675 lines
No EOL
160 KiB
HTML
675 lines
No EOL
160 KiB
HTML
<?xml version="1.0" encoding="utf-8"?>
|
||
<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">
|
||
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en">
|
||
|
||
<head><meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
|
||
<!-- AppResources meta begin -->
|
||
<meta name="paf-app-resources" content="" />
|
||
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
||
|
||
<!-- AppResources meta end -->
|
||
|
||
<!-- TemplateResources meta begin -->
|
||
<meta name="paf_template" content="" />
|
||
|
||
<!-- TemplateResources meta end -->
|
||
|
||
<!-- Logger begin -->
|
||
<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK355518" /><meta name="ncbi_domain" content="gene" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK355518/" /><meta name="ncbi_pagename" content="ADNP-Related Disorder - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
||
<!-- Logger end -->
|
||
|
||
<title>ADNP-Related Disorder - GeneReviews® - NCBI Bookshelf</title>
|
||
|
||
<!-- AppResources external_resources begin -->
|
||
<link rel="stylesheet" href="/core/jig/1.15.2/css/jig.min.css" /><script type="text/javascript" src="/core/jig/1.15.2/js/jig.min.js"></script>
|
||
|
||
<!-- AppResources external_resources end -->
|
||
|
||
<!-- Page meta begin -->
|
||
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="ADNP-Related Disorder" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2022/10/06" /><meta name="citation_author" content="Anke Van Dijck" /><meta name="citation_author" content="Geert Vandeweyer" /><meta name="citation_author" content="Frank Kooy" /><meta name="citation_pmid" content="27054228" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK355518/" /><meta name="citation_keywords" content="Helsmoortel-Van der Aa Syndrome" /><meta name="citation_keywords" content="ADNP-Related ID/ASD" /><meta name="citation_keywords" content="ADNP-Related ID/ASD" /><meta name="citation_keywords" content="Helsmoortel-Van der Aa Syndrome" /><meta name="citation_keywords" content="Activity-dependent neuroprotector homeobox protein" /><meta name="citation_keywords" content="ADNP" /><meta name="citation_keywords" content="ADNP-Related Disorder" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="ADNP-Related Disorder" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Anke Van Dijck" /><meta name="DC.Contributor" content="Geert Vandeweyer" /><meta name="DC.Contributor" content="Frank Kooy" /><meta name="DC.Date" content="2022/10/06" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK355518/" /><meta name="description" content="ADNP-related disorder is characterized by hypotonia, severe speech and motor delay, mild-to-severe intellectual disability, and characteristic facial features (prominent forehead, high anterior hairline, wide and depressed nasal bridge, and short nose with full, upturned nasal tip) based on a cohort of 78 individuals. Features of autism spectrum disorder are common (stereotypic behavior, impaired social interaction). Other common findings include additional behavioral problems, sleep disturbance, brain abnormalities, seizures, feeding issues, gastrointestinal problems, visual dysfunction (hypermetropia, strabismus, cortical visual impairment), musculoskeletal anomalies, endocrine issues including short stature and hormonal deficiencies, cardiac and urinary tract anomalies, and hearing loss." /><meta name="og:title" content="ADNP-Related Disorder" /><meta name="og:type" content="book" /><meta name="og:description" content="ADNP-related disorder is characterized by hypotonia, severe speech and motor delay, mild-to-severe intellectual disability, and characteristic facial features (prominent forehead, high anterior hairline, wide and depressed nasal bridge, and short nose with full, upturned nasal tip) based on a cohort of 78 individuals. Features of autism spectrum disorder are common (stereotypic behavior, impaired social interaction). Other common findings include additional behavioral problems, sleep disturbance, brain abnormalities, seizures, feeding issues, gastrointestinal problems, visual dysfunction (hypermetropia, strabismus, cortical visual impairment), musculoskeletal anomalies, endocrine issues including short stature and hormonal deficiencies, cardiac and urinary tract anomalies, and hearing loss." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK355518/" /><meta name="og:site_name" content="NCBI Bookshelf" /><meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" /><meta name="twitter:card" content="summary" /><meta name="twitter:site" content="@ncbibooks" /><meta name="bk-non-canon-loc" content="/books/n/gene/adnp-dis/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK355518/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
|
||
|
||
<!-- Page meta end -->
|
||
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico" /><meta name="ncbi_phid" content="CE8E98FE7D2A12110000000000BB0093.m_13" />
|
||
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3985586/3808861/4121862/3974050/3917732/251717/4216701/14534/45193/4113719/3849091/3984811/3751656/4033350/3840896/3577051/3852958/4008682/4207974/4206132/4062871/12930/3964959/3854974/36029/4128070/9685/3549676/3609192/3609193/3609213/3395586.css" /><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3411343/3882866.css" media="print" /></head>
|
||
<body class="book-part">
|
||
<div class="grid">
|
||
<div class="col twelve_col nomargin shadow">
|
||
<!-- System messages like service outage or JS required; this is handled by the TemplateResources portlet -->
|
||
<div class="sysmessages">
|
||
<noscript>
|
||
<p class="nojs">
|
||
<strong>Warning:</strong>
|
||
The NCBI web site requires JavaScript to function.
|
||
<a href="/guide/browsers/#enablejs" title="Learn how to enable JavaScript" target="_blank">more...</a>
|
||
</p>
|
||
</noscript>
|
||
</div>
|
||
<!--/.sysmessage-->
|
||
<div class="wrap">
|
||
<div class="page">
|
||
<div class="top">
|
||
<div id="universal_header">
|
||
<section class="usa-banner">
|
||
<div class="usa-accordion">
|
||
<header class="usa-banner-header">
|
||
<div class="usa-grid usa-banner-inner">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/favicons/favicon-57.png" alt="U.S. flag" />
|
||
<p>An official website of the United States government</p>
|
||
<button class="non-usa-accordion-button usa-banner-button" aria-expanded="false" aria-controls="gov-banner-top" type="button">
|
||
<span class="usa-banner-button-text">Here's how you know</span>
|
||
</button>
|
||
</div>
|
||
</header>
|
||
<div class="usa-banner-content usa-grid usa-accordion-content" id="gov-banner-top" aria-hidden="true">
|
||
<div class="usa-banner-guidance-gov usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-dot-gov.svg" alt="Dot gov" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The .gov means it's official.</strong>
|
||
<br />
|
||
Federal government websites often end in .gov or .mil. Before
|
||
sharing sensitive information, make sure you're on a federal
|
||
government site.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
<div class="usa-banner-guidance-ssl usa-width-one-half">
|
||
<img class="usa-banner-icon usa-media_block-img" src="https://www.ncbi.nlm.nih.gov/coreutils/uswds/img/icon-https.svg" alt="Https" />
|
||
<div class="usa-media_block-body">
|
||
<p>
|
||
<strong>The site is secure.</strong>
|
||
<br />
|
||
The <strong>https://</strong> ensures that you are connecting to the
|
||
official website and that any information you provide is encrypted
|
||
and transmitted securely.
|
||
</p>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<div class="usa-overlay"></div>
|
||
<header class="ncbi-header" role="banner" data-section="Header">
|
||
|
||
<div class="usa-grid">
|
||
<div class="usa-width-one-whole">
|
||
|
||
<div class="ncbi-header__logo">
|
||
<a href="/" class="logo" aria-label="NCBI Logo" data-ga-action="click_image" data-ga-label="NIH NLM Logo">
|
||
<img src="https://www.ncbi.nlm.nih.gov/coreutils/nwds/img/logos/AgencyLogo.svg" alt="NIH NLM Logo" />
|
||
</a>
|
||
</div>
|
||
|
||
<div class="ncbi-header__account">
|
||
<a id="account_login" href="https://account.ncbi.nlm.nih.gov" class="usa-button header-button" style="display:none" data-ga-action="open_menu" data-ga-label="account_menu">Log in</a>
|
||
<button id="account_info" class="header-button" style="display:none" aria-controls="account_popup" type="button">
|
||
<span class="fa fa-user" aria-hidden="true">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 24 24" width="20px" height="20px">
|
||
<g style="fill: #fff">
|
||
<ellipse cx="12" cy="8" rx="5" ry="6"></ellipse>
|
||
<path d="M21.8,19.1c-0.9-1.8-2.6-3.3-4.8-4.2c-0.6-0.2-1.3-0.2-1.8,0.1c-1,0.6-2,0.9-3.2,0.9s-2.2-0.3-3.2-0.9 C8.3,14.8,7.6,14.7,7,15c-2.2,0.9-3.9,2.4-4.8,4.2C1.5,20.5,2.6,22,4.1,22h15.8C21.4,22,22.5,20.5,21.8,19.1z"></path>
|
||
</g>
|
||
</svg>
|
||
</span>
|
||
<span class="username desktop-only" aria-hidden="true" id="uname_short"></span>
|
||
<span class="sr-only">Show account info</span>
|
||
</button>
|
||
</div>
|
||
|
||
<div class="ncbi-popup-anchor">
|
||
<div class="ncbi-popup account-popup" id="account_popup" aria-hidden="true">
|
||
<div class="ncbi-popup-head">
|
||
<button class="ncbi-close-button" data-ga-action="close_menu" data-ga-label="account_menu" type="button">
|
||
<span class="fa fa-times">
|
||
<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 48 48" width="24px" height="24px">
|
||
<path d="M38 12.83l-2.83-2.83-11.17 11.17-11.17-11.17-2.83 2.83 11.17 11.17-11.17 11.17 2.83 2.83 11.17-11.17 11.17 11.17 2.83-2.83-11.17-11.17z"></path>
|
||
</svg>
|
||
</span>
|
||
<span class="usa-sr-only">Close</span></button>
|
||
<h4>Account</h4>
|
||
</div>
|
||
<div class="account-user-info">
|
||
Logged in as:<br />
|
||
<b><span class="username" id="uname_long">username</span></b>
|
||
</div>
|
||
<div class="account-links">
|
||
<ul class="usa-unstyled-list">
|
||
<li><a id="account_myncbi" href="/myncbi/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_myncbi">Dashboard</a></li>
|
||
<li><a id="account_pubs" href="/myncbi/collections/bibliography/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_pubs">Publications</a></li>
|
||
<li><a id="account_settings" href="/account/settings/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_settings">Account settings</a></li>
|
||
<li><a id="account_logout" href="/account/signout/" class="set-base-url" data-ga-action="click_menu_item" data-ga-label="account_logout">Log out</a></li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</header>
|
||
<div role="navigation" aria-label="access keys">
|
||
<a id="nws_header_accesskey_0" href="https://www.ncbi.nlm.nih.gov/guide/browsers/#ncbi_accesskeys" class="usa-sr-only" accesskey="0" tabindex="-1">Access keys</a>
|
||
<a id="nws_header_accesskey_1" href="https://www.ncbi.nlm.nih.gov" class="usa-sr-only" accesskey="1" tabindex="-1">NCBI Homepage</a>
|
||
<a id="nws_header_accesskey_2" href="/myncbi/" class="set-base-url usa-sr-only" accesskey="2" tabindex="-1">MyNCBI Homepage</a>
|
||
<a id="nws_header_accesskey_3" href="#maincontent" class="usa-sr-only" accesskey="3" tabindex="-1">Main Content</a>
|
||
<a id="nws_header_accesskey_4" href="#" class="usa-sr-only" accesskey="4" tabindex="-1">Main Navigation</a>
|
||
</div>
|
||
<section data-section="Alerts">
|
||
<div class="ncbi-alerts-placeholder"></div>
|
||
</section>
|
||
</div>
|
||
<div class="header">
|
||
<div class="res_logo"><h1 class="res_name"><a href="/books/" title="Bookshelf home">Bookshelf</a></h1><h2 class="res_tagline"></h2></div>
|
||
<div class="search"><form method="get" action="/books/"><div class="search_form"><label for="database" class="offscreen_noflow">Search database</label><select id="database"><optgroup label="Recent"><option value="books" selected="selected" data-ac_dict="bookshelf-search">Books</option><option value="pubmed">PubMed</option><option value="clinvar">ClinVar</option><option value="medgen" class="last">MedGen</option></optgroup><optgroup label="All"><option value="gquery">All Databases</option><option value="assembly">Assembly</option><option value="biocollections">Biocollections</option><option value="bioproject">BioProject</option><option value="biosample">BioSample</option><option value="books" data-ac_dict="bookshelf-search">Books</option><option value="clinvar">ClinVar</option><option value="cdd">Conserved Domains</option><option value="gap">dbGaP</option><option value="dbvar">dbVar</option><option value="gene">Gene</option><option value="genome">Genome</option><option value="gds">GEO DataSets</option><option value="geoprofiles">GEO Profiles</option><option value="gtr">GTR</option><option value="ipg">Identical Protein Groups</option><option value="medgen">MedGen</option><option value="mesh">MeSH</option><option value="nlmcatalog">NLM Catalog</option><option value="nuccore">Nucleotide</option><option value="omim">OMIM</option><option value="pmc">PMC</option><option value="protein">Protein</option><option value="proteinclusters">Protein Clusters</option><option value="protfam">Protein Family Models</option><option value="pcassay">PubChem BioAssay</option><option value="pccompound">PubChem Compound</option><option value="pcsubstance">PubChem Substance</option><option value="pubmed">PubMed</option><option value="snp">SNP</option><option value="sra">SRA</option><option value="structure">Structure</option><option value="taxonomy">Taxonomy</option><option value="toolkit">ToolKit</option><option value="toolkitall">ToolKitAll</option><option value="toolkitbookgh">ToolKitBookgh</option></optgroup></select><div class="nowrap"><label for="term" class="offscreen_noflow" accesskey="/">Search term</label><div class="nowrap"><input type="text" name="term" id="term" title="Search Books. Use up and down arrows to choose an item from the autocomplete." value="" class="jig-ncbiclearbutton jig-ncbiautocomplete" data-jigconfig="dictionary:'bookshelf-search',disableUrl:'NcbiSearchBarAutoComplCtrl'" autocomplete="off" data-sbconfig="ds:'no',pjs:'no',afs:'no'" /></div><button id="search" type="submit" class="button_search nowrap" cmd="go">Search</button></div></div></form><ul class="searchlinks inline_list"><li>
|
||
<a href="/books/browse/">Browse Titles</a>
|
||
</li><li>
|
||
<a href="/books/advanced/">Advanced</a>
|
||
</li><li class="help">
|
||
<a href="/books/NBK3833/">Help</a>
|
||
</li><li class="disclaimer">
|
||
<a target="_blank" data-ga-category="literature_resources" data-ga-action="link_click" data-ga-label="disclaimer_link" href="https://www.ncbi.nlm.nih.gov/books/about/disclaimer/">Disclaimer</a>
|
||
</li></ul></div>
|
||
</div>
|
||
|
||
|
||
|
||
<!--<component id="Page" label="headcontent"/>-->
|
||
|
||
</div>
|
||
<div class="content">
|
||
<!-- site messages -->
|
||
<!-- Custom content 1 -->
|
||
<div class="col1">
|
||
|
||
</div>
|
||
|
||
<div class="container">
|
||
<div id="maincontent" class="content eight_col col">
|
||
<!-- Custom content in the left column above book nav -->
|
||
<div class="col2">
|
||
|
||
</div>
|
||
|
||
<!-- Book content -->
|
||
|
||
|
||
<!-- Custom content between navigation and content -->
|
||
<div class="col3">
|
||
|
||
</div>
|
||
|
||
<div class="document">
|
||
<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK355518_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK355518_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/adcy5-dysk/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/ipa/" title="Next page in this title">Next ></a></div></div></div></div></div>
|
||
<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK355518_"><span class="title" itemprop="name"><i>ADNP-</i>Related Disorder</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Helsmoortel-Van der Aa Syndrome, <i>ADNP</i>-Related ID/ASD</div><p class="contrib-group"><span itemprop="author">Anke Van Dijck</span>, MD, PhD, <span itemprop="author">Geert Vandeweyer</span>, PhD, and <span itemprop="author">Frank Kooy</span>, PhD.</p><a data-jig="ncbitoggler" href="#__NBK355518_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK355518_ai__"><div class="contrib half_rhythm"><span itemprop="author">Anke Van Dijck</span>, MD, PhD<div class="affiliation small">Neurologist, Rehabilitation Department<br />De Mick, Klina Hospital Brasschaat<br />Brasschaat, Belgium</div><div class="affiliation small">Postdoctoral Research Assistant, University of Antwerp<br />Edegem, Belgium<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.neprewtnau@kcjidnav.ekna" class="oemail">eb.neprewtnau@kcjidnav.ekna</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Geert Vandeweyer</span>, PhD<div class="affiliation small">Laboratory Coordinator, Bioinformatics<br />Antwerp University Hospital<br />Edegem, Belgium<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.azu@reyewednav.treeg" class="oemail">eb.azu@reyewednav.treeg</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Frank Kooy</span>, PhD<div class="affiliation small">Professor, Cognitive Genetics<br />Department of Medical Genetics<br />University of Antwerp<br />Edegem, Belgium<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="eb.neprewtnau@yook.knarf" class="oemail">eb.neprewtnau@yook.knarf</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">April 7, 2016</span>; Last Revision: <span itemprop="dateModified">October 6, 2022</span>.</p><p><em>Estimated reading time: 19 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="adnp-dis.Summary" itemprop="description"><h2 id="_adnp-dis_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>ADNP</i>-related disorder is characterized by hypotonia, severe speech and motor delay, mild-to-severe intellectual disability, and characteristic facial features (prominent forehead, high anterior hairline, wide and depressed nasal bridge, and short nose with full, upturned nasal tip) based on a cohort of 78 individuals. Features of autism spectrum disorder are common (stereotypic behavior, impaired social interaction). Other common findings include additional behavioral problems, sleep disturbance, brain abnormalities, seizures, feeding issues, gastrointestinal problems, visual dysfunction (hypermetropia, strabismus, cortical visual impairment), musculoskeletal anomalies, endocrine issues including short stature and hormonal deficiencies, cardiac and urinary tract anomalies, and hearing loss.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>ADNP</i>-related disorder is established by identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> on <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment is symptomatic and can include: speech, occupational, and physical therapy; specialized learning programs depending on individual needs; treatment of neuropsychiatric features; nutritional support as needed; standard treatment of gastrointestinal, ophthalmologic, musculoskeletal, endocrine, and cardiac findings; standard treatments for hearing loss, seizures, urinary tract anomalies, and recurrent infections.</p><p><i>Surveillance:</i> At each visit monitor growth and nutrition, occupational and physical therapy needs; assess for seizures, developmental progress, behavioral issues, gastrointestinal issues, and family needs; annual vision assessment.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>ADNP</i>-related disorder is expressed in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner and typically caused by a <i>de novo ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the risk to other family members is presumed to be low. Once an <i>ADNP</i> pathogenic variant has been identified in an affected family member, <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a> and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="adnp-dis.Diagnosis"><h2 id="_adnp-dis_Diagnosis_">Diagnosis</h2><div id="adnp-dis.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>ADNP</i>-related disorder <b>should be considered</b> in individuals with the following clinical and MRI findings.</p><p>
|
||
<b>Clinical findings</b>
|
||
</p><ul><li class="half_rhythm"><div>Severe speech and motor delay</div></li><li class="half_rhythm"><div>Mild-to-severe intellectual disability</div></li><li class="half_rhythm"><div>Autism spectrum disorder, additional behavioral problems, and sleep disturbance</div></li><li class="half_rhythm"><div>Characteristic facial appearance including prominent forehead, high anterior hairline, downslanted palpebral fissures, prominent eyelashes, ear malformations, wide and depressed nasal bridge, short nose with full, upturned nasal tip, long philtrum, thin vermilion of the upper lip, pointed chin, and widely spaced teeth. See <a class="figpopup" href="/books/NBK355518/figure/adnp-dis.F1/?report=objectonly" target="object" rid-figpopup="figadnpdisF1" rid-ob="figobadnpdisF1">Figure 1</a>.</div></li><li class="half_rhythm"><div>Feeding difficulties and gastrointestinal problems (e.g., gastroesophageal reflux disease, lack of satiation, frequent vomiting, constipation)</div></li><li class="half_rhythm"><div>Vison issues (e.g., strabismus, cortical visual impairment, hypermetropia) and various ophthalmologic defects</div></li><li class="half_rhythm"><div>Musculoskeletal anomalies (e.g., joint laxity, hand and foot anomalies, pectus deformities, plagiocephaly)</div></li><li class="half_rhythm"><div>Other features: endocrine manifestations, cardiac and renal anomalies, hearing loss, seizures, recurrent infections</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figadnpdisF1" co-legend-rid="figlgndadnpdisF1"><a href="/books/NBK355518/figure/adnp-dis.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figadnpdisF1" rid-ob="figobadnpdisF1"><img class="small-thumb" src="/books/NBK355518/bin/adnp-dis-Image001.gif" src-large="/books/NBK355518/bin/adnp-dis-Image001.jpg" alt="Figure 1. . Facial features of individuals with ADNP pathogenic variants." /></a><div class="icnblk_cntnt" id="figlgndadnpdisF1"><h4 id="adnp-dis.F1"><a href="/books/NBK355518/figure/adnp-dis.F1/?report=objectonly" target="object" rid-ob="figobadnpdisF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Facial features of individuals with <i>ADNP</i> pathogenic variants. Frontal and lateral views. Note the prominent forehead with high anterior hairline, the wide and depressed nasal bridge, and short nose with full, upturned nasal tip [Van Dijck et al 2019]. <a href="/books/NBK355518/figure/adnp-dis.F1/?report=objectonly" target="object" rid-ob="figobadnpdisF1">(more...)</a></p></div></div><p><b>MRI findings</b> include atypical white matter lesions, wide ventricles, corpus callosum underdevelopment, cerebral atrophy, cortical dysplasia, and choroid cysts. Note that these findings are not sufficiently distinct to specifically suggest the diagnosis of <i>ADNP</i>-related disorder.</p></div><div id="adnp-dis.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>ADNP</i>-related disorder <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive findings and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>ADNP</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK355518/table/adnp-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobadnpdisTmoleculargenetictestinguse">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bk_pop" href="#adnp-dis.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>ADNP</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out the diagnosis.</p><p><b>Molecular genetic testing</b> in a child with developmental delay or an older individual with intellectual disability typically begins with <a class="def" href="/books/n/gene/glossary/def-item/chromosomal-microarray/">chromosomal microarray</a> analysis (CMA). If CMA is not diagnostic, the next step is typically either a <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a> or <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>. Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing (<a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> of <i>ADNP</i>, followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>) may be indicated in individuals with the distinctive findings described in <a href="#adnp-dis.Suggestive_Findings">Suggestive Findings</a>.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Chromosomal microarray analysis (CMA)</b> uses oligonucleotide or <a class="def" href="/books/n/gene/glossary/def-item/snp-array/">SNP array</a> to detect genome-wide large deletions/duplications (including <i>ADNP</i>) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>ADNP</i> can be performed to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>ADNP</i> and other genes of interest (see <a href="#adnp-dis.Differential_Diagnosis">Differential Diagnosis</a>) may be considered to identify the genetic cause while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i> (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved. <b>Exome sequencing</b> is most commonly used and yields results similar to a <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a> with the additional advantage that <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> includes genes recently identified as causing intellectual disability whereas some multigene panels may not. <b>Genome sequencing</b> is also possible.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Epigenetic signature analysis / <a class="def" href="/books/n/gene/glossary/def-item/methylation/">methylation</a> array.</b> Two distinctive <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> signatures (disorder-specific genome-wide changes in DNA methylation profiles) in peripheral blood leukocytes have been identified in individuals with <i>ADNP</i>-related disorder [<a class="bk_pop" href="#adnp-dis.REF.arefeshghi.2020.356">Aref-Eshghi et al 2020</a>]. Individuals with an <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> located outside the region between nucleotides 2000 and 2340 have a distinct epigenetic signature, whereas individuals with an <i>ADNP</i> pathogenic variant located between nucleotides 2000 and 2340 have a different epigenetic signature [<a class="bk_pop" href="#adnp-dis.REF.bend.2019.64">Bend et al 2019</a>, <a class="bk_pop" href="#adnp-dis.REF.breen.2020.555">Breen et al 2020</a>]. Epigenetic signature analysis of a peripheral blood sample or DNA banked from a blood sample can therefore be considered to clarify the diagnosis in individuals with clinical findings of <i>ADNP</i>-related disorder and a variant of uncertain clinical significance identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>. For an introduction to epigenetic signature analysis click <a href="/books/n/gene/epigenetics/">here</a>.</div></li></ul><div id="adnp-dis.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>ADNP</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ADNP</i>
|
||
</td><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">99% <sup>4</sup></td></tr><tr><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported</td></tr><tr><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">CMA <sup>6</sup></td><td headers="hd_h_adnp-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1 individual <sup>7</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="adnp-dis.TF.1.1"><p class="no_margin">See <a href="/books/NBK355518/#adnp-dis.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="adnp-dis.TF.1.2"><p class="no_margin">See <a href="#adnp-dis.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>3. </dt><dd><div id="adnp-dis.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="adnp-dis.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#adnp-dis.REF.coe.2014.1063">Coe et al [2014]</a>, <a class="bk_pop" href="#adnp-dis.REF.de_rubeis.2014.209">De Rubeis et al [2014]</a>, <a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al [2014]</a>, <a class="bk_pop" href="#adnp-dis.REF.pescosolido.2014.587">Pescosolido et al [2014]</a>, <a class="bk_pop" href="#adnp-dis.REF.vandeweyer.2014.315">Vandeweyer et al [2014]</a>, <a class="bk_pop" href="#adnp-dis.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group [2015]</a>, and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bk_pop" href="#adnp-dis.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd><dt>5. </dt><dd><div id="adnp-dis.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>6. </dt><dd><div id="adnp-dis.TF.1.6"><p class="no_margin">Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including ADNP) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>. The ability to determine the size of the <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a>/<a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> depends on the type of microarray used and the density of probes in the 20q13.13 region. CMA designs in current clinical use target the 20q13.13 region.</p></div></dd><dt>7. </dt><dd><div id="adnp-dis.TF.1.7"><p class="no_margin">One individual with a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> 20q13.13 <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> that encompassed <i>ADNP</i> and <i>DPM1</i> presented with features consistent with <i>ADNP</i>-related disorder [<a class="bk_pop" href="#adnp-dis.REF.huynh.2018.1497">Huynh et al 2018</a>].</p></div></dd></dl></div></div></div></div></div><div id="adnp-dis.Clinical_Characteristics"><h2 id="_adnp-dis_Clinical_Characteristics_">Clinical Characteristics</h2><div id="adnp-dis.Clinical_Description"><h3>Clinical Description</h3><p>The following clinical description is based on a published report of a large cohort of 78 individuals in whom a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>ADNP</i> has been identified [<a class="bk_pop" href="#adnp-dis.REF.van_dijck.2019.287">Van Dijck et al 2019</a>].</p><p>Of note, the oldest individual known to the authors to date is age 40 years [Author, personal observation].</p><div id="adnp-dis.T.select_features_of_adnprelate" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of <i>ADNP</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.select_features_of_adnprelate/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.select_features_of_adnprelate_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD/ID</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild (in 12%), moderate (36%), or severe (52%) ID; ASD & other behavior disorders are common.</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Characteristic facial features</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prominent forehead, high anterior hairline, downslanted palpebral fissures, prominent eyelashes, ear malformations, wide & depressed nasal bridge, short nose w/full, upturned nasal tip, long philtrum, thin upper lip, pointed chin, widely spaced teeth</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastrointestinal/<br />feeding issues</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">83%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroesophageal reflux disease, constipation, oral movement problems, lack of satiation, swallowing problems, frequent vomiting</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Vision issues</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">74%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Strabismus, cortical visual impairment, hypermetropia, ptosis, nystagmus, myopia</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hand & foot abnormalities</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">62%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Digit abnormalities, single palmar crease, nail anomalies, sandal gap</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Musculoskeletal features</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">55%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Joint hypermobility, scoliosis, hip problems, pectus deformities, skull deformities</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrine issues</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early puberty, thyroid hormone problems, growth hormone deficiency</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><‒2 SD</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Truncal obesity</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital heart anomalies</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">38%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Atrial septal defect, patent ductus arteriosus, mitral valve prolapse, patent foramen ovale, ventricular septal defect</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hearing loss</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">32%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Narrow auditory canal, frequent otitis media, hearing loss</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizures</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">16%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absence seizures, focal seizures w/reduced awareness, epilepsy w/continuous spike & waves during slow-wave sleep</td></tr><tr><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Urinary tract anomalies</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">13%</td><td headers="hd_h_adnp-dis.T.select_features_of_adnprelate_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Narrow ureters, bilateral vesicoureteral reflux</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASD = autism spectrum disorder; DD = developmental delay; ID = intellectual disability</p></div></dd></dl></div></div></div><p><b>Development.</b> Infants often have hypotonia. Developmental milestones are delayed: the average age to sit independently is 13 months, and the average walking age is 2.5 years. Speech impairment is prominent, with expressive language ranging from no words to sentences. Bladder training is delayed in half of affected individuals.</p><p>All have mild-to-severe intellectual disability.</p><p>Autism spectrum disorder (ASD), characterized by stereotypic behavior and impaired social interaction, is reported in 67% of the children. Children have a strong sensory interest (sensory processing disorder). A high pain threshold is common.</p><p><b>Additional behavior problems</b> may include anxiety, obsessive compulsive disorder, aggressive behavior, temper tantrums, attention-deficient/hyperactivity disorder, and sleep problems.</p><p><b>Characteristic facial features</b> include a prominent forehead, high anterior hairline, ptosis, downslanted palpebral fissures, prominent eyelashes, wide and depressed nasal bridge, short nose with full, upturned nasal tip, a long philtrum, thin vermilion of the upper lip, widely spaced teeth, pointed chin, and ear abnormalities including small low-set ears and protruding cup-shaped ears.</p><p><b>Gastrointestinal/feeding.</b> Feeding difficulties and gastrointestinal problems are common, including decreased sucking or chewing, gastroesophageal reflux disease, lack of satiation, frequent vomiting, and constipation. Some individuals required a gastrostomy tube.</p><p><b>Vision issues.</b> More than half have visual problems, most commonly hypermetropia or strabismus. Forty-one percent have cortical visual impairment. Ophthalmologic defects are diverse: ectropion, coloboma, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cataracts, nystagmus, everted or notched eyelid, or mild ptosis.</p><p><b>Hand abnormalities</b> are present, including clinodactyly, polydactyly, small fifth fingers, fetal fingertip pads, prominent interphalangeal joints and distal phalanges, a single palmar crease, and nail anomalies.</p><p><b>Foot abnormalities</b> include toe malformations, flat feet, and sandal gap.</p><p><b>Additional muscular skeletal features</b> include joint laxity (38%), pectus deformities (22%) such as pectus excavatum, pectus carinatum or narrow thorax, or skull deformity (14%) including plagiocephaly, trigonocephaly, or brachycephaly.</p><p><b>Endocrine</b> manifestations include thyroid hormone problems (15%, mainly hypothyroidism) and/or growth hormone deficiency. Some have signs of early pubertal development.</p><p><b>Growth.</b> Birth weight, length, and occipitofrontal circumference are within the normal range. Several develop truncal obesity. Twenty-three percent of the individuals have short stature (height <-2 SD in individuals reported with age range of 2-23 years). Growth hormone deficiency is present in 11%.</p><p><b>Cardiac anomalies.</b> Atrial septal defect is the most common. Less frequent cardiac defects include: patent ductus arteriosus, patent foramen ovale, mitral valve prolapse, ventricular septal defect, and other cardiovascular malformations.</p><p><b>Seizures.</b> Some children have seizures (16%) including absence seizures, focal seizures with reduced awareness, and epilepsy with continuous spike and waves during slow-wave sleep.</p><p><b>Renal.</b> Renal anomalies include narrow ureters or bilateral vesicoureteral reflux.</p><p><b>Recurrent infections.</b> Most children have recurrent infections, including upper respiratory and urinary tract infections (51%).</p><p>
|
||
<b>Other</b>
|
||
</p><ul><li class="half_rhythm"><div>Submucous cleft palate (1 individual)</div></li><li class="half_rhythm"><div>Metopic craniosynostosis (2 individuals)</div></li></ul></div><div id="adnp-dis.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>There is no evidence for a clinically relevant impact of a specific <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> on the clinical presentation. However, it was noticed that individuals with a <a href="/books/NBK355518/table/adnp-dis.T.notable_adnp_pathogenic_varia/?report=objectonly" target="object" rid-ob="figobadnpdisTnotableadnppathogenicvaria">p.Tyr719Ter</a> pathogenic variant walked later and had a higher pain threshold than those with other <i>ADNP</i> pathogenic variants [<a class="bk_pop" href="#adnp-dis.REF.van_dijck.2019.287">Van Dijck et al 2019</a>].</p></div><div id="adnp-dis.Penetrance"><h3>Penetrance</h3><p>Penetrance is less than 100%; In two families reported to date, probands diagnosed with <i>ADNP</i>-related disorder inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from an unaffected parent [<a class="bk_pop" href="#adnp-dis.REF.van_dijck.2019.287">Van Dijck et al 2019</a>].</p></div><div id="adnp-dis.Prevalence"><h3>Prevalence</h3><p>The prevalence of pathogenic variants in <i>ADNP</i> is estimated at 0.17% of individuals with ASD (95% binomial confidence interval: 0.083%-0.32%). It is one of the most common known single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> causes of ASD [<a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al 2014</a>].</p></div></div><div id="adnp-dis.Genetically_Related_Allelic_Dis"><h2 id="_adnp-dis_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>ADNP</i>.</p></div><div id="adnp-dis.Differential_Diagnosis"><h2 id="_adnp-dis_Differential_Diagnosis_">Differential Diagnosis</h2><p>Phenotypic features associated with <i>ADNP</i> pathogenic variants are not sufficient to diagnose <i>ADNP</i>-related disorder. All genes known to be associated with intellectual disability * should be included in the differential diagnosis of <i>ADNP</i>-related disorder.</p><p>* More than 200 have been identified; see <a href="https://www.omim.org/phenotypicSeries/PS156200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM Autosomal Dominant</a>, <a href="https://omim.org/phenotypicSeries/PS249500" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Autosomal Recessive</a>, <a href="https://omim.org/phenotypicSeries/PS309530" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Nonsyndromic X-Linked</a>, and <a href="https://omim.org/phenotypicSeries/PS309510" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Syndromic X-Linked Intellectual Developmental Disorder Phenotypic Series</a>.</p></div><div id="adnp-dis.Management"><h2 id="_adnp-dis_Management_">Management</h2><div id="adnp-dis.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>ADNP</i>-related disorder, the evaluations summarized in <a href="/books/NBK355518/table/adnp-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobadnpdisTrecommendedevaluationsfollo">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="adnp-dis.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>ADNP</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comprehensive developmental assessment</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl: motor, adaptive, cognitive, & speech/language eval; testing for ASD & ID; eval for early intervention / special education</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Psychiatric/</b>
|
||
<br />
|
||
<b>Behavioral</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval if behavioral problems are present</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For persons age >12 mos: screen for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD.</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/</b>
|
||
<br />
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of aspiration risk & nutritional status</div></li><li class="half_rhythm"><div>Consider eval for gastric tube placement in those w/dysphagia &/or aspiration risk.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vision</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic exam & vision assessment</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl electrophysiologic & visual perception exam to detect cortical visual impairment</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
|
||
<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Joint hypermobility</div></li><li class="half_rhythm"><div>Mobility, activities of daily living, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of growth parameters</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for growth deficiency, short stature, obesity</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for:
|
||
<ul><li class="half_rhythm"><div>Thyroid problems;</div></li><li class="half_rhythm"><div>Growth hormone deficiency in those w/short stature.</div></li></ul>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiology eval; referral to ENT if indicated</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic exam</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Consider EEG if seizures a concern.</div></li><li class="half_rhythm"><div>To incl brain MRI to detect brain abnormalities</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Urinary tract</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for frequent urinary tract infections</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immunology</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for recurrent infections</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>ADNP-</i>related disorder in order to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#adnp-dis.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; ENT = ear, nose, and throat specialist; ID = intellectual disability; MOI= <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; OT = occupational therapy; PT = physical therapy.</p></div></dd><dt>1. </dt><dd><div id="adnp-dis.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></div></div></div></div><div id="adnp-dis.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Treatment is symptomatic; no specific therapy is available. Routine medical care by a pediatrician or primary care physician is recommended.</p><div id="adnp-dis.T.treatment_of_manifestations_i" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>ADNP</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.treatment_of_manifestations_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.treatment_of_manifestations_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Speech, OT, PT; specialized learning programs depending on individual needs</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Psychiatric/</b>
|
||
<br />
|
||
<b>Behavioral</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment of any neuropsychiatric features incl sleep disorders, &/or behavioral problems</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Poor weight gain /</b>
|
||
<br />
|
||
<b>Failure to thrive</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nutritional support if needed</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment for constipation & gastrointestinal reflux</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Abnormal vision &/or</b>
|
||
<br />
|
||
<b>strabismus</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by ophthalmologist</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Community vision services through early intervention or school district</td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Central visual impairment</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No specific treatment; early intervention to stimulate visual development</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Plagiocephaly / Other</b>
|
||
<br />
|
||
<b>musculoskeletal issues</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypothyroidism</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac anomalies</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment(s) as recommended by cardiologist</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hearing loss</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatments</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Urinary tract anomalies</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Recurrent infections</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
|
||
</td><td headers="hd_h_adnp-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or Special Olympics.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="adnp-dis.TF.4.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div></div><div id="adnp-dis.Surveillance"><h3>Surveillance</h3><div id="adnp-dis.T.recommended_surveillance_for" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>ADNP</i>-Related Disorder</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.recommended_surveillance_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.recommended_surveillance_for_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measurement of growth parameters</div></li><li class="half_rhythm"><div>Eval of nutritional status & safety of oral intake</div></li></ul>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_3" rowspan="5" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical medicine, OT/PT assessment of mobility, self-help skills</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor those w/seizures as clinically indicated.</div></li><li class="half_rhythm"><div>Assess for new manifestations (e.g., seizures, changes in tone, movement disorders).</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Psychiatric/Behavioral</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavioral assessment for anxiety, attention, & aggressive or self-injurious behavior</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Visual assessment</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for constipation & signs/symptoms of gastrointestinal reflux.</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_adnp-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">OT = occupational therapy; PT = physical therapy</p></div></dd></dl></div></div></div></div><div id="adnp-dis.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#adnp-dis.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="adnp-dis.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Administration of NAP, a neuroprotective octapeptide (NAPVSPIQ), has been reported to ameliorate some of the cognitive abnormalities observed in a knockout mouse model [<a class="bk_pop" href="#adnp-dis.REF.bassan.1999.1283">Bassan et al 1999</a>, <a class="bk_pop" href="#adnp-dis.REF.vulihshultzman.2007.438">Vulih-Shultzman et al 2007</a>]. It restores learning and memory and reduces neurodegeneration in <i>Adnp</i><sup>+/−</sup> mice. The drug name for NAP is davunetide, a candidate for treatment of multiple selected neurologic disorders. Intranasal and intravenous formulations of the drug have been shown to cross the blood-brain barrier. Phase II and Phase III clinical trials showed good tolerance without significant side effects. Although it is not known whether the disease is the result of a loss of function of <i>ADNP</i> and although the knockout mouse model has not been evaluated for autistic traits, the observations raise hope for treatment in individuals with <i>ADNP</i>-related disorder [<a class="bk_pop" href="#adnp-dis.REF.vandeweyer.2014.315">Vandeweyer et al 2014</a>].</p><p>A Phase II trial with the drug ketamine in children with <i>ADNP</i>-related disorder is currently recruiting.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="adnp-dis.Genetic_Counseling"><h2 id="_adnp-dis_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="adnp-dis.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>ADNP</i>-related disorder is an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> disorder typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</p></div><div id="adnp-dis.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Most probands reported to date with <i>ADNP</i>-related disorder whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have the disorder as the result of a <i>de novo ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>In two families reported to date, probands diagnosed with <i>ADNP</i>-related disorder inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from an unaffected parent [<a class="bk_pop" href="#adnp-dis.REF.van_dijck.2019.287">Van Dijck et al 2019</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> to confirm their genetic status and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> counseling.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bk_pop" href="#adnp-dis.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from a parent with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (or somatic and germline) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>. Note: Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a>.</div></li></ul></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If the <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> found in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#adnp-dis.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is known to have the <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs of inheriting the variant is 50%.</div></li></ul><p>
|
||
<b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Each child of an individual with <i>ADNP</i>-related disorder has a 50% chance of inheriting the <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Individuals with <i>ADNP</i>-related <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> autism are not known to reproduce.</div></li></ul><p>
|
||
<b>Other family members</b>
|
||
</p><ul><li class="half_rhythm"><div>The risk to other family members depends on the genetic status of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents: if a parent has the <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the parent's family members may be at risk.</div></li><li class="half_rhythm"><div>Given that most probands with <i>ADNP</i>-related disorder reported to date have the disorder as a result of a <i>de novo ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, the risk to other family members is presumed to be low.</div></li></ul></div><div id="adnp-dis.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to the parents of an affected individual.</div></li></ul></div><div id="adnp-dis.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="adnp-dis.Resources"><h2 id="_adnp-dis_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>ADNP Kids Research Foundation</b>
|
||
</div><div>
|
||
<a href="http://www.adnpfoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">adnpfoundation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>ADNP Kids-HVDAS Belgium</b>
|
||
</div><div>Belgium</div><div><b>Email:</b> adnpkids.hvdasbelgium@gmail.com</div><div>
|
||
<a href="https://www.trefpuntstan.be/adnp-kids" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">trefpuntstan.be/adnp-kids</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Amis de ADNP France</b>
|
||
</div><div>France</div><div><b>Email:</b> caroleherman2012@gmail.com</div><div>
|
||
<a href="http://www.alliance-maladies-rares.org/association/amis-de-adnp-france/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">alliance-maladies-rares.org/association/amis-de-adnp-france</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>American Association on Intellectual and Developmental Disabilities (AAIDD)</b>
|
||
</div><div><b>Phone:</b> 202-387-1968</div><div>
|
||
<a href="https://www.aaidd.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aaidd.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>CDC - Child Development</b>
|
||
</div><div><b>Phone:</b> 800-232-4636</div><div>
|
||
<a href="https://www.cdc.gov/child-development/about/developmental-disability-basics.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developmental Disability Basics</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="http://www.nlm.nih.gov/medlineplus/ency/article/001523.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Intellectual Disability</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Simons Searchlight Registry</b>
|
||
</div><div>
|
||
<i>Simons Searchlight aims to further the understanding of rare genetic neurodevelopmental disorders.</i>
|
||
</div><div><b>Phone:</b> 855-329-5638</div><div><b>Fax:</b> 570-214-7327</div><div><b>Email:</b> coordinator@simonssearchlight.org</div><div>
|
||
<a href="https://www.simonssearchlight.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">simonssearchlight.org</a>
|
||
</div></li></ul>
|
||
</div><div id="adnp-dis.Molecular_Genetics"><h2 id="_adnp-dis_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="adnp-dis.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>ADNP-Related Disorder: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_adnp-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_adnp-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_adnp-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_adnp-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_adnp-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_adnp-dis.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/23394" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>ADNP</i>
|
||
</a>
|
||
</td><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=23394" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">20q13<wbr style="display:inline-block"></wbr>.13</a>
|
||
</td><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q9H2P0" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Activity-dependent neuroprotector homeobox protein</a>
|
||
</td><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/ADNP" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADNP database</a>
|
||
</td><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ADNP" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADNP</a>
|
||
</td><td headers="hd_b_adnp-dis.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ADNP[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ADNP</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="adnp-dis.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="adnp-dis.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for ADNP-Related Disorder (<a href="/omim/611386,615873" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/611386" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611386</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ACTIVITY-DEPENDENT NEUROPROTECTOR HOMEOBOX; ADNP</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/615873" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">615873</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HELSMOORTEL-VAN DER AA SYNDROME; HVDAS</td></tr></tbody></table></div></div><div id="adnp-dis.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>ADNP</i> contains five exons, the last three of which are translated. The protein contains nine zinc fingers and three other functional domains, including NAP, an 8-amino-acid neuroprotectant peptide (NAPVSIPQ), a DNA-binding homeobox <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a>, and a HP1-binding motif.</p><p><i>ADNP</i> is a vasoactive intestinal peptide (VIP)-responsive <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>. VIP, a neuroprotective peptide, is active during embryonic development, in particular during the time of neuronal tube closure. It protects damaged nerve cells from cell death by inducing glia-derived, survival-promoting substances [<a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al 2014</a>].</p><p>Wild type ADNP directly binds <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> DNA and mediates the recruitment of the BAF complex through its C-terminal end. The C-terminal end is truncated in all individuals with an <i>ADNP</i>-related disorder. It has been hypothesized that the mutated protein still binds to the DNA, but is no longer capable of recruiting the BAF complex, leading to diminished functionality of the complex as a whole and ultimately to deregulation of several cellular processes [<a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al 2014</a>]. ADNP has also been shown to interact with the chromatin-remodeling <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> <i>CHD4</i> [<a class="bk_pop" href="#adnp-dis.REF.ostapcuk.2018.739">Ostapcuk et al 2018</a>].</p><p><b>Mechanism of disease causation.</b> The mutational mechanism is not known, but it has been hypothesized that the mutated ADNP protein competes with the <a class="def" href="/books/n/gene/glossary/def-item/wild_type/">wild type</a> protein to bind with the BAF complexes (the functional eukaryotic equivalent of the SWI/SNF complex that is involved in the regulation of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> expression in yeast) [<a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al 2014</a>].</p><div id="adnp-dis.T.notable_adnp_pathogenic_varia" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Notable <i>ADNP</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK355518/table/adnp-dis.T.notable_adnp_pathogenic_varia/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__adnp-dis.T.notable_adnp_pathogenic_varia_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_015339.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_015339<wbr style="display:inline-block"></wbr>.5</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_056154.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_056154<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2157C>G</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr719Ter</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pathogenic variant in <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> 4; assoc w/later onset of walking & higher pain threshold than other <i>ADNP</i> pathogenic variants [<a class="bk_pop" href="#adnp-dis.REF.van_dijck.2019.287">Van Dijck et al 2019</a>]</td></tr><tr><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2491_2494delTTAA</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Leu831IlefsTer82</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">All other pathogenic variants are <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> frameshift or <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> variants in the 3′ end of 5th (last) <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> of <i>ADNP</i> & predict a premature termination [<a class="bk_pop" href="#adnp-dis.REF.helsmoortel.2014.380">Helsmoortel et al 2014</a>].</td></tr><tr><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2496_2499delTAAA</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn832LysfsTer81</td></tr><tr><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2188C>T</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg730Ter</td><td headers="hd_h_adnp-dis.T.notable_adnp_pathogenic_varia_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></div></div></div></div></div><div id="adnp-dis.Chapter_Notes"><h2 id="_adnp-dis_Chapter_Notes_">Chapter Notes</h2><div id="adnp-dis.Author_Notes"><h3>Author Notes</h3><p>The research group <a href="https://www.uantwerpen.be/en/rg/cognet/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cognitive Genetics</a> is part of the research cluster Medical Genetics of the Faculty of Pharmaceutical, Biomedical, and Veterinary Sciences of the University of Antwerp. Our mission is to identify genetic causes of cognitive disorders and to study the molecular defects in order to eventually develop rational therapy.</p></div><div id="adnp-dis.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the families with individuals affected by an <i>ADNP</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> who are participating in our research programs.</p></div><div id="adnp-dis.Author_History"><h3>Author History</h3><p>Céline Helsmoortel, MSc; University of Antwerp (2016-2021)<br />Frank Kooy, PhD (2016-present)<br />Anke Van Dijck, MD, PhD (2016-present)<br />Geert Vandeweyer, PhD (2016-present)</p></div><div id="adnp-dis.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>6 October 2022 (sw) Revision: <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> signature analysis (<a href="#adnp-dis.Establishing_the_Diagnosis">Establishing the Diagnosis</a>)</div></li><li class="half_rhythm"><div>15 April 2021 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 April 2016 (bp) Review posted live</div></li><li class="half_rhythm"><div>18 December 2015 (avd) Original submission</div></li></ul></div></div><div id="adnp-dis.References"><h2 id="_adnp-dis_References_">References</h2><div id="adnp-dis.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.arefeshghi.2020.356">Aref-Eshghi E, Kerkhof J, Pedro VP, Groupe DI. France, Barat-Houari M, Ruiz-Pallares N, Andrau JC, Lacombe D, Van-Gils J, Fergelot P, Dubourg C, Cormier-Daire V, Rondeau S, Lecoquierre F, Saugier-Veber P, Nicolas G, Lesca G, Chatron N, Sanlaville D, Vitobello A, Faivre L, Thauvin-Robinet C, Laumonnier F, Raynaud M, Alders M, Mannens M, Henneman P, Hennekam RC, Velasco G, Francastel C, Ulveling D, Ciolfi A, Pizzi S, Tartaglia M, Heide S, Héron D, Mignot C, Keren B, Whalen S, Afenjar A, Bienvenu T, Campeau PM, Rousseau J, Levy MA, Brick L, Kozenko M, Balci TB, Siu VM, Stuart A, Kadour M, Masters J, Takano K, Kleefstra T, de Leeuw N, Field M, Shaw M, Gecz J, Ainsworth PJ, Lin H, Rodenhiser DI, Friez MJ, Tedder M, Lee JA, DuPont BR, Stevenson RE, Skinner SA, Schwartz CE, Genevieve D, Sadikovic B. Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 mendelian neurodevelopmental disorders. <span><span class="ref-journal">Am J Hum Genet. </span>2020;<span class="ref-vol">106</span>:356–70.</span> [<a href="/pmc/articles/PMC7058829/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7058829</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32109418" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32109418</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.bassan.1999.1283">Bassan M, Zamostiano R, Davidson A, Pinhasov A, Giladi E, Perl O, Bassan H, Blat C, Gibney G, Glazner G, Brenneman DE, Gozes I. Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. <span><span class="ref-journal">J Neurochem. </span>1999;<span class="ref-vol">72</span>:1283–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10037502" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10037502</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.bend.2019.64">Bend EG, Aref-Eshghi E, Everman DB, Rogers RC, Cathey SS, Prijoles EJ, Lyons MJ, Davis H, Clarkson K, Gripp KW, Li D, Bhoj E, Zackai E, Mark P, Hakonarson H, Demmer LA, Levy MA, Kerkhof J, Stuart A, Rodenhiser D, Friez MJ, Stevenson RE, Schwartz CE, Sadikovic B. Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome. <span><span class="ref-journal">Clin Epigenetics. </span>2019;<span class="ref-vol">11</span>:64.</span> [<a href="/pmc/articles/PMC6487024/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6487024</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31029150" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31029150</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.breen.2020.555">Breen MS, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, Arnett AB, Kurtz-Nelson E, Agolini E, Battaglia A, Chiocchetti AG, Freitag CM, Garcia-Alcon A, Grammatico P, Hertz-Picciotto I, Ludena-Rodriguez Y, Moreno C, Novelli A, Parellada M, Pascolini G, Tassone F, Grice DE, Di Marino D, Bernier RA, Kolevzon A, Sharp AJ, Buxbaum JD, Siper PM, De Rubeis S. Episignatures stratifying Helsmoortel-Van Der Aa syndrome show modest correlation with phenotype. <span><span class="ref-journal">Am J Hum Genet. </span>2020;<span class="ref-vol">107</span>:555–63.</span> [<a href="/pmc/articles/PMC7477006/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7477006</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32758449" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32758449</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.coe.2014.1063">Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT, Bosco P, Friend KL, Baker C, Buono S, Vissers LE, Schuurs-Hoeijmakers JH, Hoischen A, Pfundt R, Krumm N, Carvill GL, Li D, Amaral D, Brown N, Lockhart PJ, Scheffer IE, Alberti A, Shaw M, Pettinato R, Tervo R, de Leeuw N, Reijnders MR, Torchia BS, Peeters H, O'Roak BJ, Fichera M, Hehir-Kwa JY, Shendure J, Mefford HC, Haan E, Gécz J, de Vries BB, Romano C, Eichler EE. Refining analyses of copy number variation identifies specific genes associated with developmental delay. <span><span class="ref-journal">Nat Genet. </span>2014;<span class="ref-vol">46</span>:1063–71.</span> [<a href="/pmc/articles/PMC4177294/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4177294</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25217958" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25217958</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.de_rubeis.2014.209">De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma'ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. <span><span class="ref-journal">Nature. </span>2014;<span class="ref-vol">515</span>:209–15.</span> [<a href="/pmc/articles/PMC4402723/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4402723</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25363760" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25363760</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group. Large-scale discovery of novel genetic causes of developmental disorders. <span><span class="ref-journal">Nature. </span>2015;<span class="ref-vol">519</span>:223–8.</span> [<a href="/pmc/articles/PMC5955210/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5955210</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25533962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25533962</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.helsmoortel.2014.380">Helsmoortel C, Vulto-van Silfhout AT, Coe BP, Vandeweyer G, Rooms L, van den Ende J, Schuurs-Hoeijmakers JH, Marcelis CL, Willemsen MH, Vissers LE, Yntema HG, Bakshi M, Wilson M, Witherspoon KT, Malmgren H, Nordgren A, Annerén G, Fichera M, Bosco P, Romano C, de Vries BB, Kleefstra T, Kooy RF, Eichler EE, Van der Aa N. A. SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. <span><span class="ref-journal">Nat Genet. </span>2014;<span class="ref-vol">46</span>:380–4.</span> [<a href="/pmc/articles/PMC3990853/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3990853</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24531329" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24531329</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.huynh.2018.1497">Huynh MT, Boudry-Labis E, Massard A, Thuillier C, Delobel B, Duban-Bedu B, Vincent-Delorme C. A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel-van der Aa syndrome. <span><span class="ref-journal">Eur J Hum Genet. </span>2018;<span class="ref-vol">26</span>:1497–501.</span> [<a href="/pmc/articles/PMC6138634/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6138634</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29899371" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29899371</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.ostapcuk.2018.739">Ostapcuk V, Mohn F, Carl SH, Basters A, Hess D, Iesmantavicius V, Lampersberger L, Flemr M, Pandey A, Thomä NH, Betschinger J, Bühler M. Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes. <span><span class="ref-journal">Nature. </span>2018;<span class="ref-vol">557</span>:739–43.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29795351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29795351</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.pescosolido.2014.587">Pescosolido MF, Schwede M, Johnson Harrison A, Schmidt M, Gamsiz ED, Chen WS, Donahue JP, Shur N, Jerskey BA, Phornphutkul C, Morrow EM. Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein. <span><span class="ref-journal">J Med Genet. </span>2014;<span class="ref-vol">51</span>:587–9.</span> [<a href="/pmc/articles/PMC4135390/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4135390</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25057125" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25057125</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.rahbari.2016.126">Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, Dominiczak A, Morris A, Porteous D, Smith B, Stratton MR, Hurles ME, et al. Timing, rates and spectra of human germline mutation. <span><span class="ref-journal">Nat Genet. </span>2016;<span class="ref-vol">48</span>:126–33.</span> [<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.van_dijck.2019.287">Van Dijck A, Vulto-van Silfhout AT, Cappuyns E, van der Werf IM, Mancini GM, Tzschach A, Bernier R, Gozes I, Eichler EE, Romano C, Lindstrand A, Nordgren A., ADNP Consortium. Kvarnung M, Kleefstra T, de Vries BB, Küry S, Rosenfeld JA, Meuwissen ME, Vandeweyer G, Kooy RF. Clinical presentation of a complex neurodevelopmental disorder caused by mutations in ADNP. <span><span class="ref-journal">Biol Psychiatry. </span>2019;<span class="ref-vol">85</span>:287–97.</span> [<a href="/pmc/articles/PMC6139063/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6139063</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29724491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29724491</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.vandeweyer.2014.315">Vandeweyer G, Helsmoortel C, Van Dijck A, Vulto-van Silfhout AT, Coe BP, Bernier R, Gerdts J, Rooms L, van den Ende J, Bakshi M, Wilson M, Nordgren A, Hendon LG, Abdulrahman OA, Romano C, de Vries BB, Kleefstra T, Eichler EE, Van der Aa N, Kooy RF. The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism. <span><span class="ref-journal">Am J Med Genet C Semin Med Genet. </span>2014;<span class="ref-vol">166C</span>:315–26.</span> [<a href="/pmc/articles/PMC4195434/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4195434</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25169753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25169753</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="adnp-dis.REF.vulihshultzman.2007.438">Vulih-Shultzman I, Pinhasov A, Mandel S, Grigoriadis N, Touloumi O, Pittel Z, Gozes I. Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. <span><span class="ref-journal">J Pharmacol Exp Ther. </span>2007;<span class="ref-vol">323</span>:438–49.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17720885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17720885</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
|
||
<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
|
||
a registered trademark of the University of Washington, Seattle. All rights
|
||
reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
|
||
hereby granted to reproduce, distribute, and translate copies of content materials for
|
||
noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
|
||
Washington) are included with each copy; (ii) a link to the original material is provided
|
||
whenever the material is published elsewhere on the Web; and (iii) reproducers,
|
||
distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
||
Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
|
||
of GeneReviews chapters for use in lab reports and clinic notes are a permitted
|
||
use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
||
Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
|
||
contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div><div class="small"><span class="label">Bookshelf ID: NBK355518</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/27054228" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">27054228</a></span></div><div style="margin-top:2em" class="bk_noprnt"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/adcy5-dysk/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/ipa/" title="Next page in this title">Next ></a></div></div></div></div>
|
||
|
||
</div>
|
||
|
||
<!-- Custom content below content -->
|
||
<div class="col4">
|
||
|
||
</div>
|
||
|
||
|
||
<!-- Book content -->
|
||
|
||
<!-- Custom contetnt below bottom nav -->
|
||
<div class="col5">
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div id="rightcolumn" class="four_col col last">
|
||
<!-- Custom content above discovery portlets -->
|
||
<div class="col6">
|
||
<div id="ncbi_share_book"><a href="#" class="ncbi_share" data-ncbi_share_config="popup:false,shorten:true" ref="id=NBK355518&db=books">Share</a></div>
|
||
|
||
</div>
|
||
<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK355518/?report=reader">PubReader</a></li><li><a href="/books/NBK355518/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK355518" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK355518" style="display:none" title="Cite this Page"><div class="bk_tt">Van Dijck A, Vandeweyer G, Kooy F. ADNP-Related Disorder. 2016 Apr 7 [Updated 2022 Oct 6]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></div></div></li><li><a href="/books/NBK355518/pdf/Bookshelf_NBK355518.pdf">PDF version of this page</a> (1.8M)</li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this GeneReview</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#adnp-dis.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#adnp-dis.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#adnp-dis.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#adnp-dis.Genetically_Related_Allelic_Dis" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#adnp-dis.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#adnp-dis.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#adnp-dis.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#adnp-dis.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#adnp-dis.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#adnp-dis.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#adnp-dis.References" ref="log$=inpage&link_id=inpage">References</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Bulk Download</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="https://ftp.ncbi.nlm.nih.gov/pub/litarch/ca/84/" ref="pagearea=source-links&targetsite=external&targetcat=link&targettype=uri">Bulk download GeneReviews data from FTP</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>GeneReviews Links</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="source-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/n/gene/advanced/"><i>GeneReviews</i> Advanced Search</a></li><li><a href="/books/n/gene/glossary/"><i>GeneReviews</i> Glossary</a></li><li><a href="/books/n/gene/resource_mats/">Resource Materials</a> <span class="bk_hlight1">NEW FEATURE</span></li><li><a href="/books/n/gene/updates/">New in <i>GeneReviews</i></a></li><li><a href="/books/n/gene/authors/">Author List</a></li><li><a href="/books/n/gene/prospective_authors/">For Current/Prospective Authors</a></li><li><a href="/books/n/gene/GRpersonnel/"><i>GeneReviews</i> Personnel</a></li><li><a href="/books/n/gene/howto_linkin/">Download/Link to <i>GeneReviews</i></a></li><li><a href="/books/n/gene/contact_us/">Contact Us</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Tests in GTR by Gene</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li>
|
||
<a href="https://www.ncbi.nlm.nih.gov/gtr/tests/?term=23394[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">ADNP</a>
|
||
</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=omim&DbFrom=books&Cmd=Link&LinkName=books_omim&IdsFromResult=4234300" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=4234300" ref="log$=recordlinks">PMC</a><div class="brieflinkpop offscreen_noflow">PubMed Central citations</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pubmed&DbFrom=books&Cmd=Link&LinkName=books_pubmed_refs&IdsFromResult=4234300" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=4234300" ref="log$=recordlinks">Gene</a><div class="brieflinkpop offscreen_noflow">Locus Links</div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Similar articles in PubMed</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PBooksDiscovery_RA" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301377" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phelan-McDermid Syndrome-SHANK3 Related.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Phelan-McDermid Syndrome-SHANK3 Related.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Phelan K, Rogers RC, Boccuto L. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/39083629" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NFIX-Related Malan Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NFIX-Related Malan Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Priolo M. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/38662876" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> CTCF-Related Disorder.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> CTCF-Related Disorder.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Valverde de Morales HG, Wang HL, Garber K, Corces V, Li H. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/28406602" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Myhre Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Myhre Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lin AE, Brunetti-Pierri N, Lindsay ME, Schimmenti LA, Starr LJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301382" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Single Large-Scale Mitochondrial DNA Deletion Syndromes.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Single Large-Scale Mitochondrial DNA Deletion Syndromes.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Goldstein A, Falk MJ. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=27054228" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=27054228" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a href="javascript:historyDisplayState('HTOff')" class="HTOn">Turn Off</a><a href="javascript:historyDisplayState('HTOn')" class="HTOff">Turn On</a></div><ul id="activity"><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d2a90db15b832ebc073105">ADNP-Related Disorder - GeneReviews®</a><div class="ralinkpop offscreen_noflow">ADNP-Related Disorder - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d2a90a84f3725e59245f21">ADCY5 Dyskinesia - GeneReviews®</a><div class="ralinkpop offscreen_noflow">ADCY5 Dyskinesia - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d2a90984f3725e5924524c">ADAMTSL4-Related Eye Disorders - GeneReviews®</a><div class="ralinkpop offscreen_noflow">ADAMTSL4-Related Eye Disorders - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d2a906b15b832ebc0706db">ACTG2 Visceral Myopathy - GeneReviews®</a><div class="ralinkpop offscreen_noflow">ACTG2 Visceral Myopathy - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d2a903b15b832ebc06ee10">AARS2-Related Disorder - GeneReviews®</a><div class="ralinkpop offscreen_noflow">AARS2-Related Disorder - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
|
||
|
||
<!-- Custom content below discovery portlets -->
|
||
<div class="col7">
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<!-- Custom content after all -->
|
||
<div class="col8">
|
||
|
||
</div>
|
||
<div class="col9">
|
||
|
||
</div>
|
||
|
||
<script type="text/javascript" src="/corehtml/pmc/js/jquery.scrollTo-1.4.2.js"></script>
|
||
<script type="text/javascript">
|
||
(function($){
|
||
$('.skiplink').each(function(i, item){
|
||
var href = $($(item).attr('href'));
|
||
href.attr('tabindex', '-1').addClass('skiptarget'); // ensure the target can receive focus
|
||
$(item).on('click', function(event){
|
||
event.preventDefault();
|
||
$.scrollTo(href, 0, {
|
||
onAfter: function(){
|
||
href.focus();
|
||
}
|
||
});
|
||
});
|
||
});
|
||
})(jQuery);
|
||
</script>
|
||
</div>
|
||
<div class="bottom">
|
||
|
||
<div id="NCBIFooter_dynamic">
|
||
<!--<component id="Breadcrumbs" label="breadcrumbs"/>
|
||
<component id="Breadcrumbs" label="helpdesk"/>-->
|
||
|
||
</div>
|
||
|
||
<div class="footer" id="footer">
|
||
<section class="icon-section">
|
||
<div id="icon-section-header" class="icon-section_header">Follow NCBI</div>
|
||
<div class="grid-container container">
|
||
<div class="icon-section_container">
|
||
<a class="footer-icon" id="footer_twitter" href="https://twitter.com/ncbi" aria-label="Twitter"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11 {
|
||
fill: #737373;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>Twitter</title>
|
||
<path class="cls-11" d="M250.11,105.48c-7,3.14-13,3.25-19.27.14,8.12-4.86,8.49-8.27,11.43-17.46a78.8,78.8,0,0,1-25,9.55,39.35,39.35,0,0,0-67,35.85,111.6,111.6,0,0,1-81-41.08A39.37,39.37,0,0,0,81.47,145a39.08,39.08,0,0,1-17.8-4.92c0,.17,0,.33,0,.5a39.32,39.32,0,0,0,31.53,38.54,39.26,39.26,0,0,1-17.75.68,39.37,39.37,0,0,0,36.72,27.3A79.07,79.07,0,0,1,56,223.34,111.31,111.31,0,0,0,116.22,241c72.3,0,111.83-59.9,111.83-111.84,0-1.71,0-3.4-.1-5.09C235.62,118.54,244.84,113.37,250.11,105.48Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_facebook" href="https://www.facebook.com/ncbi.nlm" aria-label="Facebook"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>Facebook</title>
|
||
<path class="cls-11" d="M210.5,115.12H171.74V97.82c0-8.14,5.39-10,9.19-10h27.14V52l-39.32-.12c-35.66,0-42.42,26.68-42.42,43.77v19.48H99.09v36.32h27.24v109h45.41v-109h35Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_linkedin" href="https://www.linkedin.com/company/ncbinlm" aria-label="LinkedIn"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<title>LinkedIn</title>
|
||
<path class="cls-11" d="M101.64,243.37H57.79v-114h43.85Zm-22-131.54h-.26c-13.25,0-21.82-10.36-21.82-21.76,0-11.65,8.84-21.15,22.33-21.15S101.7,78.72,102,90.38C102,101.77,93.4,111.83,79.63,111.83Zm100.93,52.61A17.54,17.54,0,0,0,163,182v61.39H119.18s.51-105.23,0-114H163v13a54.33,54.33,0,0,1,34.54-12.66c26,0,44.39,18.8,44.39,55.29v58.35H198.1V182A17.54,17.54,0,0,0,180.56,164.44Z">
|
||
</path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_github" href="https://github.com/ncbi" aria-label="GitHub"><svg xmlns="http://www.w3.org/2000/svg" data-name="Layer 1" viewBox="0 0 300 300">
|
||
<defs>
|
||
<style>
|
||
.cls-11,
|
||
.cls-12 {
|
||
fill: #737373;
|
||
}
|
||
|
||
.cls-11 {
|
||
fill-rule: evenodd;
|
||
}
|
||
</style>
|
||
</defs>
|
||
<title>GitHub</title>
|
||
<path class="cls-11" d="M151.36,47.28a105.76,105.76,0,0,0-33.43,206.1c5.28,1,7.22-2.3,7.22-5.09,0-2.52-.09-10.85-.14-19.69-29.42,6.4-35.63-12.48-35.63-12.48-4.81-12.22-11.74-15.47-11.74-15.47-9.59-6.56.73-6.43.73-6.43,10.61.75,16.21,10.9,16.21,10.9,9.43,16.17,24.73,11.49,30.77,8.79,1-6.83,3.69-11.5,6.71-14.14C108.57,197.1,83.88,188,83.88,147.51a40.92,40.92,0,0,1,10.9-28.39c-1.1-2.66-4.72-13.42,1-28,0,0,8.88-2.84,29.09,10.84a100.26,100.26,0,0,1,53,0C198,88.3,206.9,91.14,206.9,91.14c5.76,14.56,2.14,25.32,1,28a40.87,40.87,0,0,1,10.89,28.39c0,40.62-24.74,49.56-48.29,52.18,3.79,3.28,7.17,9.71,7.17,19.58,0,14.15-.12,25.54-.12,29,0,2.82,1.9,6.11,7.26,5.07A105.76,105.76,0,0,0,151.36,47.28Z">
|
||
</path>
|
||
<path class="cls-12" d="M85.66,199.12c-.23.52-1.06.68-1.81.32s-1.2-1.06-.95-1.59,1.06-.69,1.82-.33,1.21,1.07.94,1.6Zm-1.3-1">
|
||
</path>
|
||
<path class="cls-12" d="M90,203.89c-.51.47-1.49.25-2.16-.49a1.61,1.61,0,0,1-.31-2.19c.52-.47,1.47-.25,2.17.49s.82,1.72.3,2.19Zm-1-1.08">
|
||
</path>
|
||
<path class="cls-12" d="M94.12,210c-.65.46-1.71,0-2.37-.91s-.64-2.07,0-2.52,1.7,0,2.36.89.65,2.08,0,2.54Zm0,0"></path>
|
||
<path class="cls-12" d="M99.83,215.87c-.58.64-1.82.47-2.72-.41s-1.18-2.06-.6-2.7,1.83-.46,2.74.41,1.2,2.07.58,2.7Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M107.71,219.29c-.26.82-1.45,1.2-2.64.85s-2-1.34-1.74-2.17,1.44-1.23,2.65-.85,2,1.32,1.73,2.17Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M116.36,219.92c0,.87-1,1.59-2.24,1.61s-2.29-.68-2.3-1.54,1-1.59,2.26-1.61,2.28.67,2.28,1.54Zm0,0">
|
||
</path>
|
||
<path class="cls-12" d="M124.42,218.55c.15.85-.73,1.72-2,1.95s-2.37-.3-2.52-1.14.73-1.75,2-2,2.37.29,2.53,1.16Zm0,0"></path>
|
||
</svg></a>
|
||
<a class="footer-icon" id="footer_blog" href="https://ncbiinsights.ncbi.nlm.nih.gov/" aria-label="Blog">
|
||
<svg xmlns="http://www.w3.org/2000/svg" id="Layer_1" data-name="Layer 1" viewBox="0 0 40 40">
|
||
<defs><style>.cls-1{fill:#737373;}</style></defs>
|
||
<title>NCBI Insights Blog</title>
|
||
<path class="cls-1" d="M14,30a4,4,0,1,1-4-4,4,4,0,0,1,4,4Zm11,3A19,19,0,0,0,7.05,15a1,1,0,0,0-1,1v3a1,1,0,0,0,.93,1A14,14,0,0,1,20,33.07,1,1,0,0,0,21,34h3a1,1,0,0,0,1-1Zm9,0A28,28,0,0,0,7,6,1,1,0,0,0,6,7v3a1,1,0,0,0,1,1A23,23,0,0,1,29,33a1,1,0,0,0,1,1h3A1,1,0,0,0,34,33Z"></path>
|
||
</svg>
|
||
</a>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
|
||
<section class="container-fluid bg-primary">
|
||
<div class="container pt-5">
|
||
<div class="row mt-3">
|
||
<div class="col-lg-3 col-12">
|
||
<p><a class="text-white" href="https://www.nlm.nih.gov/socialmedia/index.html">Connect with NLM</a></p>
|
||
<ul class="list-inline social_media">
|
||
<li class="list-inline-item"><a href="https://twitter.com/NLM_NIH" aria-label="Twitter" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st20 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st30 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Twitter</title>
|
||
<g>
|
||
<g>
|
||
<g>
|
||
<path class="st20" d="M192.9,88.1c-5,2.2-9.2,2.3-13.6,0.1c5.7-3.4,6-5.8,8.1-12.3c-5.4,3.2-11.4,5.5-17.6,6.7 c-10.5-11.2-28.1-11.7-39.2-1.2c-7.2,6.8-10.2,16.9-8,26.5c-22.3-1.1-43.1-11.7-57.2-29C58,91.6,61.8,107.9,74,116 c-4.4-0.1-8.7-1.3-12.6-3.4c0,0.1,0,0.2,0,0.4c0,13.2,9.3,24.6,22.3,27.2c-4.1,1.1-8.4,1.3-12.5,0.5c3.6,11.3,14,19,25.9,19.3 c-11.6,9.1-26.4,13.2-41.1,11.5c12.7,8.1,27.4,12.5,42.5,12.5c51,0,78.9-42.2,78.9-78.9c0-1.2,0-2.4-0.1-3.6 C182.7,97.4,189.2,93.7,192.9,88.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st30" cx="124.4" cy="128.8" r="108.2"></circle>
|
||
</g>
|
||
</svg></a></li>
|
||
<li class="list-inline-item"><a href="https://www.facebook.com/nationallibraryofmedicine" aria-label="Facebook" rel="noopener noreferrer" target="_blank">
|
||
<svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<style type="text/css">
|
||
.st10 {
|
||
fill: #FFFFFF;
|
||
}
|
||
|
||
.st110 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
</style>
|
||
<title>Facebook</title>
|
||
<g>
|
||
<g>
|
||
<path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path>
|
||
</g>
|
||
</g>
|
||
<circle class="st110" cx="123.6" cy="123.2" r="108.2"></circle>
|
||
</svg>
|
||
</a></li>
|
||
<li class="list-inline-item"><a href="https://www.youtube.com/user/NLMNIH" aria-label="Youtube" target="_blank" rel="noopener noreferrer"><svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" version="1.1" x="0px" y="0px" viewBox="0 0 249 249" style="enable-background:new 0 0 249 249;" xml:space="preserve">
|
||
<title>Youtube</title>
|
||
<style type="text/css">
|
||
.st4 {
|
||
fill: none;
|
||
stroke: #FFFFFF;
|
||
stroke-width: 8;
|
||
stroke-miterlimit: 10;
|
||
}
|
||
|
||
.st5 {
|
||
fill: #FFFFFF;
|
||
}
|
||
</style>
|
||
<circle class="st4" cx="124.2" cy="123.4" r="108.2"></circle>
|
||
<g transform="translate(0,-952.36218)">
|
||
<path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path>
|
||
</g>
|
||
</svg></a></li>
|
||
</ul>
|
||
</div>
|
||
<div class="col-lg-3 col-12">
|
||
<p class="address_footer text-white">National Library of Medicine<br />
|
||
<a href="https://www.google.com/maps/place/8600+Rockville+Pike,+Bethesda,+MD+20894/@38.9959508,-77.101021,17z/data=!3m1!4b1!4m5!3m4!1s0x89b7c95e25765ddb:0x19156f88b27635b8!8m2!3d38.9959508!4d-77.0988323" class="text-white" target="_blank" rel="noopener noreferrer">8600 Rockville Pike<br />
|
||
Bethesda, MD 20894</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
|
||
<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
|
||
<a href="https://www.hhs.gov/vulnerability-disclosure-policy/index.html" class="text-white" id="vdp">HHS Vulnerability Disclosure</a></p>
|
||
</div>
|
||
<div class="col-lg-3 col-12 centered-lg">
|
||
<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
|
||
<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
|
||
<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
|
||
</div>
|
||
</div>
|
||
<div class="row">
|
||
<div class="col-lg-12 centered-lg">
|
||
<nav class="bottom-links">
|
||
<ul class="mt-3">
|
||
<li>
|
||
<a class="text-white" href="//www.nlm.nih.gov/">NLM</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.nih.gov/">NIH</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.hhs.gov/">HHS</a>
|
||
</li>
|
||
<li>
|
||
<a class="text-white" href="https://www.usa.gov/">USA.gov</a>
|
||
</li>
|
||
</ul>
|
||
</nav>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
</section>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentOmnitureBaseJS/InstrumentNCBIConfigJS/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js?v=1"> </script>
|
||
<script type="text/javascript" src="/portal/portal3rc.fcgi/static/js/hfjs2.js"> </script>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<!--/.page-->
|
||
</div>
|
||
<!--/.wrap-->
|
||
</div><!-- /.twelve_col -->
|
||
</div>
|
||
<!-- /.grid -->
|
||
|
||
<span class="PAFAppResources"></span>
|
||
|
||
<!-- BESelector tab -->
|
||
|
||
|
||
|
||
<noscript><img alt="statistics" src="/stat?jsdisabled=true&ncbi_db=books&ncbi_pdid=book-part&ncbi_acc=NBK355518&ncbi_domain=gene&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK355518/&ncbi_pagename=ADNP-Related Disorder - GeneReviews® - NCBI Bookshelf&ncbi_bookparttype=chapter&ncbi_app=bookshelf" /></noscript>
|
||
|
||
|
||
<!-- usually for JS scripts at page bottom -->
|
||
<!--<component id="PageFixtures" label="styles"></component>-->
|
||
|
||
|
||
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal107 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
||
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
||
|
||
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3879255/4121861/3501987/4008961/3893018/3821238/4062932/4209313/4212053/4076480/3921943/3400083/3426610.js" snapshot="books"></script></body>
|
||
</html> |