|
|
|
|
|
|
[PubMed: 8882783]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960329)62:3<255::AID-AJMG10>3.0.CO;2-J]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Korenberg, J. R., Barker, D., Fain, P., Graham, J., Pribyl, T., Pulst, S.-M.
|
|
<strong>Achondroplasia is not tightly linked to the locus for neurofibromatosis 1. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1025, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kozma, C.
|
|
<strong>Dwarfs in ancient Egypt.</strong>
|
|
Am. J. Med. Genet. 140A: 303-311, 2006.
|
|
|
|
|
|
[PubMed: 16380966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31068]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kozma, C.
|
|
<strong>Skeletal dysplasia in ancient Egypt.</strong>
|
|
Am. J. Med. Genet. 146A: 3104-3112, 2008.
|
|
|
|
|
|
[PubMed: 19006207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32501]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lachman, R. S.
|
|
<strong>Neurologic abnormalities in the skeletal dysplasias: a clinical and radiological perspective.</strong>
|
|
Am. J. Med. Genet. 69: 33-43, 1997.
|
|
|
|
|
|
[PubMed: 9066881]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19970303)69:1<33::aid-ajmg7>3.0.co;2-u]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Langer, L. O., Jr., Baumann, P. A., Gorlin, R. J.
|
|
<strong>Achondroplasia.</strong>
|
|
Am. J. Roentgen. Radium Ther. Nucl. Med. 100: 12-26, 1967.
|
|
|
|
|
|
[PubMed: 6023888]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2214/ajr.100.1.12]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Langer, L. O., Jr., Schaefer, G. B., Wadsworth, D. T.
|
|
<strong>Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.</strong>
|
|
Am. J. Med. Genet. 47: 772-781, 1993.
|
|
|
|
|
|
[PubMed: 8267011]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320470535]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Le Merrer, M., Rousseau, F., Legeai-Mallet, L., Landais, J.-C., Pelet, A., Bonaventure, J., Sanak, M., Weissenbach, J., Stoll, C., Munnich, A., Maroteaux, P.
|
|
<strong>A gene for achondroplasia--hypochondroplasia maps to chromosome 4p.</strong>
|
|
Nature Genet. 6: 318-321, 1994.
|
|
|
|
|
|
[PubMed: 8012398]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0394-318]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lorget, F., Kaci, N., Peng, J., Benoist-Lasselin, C., Mugniery, E., Oppeneer, T., Wendt, D. J., Bell, S. M., Bullens, S., Bunting, S., Tsuruda, L. S., O'Neill, C. A., Di Rocco, F., Munnich, A., Legeai-Mallet, L.
|
|
<strong>Evaluation of therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 91: 1108-1114, 2012.
|
|
|
|
|
|
[PubMed: 23200862]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2012.10.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maroteaux, P., Lamy, P.
|
|
<strong>Achondroplasia in man and animals.</strong>
|
|
Clin. Orthop. 33: 91-103, 1964.
|
|
|
|
|
|
[PubMed: 5889028]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martinez-Frias, M. L., Cereijo, A., Bermejo, E., Lopez, M., Sanchez, M., Gonzalo, C.
|
|
<strong>Epidemiological aspects of mendelian syndromes in a Spanish population sample: I. Autosomal dominant malformation syndromes.</strong>
|
|
Am. J. Med. Genet. 38: 622-625, 1991.
|
|
|
|
|
|
[PubMed: 2063907]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320380424]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S.
|
|
<strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong>
|
|
Hum. Molec. Genet. 18: 227-240, 2009.
|
|
|
|
|
|
[PubMed: 18923003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn339]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kelly, T. E., Dorst, J. P.
|
|
<strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong>
|
|
J. Med. Genet. 10: 11-16, 1973.
|
|
|
|
|
|
[PubMed: 4697848]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.10.1.11]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mettler, G., Fraser, F. C.
|
|
<strong>Recurrence risk for sibs of children with 'sporadic' achondroplasia.</strong>
|
|
Am. J. Med. Genet. 90: 250-251, 2000.
|
|
|
|
|
|
[PubMed: 10678665]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morch, E. T.
|
|
<strong>Chondrodystrophic dwarfs in Denmark.</strong>
|
|
Op. Ex Domo Biol. Hered. Hum. U. Hafniensis 3: 1-200, 1941.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morgan, D. F., Young, R. F.
|
|
<strong>Spinal neurological complications of achondroplasia: results of surgical treatment.</strong>
|
|
J. Neurosurg. 52: 463-472, 1980.
|
|
|
|
|
|
[PubMed: 7373371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3171/jns.1980.52.4.0463]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murdoch, J. L., Walker, B. A., Hall, J. G., Abbey, H., Smith, K. K., McKusick, V. A.
|
|
<strong>Achondroplasia--a genetic and statistical survey.</strong>
|
|
Ann. Hum. Genet. 33: 227-244, 1970.
|
|
|
|
|
|
[PubMed: 5504223]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1970.tb01648.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F.
|
|
<strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong>
|
|
Am. J. Med. Genet. 146A: 784-786, 2008.
|
|
|
|
|
|
[PubMed: 18266238]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nelson, F. W., Hecht, J. T., Horton, W. A., Butler, I. J., Goldie, W. D., Miner, M.
|
|
<strong>Neurological basis of respiratory complications in achondroplasia.</strong>
|
|
Ann. Neurol. 24: 89-93, 1988.
|
|
|
|
|
|
[PubMed: 3415202]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.410240117]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nicoletti, B., Kopits, S. E., Ascani, E., McKusick, V. A.
|
|
<strong>Human Achondroplasia: A Multidisciplinary Approach.</strong>
|
|
New York: Plenum Press (pub.) 1988. Pp. 3-9.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oberklaid, F., Danks, D. M., Jensen, F., Stace, L., Rosshandler, S.
|
|
<strong>Achondroplasia and hyperchondroplasia: comments on frequency, mutation rate, and radiological features in skull and spine.</strong>
|
|
J. Med. Genet. 16: 140-146, 1979.
|
|
|
|
|
|
[PubMed: 458831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.16.2.140]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ogilvie, D., Wordsworth, P., Thompson, E., Sykes, B.
|
|
<strong>Evidence against the structural gene encoding type II collagen (COL2A1) as the mutant locus in achondroplasia.</strong>
|
|
J. Med. Genet. 23: 19-22, 1986.
|
|
|
|
|
|
[PubMed: 3005580]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.23.1.19]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Opitz, J. M.
|
|
<strong>'Unstable premutation' in achondroplasia: penetrance vs phenotrance. (Editorial)</strong>
|
|
Am. J. Med. Genet. 19: 251-254, 1984.
|
|
|
|
|
|
[PubMed: 6507476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320190207]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orioli, I. M., Castilla, E. E., Barbosa-Neto, J. G.
|
|
<strong>The birth prevalence rates for the skeletal dysplasias.</strong>
|
|
J. Med. Genet. 23: 328-332, 1986.
|
|
|
|
|
|
[PubMed: 3746832]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.23.4.328]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Conroy, M. M., Langer, L. O., Jr., McLone, D. G., Naidich, T., Franciosi, R., Ratner, I. M., Copps, S. C.
|
|
<strong>Homozygous achondroplasia with survival beyond infancy.</strong>
|
|
Am. J. Med. Genet. 16: 459-473, 1983.
|
|
|
|
|
|
[PubMed: 6660245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320160404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Horton, V. K., Glinski, L. P., Reiser, C. A.
|
|
<strong>Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia.</strong>
|
|
Am. J. Hum. Genet. 56: 732-744, 1995.
|
|
|
|
|
|
[PubMed: 7887429]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Modaff, P.
|
|
<strong>Jugular bulb dehiscence in achondroplasia.</strong>
|
|
Int. J. Pediat. Otorhinolaryng. 48: 169-174, 1999.
|
|
|
|
|
|
[PubMed: 10375043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0165-5876(99)00033-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pauli, R. M., Scott, C. I., Wassman, E. R., Jr., Gilbert, E. F., Leavitt, L. A., Ver Hoeve, J., Hall, J. G., Partington, M. W., Jones, K. L., Sommer, A., Feldman, W., Langer, L. O., Rimoin, D. L., Hecht, J. T., Lebovitz, R.
|
|
<strong>Apnea and sudden unexpected death in infants with achondroplasia.</strong>
|
|
J. Pediat. 104: 342-348, 1984.
|
|
|
|
|
|
[PubMed: 6707788]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(84)81092-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Penrose, L. S.
|
|
<strong>Parental age and mutation.</strong>
|
|
Lancet 266: 312-313, 1955. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 13243724]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(55)92305-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Penrose, L. S.
|
|
<strong>Parental age in achondroplasia and mongolism.</strong>
|
|
Am. J. Hum. Genet. 9: 167-169, 1957.
|
|
|
|
|
|
[PubMed: 13507646]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peters, K., Ornitz, D., Werner, S., Williams, L.
|
|
<strong>Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis.</strong>
|
|
Dev. Biol. 155: 423-430, 1993.
|
|
|
|
|
|
[PubMed: 8432397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/dbio.1993.1040]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Philip, N., Auger, M., Mattei, J. F., Giraud, F.
|
|
<strong>Achondroplasia in sibs of normal parents.</strong>
|
|
J. Med. Genet. 25: 857-859, 1988.
|
|
|
|
|
|
[PubMed: 3236371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.25.12.857]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pierre-Kahn, A., Hirsch, J. F., Renier, D., Metzger, J., Maroteaux, P.
|
|
<strong>Hydrocephalus and achondroplasia: a study of 25 observations.</strong>
|
|
Child's Brain 7: 205-219, 1980.
|
|
|
|
|
|
[PubMed: 7438842]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pulst, S.-M., Graham, J. M., Jr., Fain, P., Barker, D., Pribyl, T., Korenberg, J. R.
|
|
<strong>The achondroplasia gene is not linked to the locus for neurofibromatosis 1 on chromosome 17.</strong>
|
|
Hum. Genet. 85: 12-14, 1990.
|
|
|
|
|
|
[PubMed: 2162805]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00276318]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pyeritz, R. E., Sack, G. H., Jr., Udvarhelyi, G. B.
|
|
<strong>Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients.</strong>
|
|
Am. J. Med. Genet. 28: 433-444, 1987.
|
|
|
|
|
|
[PubMed: 3425618]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320280221]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Randolph, L. M., Shohat, M., Miller, D., Lachman, R., Rimoin, D. L.
|
|
<strong>Achondroplasia with ankylosing spondylitis.</strong>
|
|
Am. J. Med. Genet. 31: 117-121, 1988.
|
|
|
|
|
|
[PubMed: 3223492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320310113]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reiser, C. A., Pauli, R. M., Hall, J. G.
|
|
<strong>Achondroplasia: unexpected familial recurrence.</strong>
|
|
Am. J. Med. Genet. 19: 245-250, 1984.
|
|
|
|
|
|
[PubMed: 6507475]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320190206]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reynolds, K. K., Modaff, P., Pauli, R. M.
|
|
<strong>Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia.</strong>
|
|
Am. J. Med. Genet. 101: 40-45, 2001.
|
|
|
|
|
|
[PubMed: 11343336]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1307]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rimoin, D. L., Hughes, G. N., Kaufman, R. L., Rosenthal, R. E., McAlister, W. H., Silberberg, R.
|
|
<strong>Endochondral ossification in achondroplastic dwarfism.</strong>
|
|
New Eng. J. Med. 283: 728-735, 1970.
|
|
|
|
|
|
[PubMed: 4989392]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197010012831404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A.
|
|
<strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong>
|
|
Nature 371: 252-254, 1994.
|
|
|
|
|
|
[PubMed: 8078586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/371252a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J.
|
|
<strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong>
|
|
Am. J. Med. Genet. 140A: 284-290, 2006.
|
|
|
|
|
|
[PubMed: 16411219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31084]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Savarirayan, R., Irving, M., Bacino, C. A., Bostwick, B., Charrow, J., Cormier-Daire, V., Sang, K.-H. L. Q., Dickson, P., Harmatz, P., Phillips, J., Owen, N., Cherukuri, A., Jayaram, K., Jeha, G. S., Larimore, K., Chan, M.-L., Labed, A. H., Day, J., Hoover-Fong, J.
|
|
<strong>C-type natriuretic peptide analogue therapy in children with achondroplasia.</strong>
|
|
New Eng. J. Med. 381: 25-35, 2019.
|
|
|
|
|
|
[PubMed: 31269546]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1813446]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J.
|
|
<strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong>
|
|
Cell 78: 335-342, 1994.
|
|
|
|
|
|
[PubMed: 7913883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90302-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shohat, M., Tick, D., Barakat, S., Bu, X., Melmed, S., Rimoin, D. L.
|
|
<strong>Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia.</strong>
|
|
J. Clin. Endocr. Metab. 81: 4033-4037, 1996.
|
|
|
|
|
|
[PubMed: 8923856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.81.11.8923856]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siebens, A. A., Hungerford, D. S., Kirby, N. A.
|
|
<strong>Curves of the achondroplastic spine: a new hypothesis.</strong>
|
|
Johns Hopkins Med. J. 142: 205-210, 1978.
|
|
|
|
|
|
[PubMed: 149212]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A.
|
|
<strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong>
|
|
J. Med. Genet. 37: 958-959, 2000.
|
|
|
|
|
|
[PubMed: 11186940]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.37.12.958]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sommer, A., Young-Wee, T., Frye, T.
|
|
<strong>Achondroplasia-hypochondroplasia complex.</strong>
|
|
Am. J. Med. Genet. 26: 949-957, 1987.
|
|
|
|
|
|
[PubMed: 3591840]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320260426]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stanescu, R., Stanescu, V., Maroteaux, P.
|
|
<strong>Homozygous achondroplasia: morphologic and biochemical study of cartilage.</strong>
|
|
Am. J. Med. Genet. 37: 412-421, 1990.
|
|
|
|
|
|
[PubMed: 2260574]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320370323]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stoll, C., Dott, B., Roth, M.-P., Alembik, Y.
|
|
<strong>Birth prevalence rates of skeletal dysplasias.</strong>
|
|
Clin. Genet. 35: 88-92, 1989.
|
|
|
|
|
|
[PubMed: 2785882]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1989.tb02912.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stoll, C., Feingold, J.
|
|
<strong>Do parents and grandparents of patients with achondroplasia have a higher cancer risk?</strong>
|
|
Am. J. Med. Genet. 130A: 165-168, 2004.
|
|
|
|
|
|
[PubMed: 15372518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30273]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stoll, C., Roth, M.-P., Bigel, P.
|
|
<strong>A reexamination of parental age effect on the occurrence of new mutations for achondroplasia. In: Papadatos, C. J.; Bartsocas, C. S. (eds.): Skeletal Dysplasias.</strong>
|
|
New York: Alan R. Liss (pub.) 1982. Pp. 419-426.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strom, C. M.
|
|
<strong>Achondroplasia due to DNA insertion into the type II collagen gene. (Abstract)</strong>
|
|
Pediat. Res. 18: 226A, 1984.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B.
|
|
<strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong>
|
|
Europ. J. Pediat. 154: 215-219, 1995.
|
|
|
|
|
|
[PubMed: 7758520]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01954274]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tasker, R. C., Dundas, I., Laverty, A., Fletcher, M., Lane, R., Stocks, J.
|
|
<strong>Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study.</strong>
|
|
Arch. Dis. Child. 79: 99-108, 1998.
|
|
|
|
|
|
[PubMed: 9797588]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.79.2.99]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, J. N., Jr., Schaefer, G. B., Conley, M. C., Mascie-Taylor, C. G. N.
|
|
<strong>Achondroplasia and parental age. (Letter)</strong>
|
|
New Eng. J. Med. 314: 521-522, 1986.
|
|
|
|
|
|
[PubMed: 3945286]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/nejm198602203140820]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tiemann-Boege, I., Navidi, W., Grewal, R., Cohn, D., Eskenazi, B., Wyrobek, A. J., Arnheim, N.
|
|
<strong>The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 14952-14957, 2002.
|
|
|
|
|
|
[PubMed: 12397172]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.232568699]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Fryns, J. P.
|
|
<strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong>
|
|
Genet. Counsel. 15: 375-377, 2004.
|
|
|
|
|
|
[PubMed: 15517832]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Velinov, M., Slaugenhaupt, S. A., Stoilov, I., Scott, C. I., Jr., Gusella, J. F., Tsipouras, P.
|
|
<strong>The gene for achondroplasia maps to the telomeric region of chromosome 4p.</strong>
|
|
Nature Genet. 6: 314-317, 1994.
|
|
|
|
|
|
[PubMed: 8012397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0394-314]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verloes, A., Massart, B., Jossa, V., Langhendries, J. P., Hainaut, H., Paquot, J. P., Koulischer, L.
|
|
<strong>Neuroblastoma in a dwarfed newborn: possible clue to the chromosomal localization of the gene for achondroplasia?</strong>
|
|
Ann. Genet. 34: 25-26, 1991.
|
|
|
|
|
|
[PubMed: 1952787]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wadia, R.
|
|
<strong>Achondroplasia in two first cousins.</strong>
|
|
Birth Defects Orig. Art. Ser. V(4): 227-230, 1969.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wallace, D. C., Exton, L. A., Pritchard, D. A., Leung, Y., Cooke, R. A.
|
|
<strong>Severe achondroplasia: demonstration of probable heterogeneity within this clinical syndrome.</strong>
|
|
J. Med. Genet. 7: 22-26, 1970.
|
|
|
|
|
|
[PubMed: 5480962]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.7.1.22]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waller, D. K., Correa, A., Vo, T. M., Wang, Y., Hobbs, C., Langlois, P. H., Pearson, K., Romitti, P. A., Shaw, G. M., Hecht, J. T.
|
|
<strong>The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.</strong>
|
|
Am. J. Med. Genet. 146A: 2385-2389, 2008.
|
|
|
|
|
|
[PubMed: 18698630]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32485]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waters, K. A., Everett, F., Sillence, D. O., Fagan, E. R., Sullivan, C. E.
|
|
<strong>Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials.</strong>
|
|
Am. J. Med. Genet. 59: 460-466, 1995.
|
|
|
|
|
|
[PubMed: 8585566]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320590412]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weber, G., Prinster, C., Meneghel, M., Russo, F., Mora, S., Puzzovio, M., Del Maschio, M., Chiumello, G.
|
|
<strong>Human growth hormone treatment in prepubertal children with achondroplasia.</strong>
|
|
Am. J. Med. Genet. 61: 396-400, 1996.
|
|
|
|
|
|
[PubMed: 8834055]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960202)61:4<396::AID-AJMG17>3.0.CO;2-N]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weinberg, W.
|
|
<strong>Zur Vererbung des Zwergwuchses.</strong>
|
|
Arch. Rass. Ges. Biol. 9: 710-717, 1912.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Woods, C. G., Rogers, J. G., Mayne, V.
|
|
<strong>Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.</strong>
|
|
J. Med. Genet. 31: 565-569, 1994.
|
|
|
|
|
|
[PubMed: 7966194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.31.7.565]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wynn, J., King, T. M., Gambello, M. J., Waller, D. K., Hecht, J. T.
|
|
<strong>Mortality in achondroplasia study: a 42-year follow-up.</strong>
|
|
Am. J. Med. Genet. 143A: 2502-2511, 2007.
|
|
|
|
|
|
[PubMed: 17879967]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31919]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yang, S. S., Corbett, D. P., Brough, A. J., Heidelberger, K. P., Bernstein, J.
|
|
<strong>Upper cervical myelopathy in achondroplasia.</strong>
|
|
Am. J. Clin. Path. 68: 68-72, 1977.
|
|
|
|
|
|
[PubMed: 868806]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/ajcp/68.1.68]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K.
|
|
<strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong>
|
|
Nature Med. 10: 80-86, 2004.
|
|
|
|
|
|
[PubMed: 14702637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm971]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Young, I. D., Ruggins, N. R., Somers, J. M., Zuccollo, J. M., Rutter, N.
|
|
<strong>Lethal skeletal dysplasia owing to a double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita.</strong>
|
|
J. Med. Genet. 29: 831-833, 1992.
|
|
|
|
|
|
[PubMed: 1453438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.29.11.831]
|
|
|
|
|
|
</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 : 07/09/2019<br>Marla J. F. O'Neill - updated : 10/9/2013<br>Ada Hamosh - updated : 1/8/2013<br>Nara Sobreira - updated : 11/20/2009<br>Nara Sobreira - updated : 5/22/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 12/30/2008<br>Kelly A. Przylepa - updated : 5/5/2008<br>Marla J. F. O'Neill - updated : 4/30/2008<br>Marla J. F. O'Neill - updated : 3/2/2007<br>Marla J. F. O'Neill - updated : 11/10/2006<br>Marla J. F. O'Neill - updated : 3/7/2006<br>Cassandra L. Kniffin - updated : 2/8/2006<br>Victor A. McKusick - updated : 1/18/2006<br>Victor A. McKusick - updated : 1/12/2005<br>Victor A. McKusick - updated : 12/6/2004<br>Victor A. McKusick - updated : 11/23/2004<br>Marla J. F. O'Neill - updated : 6/30/2004<br>Victor A. McKusick - updated : 10/8/2003<br>Victor A. McKusick - updated : 5/16/2001<br>Michael J. Wright - updated : 2/6/2001<br>Armand Bottani - updated : 3/15/2000<br>Victor A. McKusick - updated : 2/24/2000<br>Paul Brennan - updated : 1/27/1999<br>Michael J. Wright - updated : 10/7/1998<br>Victor A. McKusick - updated : 10/9/1997<br>Victor A. McKusick - updated : 5/16/1997<br>John A. Phillips, III - updated : 4/1/1997<br>Victor A. McKusick - updated : 2/4/1997<br>Iosif W. Lurie - updated : 7/1/1996<br>Beat Steinmann - updated : 2/4/1994
|
|
</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 : 6/16/1986
|
|
</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 : 06/06/2024<br>carol : 03/11/2021<br>carol : 07/10/2019<br>alopez : 07/09/2019<br>carol : 11/10/2016<br>carol : 03/02/2015<br>carol : 6/18/2014<br>carol : 10/9/2013<br>alopez : 1/8/2013<br>terry : 1/8/2013<br>terry : 1/13/2011<br>carol : 11/24/2009<br>terry : 11/20/2009<br>carol : 9/21/2009<br>carol : 5/22/2009<br>alopez : 4/16/2009<br>terry : 1/7/2009<br>wwang : 1/7/2009<br>ckniffin : 12/30/2008<br>wwang : 5/9/2008<br>carol : 5/5/2008<br>terry : 4/30/2008<br>wwang : 3/8/2007<br>wwang : 3/6/2007<br>terry : 3/2/2007<br>wwang : 11/13/2006<br>terry : 11/10/2006<br>wwang : 3/16/2006<br>wwang : 3/15/2006<br>terry : 3/7/2006<br>terry : 3/7/2006<br>wwang : 2/13/2006<br>ckniffin : 2/8/2006<br>alopez : 1/20/2006<br>terry : 1/18/2006<br>terry : 2/22/2005<br>terry : 2/18/2005<br>wwang : 1/19/2005<br>wwang : 1/13/2005<br>terry : 1/12/2005<br>alopez : 12/6/2004<br>tkritzer : 11/30/2004<br>terry : 11/23/2004<br>carol : 7/1/2004<br>carol : 7/1/2004<br>terry : 6/30/2004<br>terry : 6/2/2004<br>terry : 2/19/2004<br>terry : 2/19/2004<br>alopez : 11/3/2003<br>alopez : 10/8/2003<br>carol : 12/10/2002<br>tkritzer : 12/6/2002<br>terry : 12/4/2002<br>mcapotos : 5/23/2001<br>mcapotos : 5/22/2001<br>terry : 5/16/2001<br>alopez : 4/9/2001<br>alopez : 2/6/2001<br>carol : 3/15/2000<br>alopez : 2/28/2000<br>terry : 2/24/2000<br>terry : 4/29/1999<br>alopez : 1/27/1999<br>carol : 10/12/1998<br>terry : 10/9/1998<br>terry : 10/7/1998<br>dkim : 9/11/1998<br>terry : 6/3/1998<br>mark : 10/14/1997<br>terry : 10/9/1997<br>alopez : 7/9/1997<br>mark : 7/3/1997<br>mark : 5/16/1997<br>terry : 5/12/1997<br>alopez : 5/12/1997<br>jenny : 4/4/1997<br>jenny : 4/1/1997<br>joanna : 2/14/1997<br>joanna : 2/4/1997<br>terry : 12/17/1996<br>carol : 7/1/1996<br>mark : 4/11/1996<br>mark : 2/26/1996<br>mark : 2/26/1996<br>terry : 2/20/1996<br>mark : 1/17/1996<br>terry : 1/16/1996<br>mark : 7/19/1995<br>terry : 2/27/1995<br>carol : 1/18/1995<br>mimadm : 6/8/1994<br>warfield : 3/31/1994
|
|
</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>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</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>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</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">×</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>
|
|
|
|
|