597 lines
No EOL
126 KiB
HTML
597 lines
No EOL
126 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="NBK537721" /><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="/NBK537721/" /><meta name="ncbi_pagename" content="SYNGAP1-Related Intellectual Disability - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
|
||
<!-- Logger end -->
|
||
|
||
<title>SYNGAP1-Related Intellectual Disability - 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="SYNGAP1-Related Intellectual Disability" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2019/02/21" /><meta name="citation_author" content="J Lloyd Holder, Jr" /><meta name="citation_author" content="Fadi F Hamdan" /><meta name="citation_author" content="Jacques L Michaud" /><meta name="citation_pmid" content="30789692" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK537721/" /><meta name="citation_keywords" content="SYNGAP1-Related Developmental and Epileptic Encephalopathy" /><meta name="citation_keywords" content="SYNGAP1-Related Developmental and Epileptic Encephalopathy" /><meta name="citation_keywords" content="Ras/Rap GTPase-activating protein SynGAP" /><meta name="citation_keywords" content="SYNGAP1" /><meta name="citation_keywords" content="SYNGAP1-Related Intellectual Disability" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="SYNGAP1-Related Intellectual Disability" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="J Lloyd Holder, Jr" /><meta name="DC.Contributor" content="Fadi F Hamdan" /><meta name="DC.Contributor" content="Jacques L Michaud" /><meta name="DC.Date" content="2019/02/21" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK537721/" /><meta name="description" content="SYNGAP1-related intellectual disability (SYNGAP1-ID) is characterized by developmental delay (DD) or intellectual disability (ID) (100% of affected individuals), generalized epilepsy (~84%), and autism spectrum disorder (ASD) and other behavioral abnormalities (≤50%). To date more than 50 individuals with SYNGAP1-ID have been reported. In the majority DD/ID was moderate to severe; in some it was mild. The epilepsy is generalized; a subset of individuals with epilepsy have myoclonic astatic epilepsy (Doose syndrome) or epilepsy with myoclonic absences. Behavioral abnormalities can include stereotypic behaviors (e.g., hand flapping, obsessions with certain objects) as well as poor social development. Feeding difficulties can be significant in some." /><meta name="og:title" content="SYNGAP1-Related Intellectual Disability" /><meta name="og:type" content="book" /><meta name="og:description" content="SYNGAP1-related intellectual disability (SYNGAP1-ID) is characterized by developmental delay (DD) or intellectual disability (ID) (100% of affected individuals), generalized epilepsy (~84%), and autism spectrum disorder (ASD) and other behavioral abnormalities (≤50%). To date more than 50 individuals with SYNGAP1-ID have been reported. In the majority DD/ID was moderate to severe; in some it was mild. The epilepsy is generalized; a subset of individuals with epilepsy have myoclonic astatic epilepsy (Doose syndrome) or epilepsy with myoclonic absences. Behavioral abnormalities can include stereotypic behaviors (e.g., hand flapping, obsessions with certain objects) as well as poor social development. Feeding difficulties can be significant in some." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK537721/" /><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/syngap1-id/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK537721/" /><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="CE8EB3957D2A29B100000000013A0106.m_12" />
|
||
<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="#__NBK537721_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK537721_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/syne1ca-ar/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/scs/" 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="_NBK537721_"><span class="title" itemprop="name"><i>SYNGAP1</i>-Related Intellectual Disability</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>SYNGAP1</i>-Related Developmental and Epileptic Encephalopathy</div><p class="contrib-group"><span itemprop="author">J Lloyd Holder, Jr</span>, MD, PhD, <span itemprop="author">Fadi F Hamdan</span>, PhD, and <span itemprop="author">Jacques L Michaud</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK537721_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK537721_ai__"><div class="contrib half_rhythm"><span itemprop="author">J Lloyd Holder, Jr</span>, MD, PhD<div class="affiliation small">Texas Children's Hospital<br />Houston, Texas<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.mcb@redloh" class="oemail">ude.mcb@redloh</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Fadi F Hamdan</span>, PhD<div class="affiliation small">CHU Ste-Justine Research Center<br />Montreal, Quebec, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.cq.enitsuj-ets-ehcrehcer@nadmah.idaf" class="oemail">ac.cq.enitsuj-ets-ehcrehcer@nadmah.idaf</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jacques L Michaud</span>, MD<div class="affiliation small">CHU Ste-Justine Research Center<br />Montreal, Quebec, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.cq.enitsuj-ets-ehcrehcer@duahcim.seuqcaj" class="oemail">ac.cq.enitsuj-ets-ehcrehcer@duahcim.seuqcaj</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">February 21, 2019</span>.</p><p><em>Estimated reading time: 17 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="syngap1-id.Summary" itemprop="description"><h2 id="_syngap1-id_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>SYNGAP1</i>-related intellectual disability (<i>SYNGAP1-</i>ID) is characterized by developmental delay (DD) or intellectual disability (ID) (100% of affected individuals), generalized epilepsy (~84%), and autism spectrum disorder (ASD) and other behavioral abnormalities (≤50%). To date more than 50 individuals with <i>SYNGAP1-</i>ID have been reported. In the majority DD/ID was moderate to severe; in some it was mild. The epilepsy is generalized; a subset of individuals with epilepsy have myoclonic astatic epilepsy (Doose syndrome) or epilepsy with myoclonic absences. Behavioral abnormalities can include stereotypic behaviors (e.g., hand flapping, obsessions with certain objects) as well as poor social development. Feeding difficulties can be significant in some.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of <i>SYNGAP1-</i>ID is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with developmental delay or intellectual disability in whom <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> identifies either a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SYNGAP1</i> (~89%) or a <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of 6p21.3 (~11%).</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> DD/ID are managed as per standard practice. No guidelines are available regarding choice of specific anti-seizure medications (ASMs). In about 50% of patients, the epilepsy responds to a single ASM; in the remainder it is pharmacoresistant. Children may qualify for and benefit from interventions used in treatment of ASD. Consultation with a developmental pediatrician may guide parents through appropriate behavioral management strategies and/or provide prescription medications when necessary. Nasogastric/gastrostomy feeding may be required for individuals with persistent feeding issues.</p><p><i>Surveillance:</i> Monitor seizure manifestations and control; behavioral issues; developmental progress and educational needs.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>SYNGAP1-</i>ID is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. To date almost all probands with <i>SYNGAP1-</i>ID whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have had 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/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>; however, vertical transmission (from a mildly affected, mosaic parent to the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>) has been reported in one family. Thus, while the risk to sibs appears to be low, it is presumed to be greater than in the general population because of the possibility of <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a parent. Once the <i>SYNGAP1</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> for a pregnancy at increased risk 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="syngap1-id.Diagnosis"><h2 id="_syngap1-id_Diagnosis_">Diagnosis</h2><p>No formal diagnostic criteria have been published for <i>SYNGAP1</i>-related intellectual disability.</p><div id="syngap1-id.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>SYNGAP1</i>-related intellectual disability (<i>SYNGAP1-</i>ID) <b>should be considered</b> in individuals with developmental delay or intellectual disability with or without:</p><ul><li class="half_rhythm"><div>Generalized epilepsy;</div><div>and/or</div></li><li class="half_rhythm"><div>Autism spectrum disorder (ASD).</div></li></ul></div><div id="syngap1-id.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>SYNGAP1-</i>ID <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with developmental delay (DD) or intellectual disability (ID) in whom <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK537721/table/syngap1-id.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobsyngap1idTmoleculargenetictestingu">Table 1</a>) identifies either:</p><ul><li class="half_rhythm"><div>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>SYNGAP1</i> (~89%);</div><div>or</div></li><li class="half_rhythm"><div>A <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of 6p21.3 (~11%).</div></li></ul><p>Note: 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="#syngap1-id.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants.</p><p><b>Molecular genetic testing</b> in a child with DD or an older individual with ID 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>. Note: 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>SYNGAP1</i>, followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>) is rarely useful and typically NOT recommended.</p><p><b>CMA</b> uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>SYNGAP1</i>) that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>. Note: 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 6p21.32 region.</p><p><b>An ID <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>SYNGAP1</i> and other genes of interest (see <a href="#syngap1-id.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition in a person with a nondiagnostic CMA 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. For this disorder, an ID multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK537721/table/syngap1-id.T.molecular_genetic_testing_u/?report=objectonly" target="object" rid-ob="figobsyngap1idTmoleculargenetictestingu">Table 1</a>).</p><p>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>.</p><p><b>Exome sequencing,</b> which does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved, has the advantage over an ID <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a> of detecting variants in recently identified rare genes not yet included in some ID multigene panels.</p><p>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>.</p><div id="syngap1-id.T.molecular_genetic_testing_u" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>SYNGAP1</i>-Related Intellectual Disability</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK537721/table/syngap1-id.T.molecular_genetic_testing_u/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__syngap1-id.T.molecular_genetic_testing_u_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_syngap1-id.T.molecular_genetic_testing_u_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_syngap1-id.T.molecular_genetic_testing_u_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_syngap1-id.T.molecular_genetic_testing_u_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 <sup>3</sup></th></tr></thead><tbody><tr><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SYNGAP1</i>
|
||
</td><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></td><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">49/55 (89%)</td></tr><tr><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_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_syngap1-id.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown; see footnote 6.</td></tr><tr><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Chromosomal microarray analysis <sup>7</sup></td><td headers="hd_h_syngap1-id.T.molecular_genetic_testing_u_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">6/55 (11%)</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="syngap1-id.TF.1.1"><p class="no_margin">See <a href="/books/NBK537721/#syngap1-id.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="syngap1-id.TF.1.2"><p class="no_margin">Based on a review of published series and case reports</p></div></dd><dt>3. </dt><dd><div id="syngap1-id.TF.1.3"><p class="no_margin"><a class="bk_pop" href="#syngap1-id.REF.krepischi.2010.2376">Krepischi et al [2010]</a>, <a class="bk_pop" href="#syngap1-id.REF.pinto.2010.368">Pinto et al [2010]</a>, <a class="bk_pop" href="#syngap1-id.REF.vissers.2010.1109">Vissers et al [2010]</a>, <a class="bk_pop" href="#syngap1-id.REF.hamdan.2011a.898">Hamdan et al [2011a]</a>, <a class="bk_pop" href="#syngap1-id.REF.hamdan.2011b.306">Hamdan et al [2011b]</a>, <a class="bk_pop" href="#syngap1-id.REF.klitten.2011.e190">Klitten et al [2011]</a>, <a class="bk_pop" href="#syngap1-id.REF.zollino.2011.239">Zollino et al [2011]</a>, <a class="bk_pop" href="#syngap1-id.REF.de_ligt.2012.1921">de Ligt et al [2012]</a>, <a class="bk_pop" href="#syngap1-id.REF.rauch.2012.1674">Rauch et al [2012]</a>, <a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al [2013]</a>, <a class="bk_pop" href="#syngap1-id.REF.carvill.2013.825">Carvill et al [2013]</a>, <a class="bk_pop" href="#syngap1-id.REF.writzl.2013.1682">Writzl & Knegt [2013]</a>, <a class="bk_pop" href="#syngap1-id.REF.redin.2014.724">Redin et al [2014]</a>, <a class="bk_pop" href="#syngap1-id.REF.parker.2015.2231">Parker et al [2015]</a>, <a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al [2016]</a>, <a class="bk_pop" href="#syngap1-id.REF.prchalova.2017.62">Prchalova et al [2017]</a></p></div></dd><dt>4. </dt><dd><div id="syngap1-id.TF.1.4"><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>5. </dt><dd><div id="syngap1-id.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="syngap1-id.TF.1.6"><p class="no_margin">Gene-targeted methods will detect deletions of a single <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> up to a whole <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>; however, breakpoints of large deletions and/or <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> of adjacent genes may not be determined. If a whole-gene deletion is detected by a gene-targeted deletion/<a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> assay, CMA is needed to determine the size of the deletion.</p></div></dd><dt>7. </dt><dd><div id="syngap1-id.TF.1.7"><p class="no_margin">Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 6p21.3 region; however, some 6p21.3 deletions may not have been detectable by older oligonucleotide or BAC platforms.</p></div></dd></dl></div></div></div></div></div><div id="syngap1-id.Clinical_Characteristics"><h2 id="_syngap1-id_Clinical_Characteristics_">Clinical Characteristics</h2><div id="syngap1-id.Clinical_Description"><h3>Clinical Description</h3><p>Since the original description of <i>SYNGAP1</i>-related intellectual disability (<i>SYNGAP1-</i>ID) in three individuals [<a class="bk_pop" href="#syngap1-id.REF.hamdan.2009.599">Hamdan et al 2009</a>], more than 50 affected individuals with detailed clinical information have been reported [<a class="bk_pop" href="#syngap1-id.REF.krepischi.2010.2376">Krepischi et al 2010</a>, <a class="bk_pop" href="#syngap1-id.REF.pinto.2010.368">Pinto et al 2010</a>, <a class="bk_pop" href="#syngap1-id.REF.vissers.2010.1109">Vissers et al 2010</a>, <a class="bk_pop" href="#syngap1-id.REF.hamdan.2011a.898">Hamdan et al 2011a</a>, <a class="bk_pop" href="#syngap1-id.REF.hamdan.2011b.306">Hamdan et al 2011b</a>, <a class="bk_pop" href="#syngap1-id.REF.klitten.2011.e190">Klitten et al 2011</a>, <a class="bk_pop" href="#syngap1-id.REF.zollino.2011.239">Zollino et al 2011</a>, <a class="bk_pop" href="#syngap1-id.REF.de_ligt.2012.1921">de Ligt et al 2012</a>, <a class="bk_pop" href="#syngap1-id.REF.rauch.2012.1674">Rauch et al 2012</a>, <a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>, <a class="bk_pop" href="#syngap1-id.REF.carvill.2013.825">Carvill et al 2013</a>, <a class="bk_pop" href="#syngap1-id.REF.writzl.2013.1682">Writzl & Knegt 2013</a>, <a class="bk_pop" href="#syngap1-id.REF.redin.2014.724">Redin et al 2014</a>, <a class="bk_pop" href="#syngap1-id.REF.parker.2015.2231">Parker et al 2015</a>, <a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al 2016</a>, <a class="bk_pop" href="#syngap1-id.REF.prchalova.2017.62">Prchalova et al 2017</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><p><b>Developmental delay and intellectual disability.</b> The great majority of affected children present with developmental delay or intellectual disability that is typically moderate to severe but can be mild.</p><p>Early motor development is characterized by hypotonia. The average age at walking was 26 months (range: 10.5 months to 5 years). A subset of these children had an ataxic gait that remained stable or improved over time.</p><p>Language is generally impaired; a third of individuals age five years or more remain nonverbal. In those who are verbal, language development ranges from use of single words only to four-to-five-word sentences.</p><p><b>Epilepsy.</b> Approximately 84% of individuals with <i>SYNGAP1-</i>ID have generalized epilepsy; a subset of these were diagnosed with myoclonic astatic epilepsy (Doose syndrome) or epilepsy with myoclonic absences [<a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al 2016</a>].</p><p>While the epilepsy responds to a single anti-seizure medication in approximately half of affected individuals, it is pharmacoresistant in the remainder. Children with refractory seizures may be diagnosed with epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity).</p><ul><li class="half_rhythm"><div><b>Age at onset of seizures</b> varies between six months and seven years; mean age of seizure onset was 3.5 years in one study [<a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al 2016</a>].</div></li><li class="half_rhythm"><div><b>Seizure types</b> include typical or atypical seizures, myoclonic jerks with or without falls, eyelid myoclonia, tonic-clonic seizures, myoclonic absences, and atonic seizures. In one study, Doose syndrome (myoclonic astatic epilepsy) was diagnosed in three of 17 individuals [<a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al 2016</a>].</div></li><li class="half_rhythm"><div><b>Electroencephalography</b> typically shows generalized epileptic activity, frequently with a posterior predominance. Photosensitivity and fixation-off phenomenon have been observed in a number of individuals.</div></li><li class="half_rhythm"><div><b>Brain MRI</b> is typically normal; in rare cases, brain atrophy or delayed myelination has been reported.</div></li></ul><p><b>Autism spectrum disorder (ASD) and other behavioral abnormalities.</b> The occurrence of ASD could be as high as 50%. This includes stereotypic behaviors such as hand flapping, obsessions with certain objects, and poor social development. In addition, inattention, impulsivity, self-directed and other-directed aggressive behavior, elevated pain threshold, hyperacusis, and sleep disorders have been observed.</p><p><b>Other associated features</b> include the following:</p><ul><li class="half_rhythm"><div><b>Acquired microcephaly</b> observed in a minority of affected individuals</div></li><li class="half_rhythm"><div><b>Eye abnormalities</b> including strabismus</div></li><li class="half_rhythm"><div><b>Musculoskeletal disorders</b> including hip rotation or dysplasia, kyphoscoliosis, and <i>pes planus</i></div></li><li class="half_rhythm"><div><b>Hypertrichosis</b> (predominantly on the limbs and lower spine) occasionally described</div></li><li class="half_rhythm"><div><b>Gastrointestinal dysfunction</b> (including constipation requiring medical intervention) frequently reported; swallowing difficulties rarely reported</div></li><li class="half_rhythm"><div><b>Craniofacial features.</b> Although some authors have suggested a subtle but consistent facial appearance (almond-shaped palpebral fissures, mildly myopathic and open-mouthed appearance) [<a class="bk_pop" href="#syngap1-id.REF.parker.2015.2231">Parker et al 2015</a>], it is unclear if these changes are distinct enough to allow a clinician to suspect the condition in a child.</div></li></ul><p><b>Life span.</b> It is unknown if life span in <i>SYNGAP1-</i>ID is abnormal. One reported individual is alive at age 31 years [<a class="bk_pop" href="#syngap1-id.REF.prchalova.2017.62">Prchalova et al 2017</a>], demonstrating that survival into adulthood is possible. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.</p></div><div id="syngap1-id.GenotypePhenotype_Correlation"><h3>Genotype-Phenotype Correlations</h3><p>No definitive <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>-<a class="def" href="/books/n/gene/glossary/def-item/genotype/">genotype</a> correlation between the type of <i>SYNGAP1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> (<a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, truncating, large intragenic <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a>) and cognitive abilities or the occurrence of comorbidities has been observed.</p></div><div id="syngap1-id.Penetrance"><h3>Penetrance</h3><p>Penetrance is 100%. All individuals with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>SYNGAP1</i> have developmental delay, cognitive dysfunction, intellectual disability, and/or epilepsy.</p></div><div id="syngap1-id.Prevalence"><h3>Prevalence</h3><p>The prevalence of <i>SYNGAP1</i> pathogenic variants in two studies was:</p><ul><li class="half_rhythm"><div>1% in a series of 500 individuals with epileptic encephalopathy [<a class="bk_pop" href="#syngap1-id.REF.carvill.2013.825">Carvill et al 2013</a>];</div></li><li class="half_rhythm"><div>0.75% in a large series of 931 unrelated children with intellectual disability [<a class="bk_pop" href="#syngap1-id.REF.fitzgerald.2015.223">Fitzgerald et al 2015</a>].</div></li></ul></div></div><div id="syngap1-id.Genetically_Related_Allelic_D"><h2 id="_syngap1-id_Genetically_Related_Allelic_D_">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>SYNGAP1</i>.</p></div><div id="syngap1-id.Differential_Diagnosis"><h2 id="_syngap1-id_Differential_Diagnosis_">Differential Diagnosis</h2><p>The <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> associated with <i>SYNGAP1</i>-related intellectual disability (ID) overlaps with that of other disorders of ID and epileptic encephalopathy.</p><p>Most genes known to be associated with ID (see <a href="https://omim.org/phenotypicSeries/PS156200" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM Autosomal Dominant Intellectual Developmental Disorder Phenotypic Series</a>) and epileptic encephalopathy (see <a href="http://omim.org/phenotypicSeries/PS308350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM Epileptic Encephalopathy, Early Infantile Phenotypic Series</a>) if compatible with walking should be included in the differential diagnosis.</p></div><div id="syngap1-id.Management"><h2 id="_syngap1-id_Management_">Management</h2><div id="syngap1-id.Evaluations_Following_Initial"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>SYNGAP1</i>-related intellectual disability, the evaluations summarized in <a href="/books/NBK537721/table/syngap1-id.T.recommended_evaluations_fol/?report=objectonly" target="object" rid-ob="figobsyngap1idTrecommendedevaluationsfol">Table 2</a> (if not performed as part of the evaluation that led to diagnosis) are recommended.</p><div id="syngap1-id.T.recommended_evaluations_fol" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>SYNGAP1</i>-Related Intellectual Disability</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK537721/table/syngap1-id.T.recommended_evaluations_fol/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__syngap1-id.T.recommended_evaluations_fol_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_syngap1-id.T.recommended_evaluations_fol_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_syngap1-id.T.recommended_evaluations_fol_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ophthalmologic eval</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Evidence of strabismus</td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_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_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Baseline eval for reflux &/or constipation; assessment for feeding problems</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Refer to gastroenterologist &/or feeding therapist for treatment if indicated.</td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_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_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for hip rotation/dysplasia, kyphoscoliosis, <i>pes planus</i></td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_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_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl EEG & brain MRI if seizures are suspected</td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_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_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Screen persons age >12 mos for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD.</td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Miscellaneous/</b>
|
||
<br />
|
||
<b>Other</b>
|
||
</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl motor, speech/language eval, general cognitive, & vocational skills.</td></tr><tr><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Consultation w/clinical geneticist &/or genetic counselor</td><td headers="hd_h_syngap1-id.T.recommended_evaluations_fol_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</p></div></dd></dl></div></div></div></div><div id="syngap1-id.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div id="syngap1-id.T.treatment_of_manifestations" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>SYNGAP1</i>-Related Intellectual Disability</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK537721/table/syngap1-id.T.treatment_of_manifestations/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__syngap1-id.T.treatment_of_manifestations_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Manifestation/Concern</th><th id="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Treatment</th><th id="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Strabismus</b>
|
||
</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_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_syngap1-id.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Swallowing dysfunction</b>
|
||
</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nasogastric/gastrostomy feeding may be required for persistent feeding issues.</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constipation</b>
|
||
</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment as recommended by gastroenterologist</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology consultation, if severe</td></tr><tr><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hip rotation/dysplasia, kyphoscoliosis, & <i>pes planus</i></b>
|
||
</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment as recommended by orthopedist</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Orthopedic consultation may be considered.</td></tr><tr><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Epilepsy</b>
|
||
</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASMs by experienced neurologist</td><td headers="hd_h_syngap1-id.T.treatment_of_manifestations_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To date, no guidelines on choice of specific ASMs</div></li><li class="half_rhythm"><div>Anecdotal reports of improved seizure control w/ketogenic diet in some persons</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASMs = anti-seizure medications</p></div></dd></dl></div></div></div><p>Education of parents regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for parents or caregivers of 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 id="syngap1-id.Developmental_Delay__Intellec"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy. In the US, early intervention is a federally funded program available in all states.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed.</p><p>
|
||
<b>Ages 5-21 years</b>
|
||
</p><ul><li class="half_rhythm"><div>In the US, an IEP based on the individual's level of function should be developed by the local public school district. Affected children are permitted to remain in the public school district until age 21.</div></li><li class="half_rhythm"><div>Discussion about transition plans including financial, vocation/employment, and medical arrangements should begin at age 12 years. Developmental pediatricians can provide assistance with transition to adulthood.</div></li></ul><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies and to support parents in maximizing quality of life.</p><p>Consideration of private supportive therapies based on the affected individual's needs is recommended. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</p><p>In the US:</p><ul><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="syngap1-id.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction.</b> Assuming that the individual is safe to eat by mouth, feeding therapy – typically from an occupational or speech therapist – is recommended for affected individuals who have difficulty feeding because of poor oral motor control.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties.</p></div><div id="syngap1-id.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and is typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="syngap1-id.Surveillance"><h3>Surveillance</h3><p>Monitor those with seizures as clinically indicated.</p><p>Assess as needed for anxiety, attention, and aggressive or self-injurious behavior.</p><p>Monitor developmental progress and educational needs.</p></div><div id="syngap1-id.Evaluation_of_Relatives_at_Ri"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#syngap1-id.Related_Genetic_Counseling_Is">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="syngap1-id.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><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. Note: There may not be clinical trials for this disorder.</p></div></div><div id="syngap1-id.Genetic_Counseling"><h2 id="_syngap1-id_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="syngap1-id.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>SYNGAP1</i>-related intellectual disability (<i>SYNGAP1-</i>ID) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner and is 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="syngap1-id.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>Almost all probands with <i>SYNGAP1-</i>ID reported to date 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 a result of 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/germline/">germline</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Vertical transmission (from a mildly affected, mosaic parent to the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>) has been reported in one family to date [<a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an apparent <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>.</div></li><li class="half_rhythm"><div>If the <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 proband most likely has a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> pathogenic variant. Parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> is also a possible explanation; paternal somatic and germline mosaicism has been reported in one family [<a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>].</div></li><li class="half_rhythm"><div>Note: If the parent is the individual in whom the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> first occurred, the parent may have both somatic and <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> for the variant and may be mildly affected [<a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>].</div></li></ul><p>
|
||
<b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>The risk to the sibs of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> depends on the genetic status of the proband's parents.</div></li><li class="half_rhythm"><div>Most affected individuals reported to date have had a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>
|
||
<i>SYNGAP1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, suggesting a low risk to sibs. However, because of the possibility of <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a parent, the risk is presumed to be greater than in the general population [<a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>].</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Individuals with <i>SYNGAP1</i>-ID are not known to reproduce; the theoretic risk to offspring of mildly affected mosaic individuals [<a class="bk_pop" href="#syngap1-id.REF.berryer.2013.385">Berryer et al 2013</a>] is up to 50%.</p><p><b>Other family members.</b> Given that most probands with <i>SYNGAP1-</i>ID reported to date have the disorder as a result of 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>, the risk to other family members is presumed to be low.</p></div><div id="syngap1-id.Related_Genetic_Counseling_Is"><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 parents of affected individuals.</div></li></ul></div><div id="syngap1-id.Prenatal_Testing_and_Preimpla"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SYNGAP1</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="syngap1-id.Resources"><h2 id="_syngap1-id_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>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>SYNGAP1 Foundation</b>
|
||
</div><div><b>Phone:</b> 240-347-0302</div><div><b>Email:</b> admin@syngap1foundation.org</div><div>
|
||
<a href="https://syngap1foundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.syngap1foundation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>VOR: Speaking out for people with intellectual and developmental disabilities</b>
|
||
</div><div><b>Phone:</b> 877-399-4867</div><div><b>Email:</b> info@vor.net</div><div>
|
||
<a href="http://www.vor.net/index.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">vor.net</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>VOR: Speaking out for people with intellectual and developmental disabilities</b>
|
||
</div><div><b>Phone:</b> 877-399-4867</div><div><b>Email:</b> info@vor.net</div><div>
|
||
<a href="http://www.vor.net/index.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">vor.net</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>SYNGAP1 (MRD5) Patient Registry</b>
|
||
</div><div>
|
||
<a href="https://syngap1registry.iamrare.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.syngap1registry.iamrare.org</a>
|
||
</div></li></ul>
|
||
</div><div id="syngap1-id.Molecular_Genetics"><h2 id="_syngap1-id_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="syngap1-id.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>SYNGAP1-Related Intellectual Disability: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK537721/table/syngap1-id.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__syngap1-id.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_syngap1-id.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_syngap1-id.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_syngap1-id.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_syngap1-id.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_syngap1-id.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_syngap1-id.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_syngap1-id.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/8831" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>SYNGAP1</i>
|
||
</a>
|
||
</td><td headers="hd_b_syngap1-id.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=8831" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">6p21<wbr style="display:inline-block"></wbr>.32</a>
|
||
</td><td headers="hd_b_syngap1-id.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q96PV0" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Ras/Rap GTPase-activating protein SynGAP</a>
|
||
</td><td headers="hd_b_syngap1-id.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://lovd.nl/SYNGAP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SYNGAP1 database</a>
|
||
</td><td headers="hd_b_syngap1-id.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=SYNGAP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SYNGAP1</a>
|
||
</td><td headers="hd_b_syngap1-id.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SYNGAP1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SYNGAP1</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="syngap1-id.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="syngap1-id.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for SYNGAP1-Related Intellectual Disability (<a href="/omim/603384,612621" 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/NBK537721/table/syngap1-id.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__syngap1-id.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/603384" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603384</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SYNAPTIC RAS-GTPase-ACTIVATING PROTEIN 1; SYNGAP1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/612621" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">612621</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5; MRD5</td></tr></tbody></table></div></div><p><b>Gene structure.</b> To date two NCBI reference sequences for human <i>SYNGAP1</i> have been reported:</p><ul><li class="half_rhythm"><div><a href="https://www.ncbi.nlm.nih.gov/nuccore/194248067" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006772.2</a> (isoform 1) consists of 19 exons and encodes a protein of 1,343 amino acids (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_006763.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_006763.2</a>).</div></li><li class="half_rhythm"><div><a href="https://www.ncbi.nlm.nih.gov/nuccore/194248069" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001130066.1</a> (isoform 2) consists of 18 exons resulting in a protein of 1,292 amino acids (<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001123538.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001123538.1</a>).</div></li></ul><p>Molecular genetic testing for <i>SYNGAP1</i> pathogenic variants should include all 19 exons present in its largest reference sequence isoform (NM_006772.2).</p><p>By comparing human and rodent <i>SYNGAP1</i> cDNAs, <a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al [2016]</a> have recently identified potential additional <i>SYNGAP1</i> <a class="def" href="/books/n/gene/glossary/def-item/isoforms/">isoforms</a> that could arise from alternative <a class="def" href="/books/n/gene/glossary/def-item/splicing/">splicing</a>.</p><p><b>Pathogenic variants.</b> The majority of pathogenic <i>SYNGAP1</i> variants are large deletions or <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> alleles such as <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> and splice variants, frameshift insertions/deletions, and <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions; in addition, pathogenic heterozygous <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants have been reported in a few instances (see review by <a class="bk_pop" href="#syngap1-id.REF.mignot.2016.511">Mignot et al [2016]</a>). Most pathogenic variants occur <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>.</p><p><b>Normal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b> The longest <i>SYNGAP1</i> isoform (NM_006772.2) encodes a protein of 1,343 amino acids that contains pleckstrin homology (PH), C2, RASGAP, SH3-binding, and coiled-coiled domains. Isoform 2 (NM_001130066.1) encodes a protein of 1,292 amino acids that contains the same domains as isoform 1 but has a different C-terminus that includes a QTRV motif required for postsynaptic scaffold protein interaction.</p><p><b>Abnormal <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a>.</b>
|
||
<i>SYNGAP1-</i>ID is caused by <a class="def" href="/books/n/gene/glossary/def-item/haploinsufficiency/">haploinsufficiency</a> of SYNGAP1. Pathogenic variants include those likely to result in complete loss of SYNGAP1 protein expression as well as those predicted to cause truncated or misfolded nonfunctional SYNGAP1.</p></div><div id="syngap1-id.Chapter_Notes"><h2 id="_syngap1-id_Chapter_Notes_">Chapter Notes</h2><div id="syngap1-id.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>21 February 2019 (bp) Review posted live</div></li><li class="half_rhythm"><div>23 October 2017 (jm) Original submission</div></li></ul></div></div><div id="syngap1-id.References"><h2 id="_syngap1-id_References_">References</h2><div id="syngap1-id.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.berryer.2013.385">Berryer MH, Hamdan FF, Klitten LL, Møller RS, Carmant L, Schwartzentruber J, Patry L, Dobrzeniecka S, Rochefort D, Neugnot-Cerioli M, Lacaille JC, Niu Z, Eng CM, Yang Y, Palardy S, Belhumeur C, Rouleau GA, Tommerup N, Immken L, Beauchamp MH, Patel GS, Majewski J, Tarnopolsky MA, Scheffzek K, Hjalgrim H, Michaud JL, Di Cristo G. Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. <span><span class="ref-journal">Hum Mutat. </span>2013;<span class="ref-vol">34</span>:385–94.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23161826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23161826</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.carvill.2013.825">Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. <span><span class="ref-journal">Nat Genet. </span>2013;<span class="ref-vol">45</span>:825–30.</span> [<a href="/pmc/articles/PMC3704157/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3704157</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23708187" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23708187</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.de_ligt.2012.1921">de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, Vulto-van Silfhout AT, Koolen DA, de Vries P, Gilissen C, del Rosario M, Hoischen A, Scheffer H, de Vries BB, Brunner HG, Veltman JA, Vissers LE. Diagnostic exome sequencing in persons with severe intellectual disability. <span><span class="ref-journal">N Engl J Med. </span>2012;<span class="ref-vol">367</span>:1921–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23033978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23033978</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.fitzgerald.2015.223">Fitzgerald TW, Gerety SS, Jones WD, van Kogelenberg M, King DA, McRae J, Morley KI, Parthiban V, Al-Turki S, Ambridge K, Barrett DM, Bayzetinova T, Clayton S, Coomber EL, Gribble S, Jones P, Krishnappa N, Mason LE, et al. 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="syngap1-id.REF.hamdan.2011a.898">Hamdan FF, Daoud H, Piton A, Gauthier J, Dobrzeniecka S, Krebs MO, Joober R, Lacaille JC, Nadeau A, Milunsky JM, Wang Z, Carmant L, Mottron L, Beauchamp MH, Rouleau GA, Michaud JL. De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. <span><span class="ref-journal">Biol Psychiatry. </span>2011a;<span class="ref-vol">69</span>:898–901.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21237447" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21237447</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.hamdan.2011b.306">Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafrenière RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL, et al. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. <span><span class="ref-journal">Am J Hum Genet. </span>2011b;<span class="ref-vol">88</span>:306–16.</span> [<a href="/pmc/articles/PMC3059427/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3059427</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21376300" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21376300</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.hamdan.2009.599">Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, Côté M, Perreau-Linck E, Carmant L, D'Anjou G, Fombonne E, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Mouaffak F, Joober R, Mottron L, Drapeau P, Marineau C, Lafrenière RG, Lacaille JC, Rouleau GA, Michaud JL, et al. Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. <span><span class="ref-journal">N Engl J Med. </span>2009;<span class="ref-vol">360</span>:599–605.</span> [<a href="/pmc/articles/PMC2925262/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2925262</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19196676" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19196676</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.klitten.2011.e190">Klitten LL, Møller RS, Nikanorova M, Silahtaroglu A, Hjalgrim H, Tommerup N. A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA). <span><span class="ref-journal">Epilepsia. </span>2011;<span class="ref-vol">52</span>:e190–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22050443" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22050443</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.krepischi.2010.2376">Krepischi AC, Rosenberg C, Costa SS, Crolla JA, Huang S, Vianna-Morgante AM. A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation. <span><span class="ref-journal">Am J Med Genet A. </span>2010;<span class="ref-vol">152A</span>:2376–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20683986" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20683986</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.mignot.2016.511">Mignot C, von Stülpnagel C, Nava C, Ville D, Sanlaville D, Lesca G, Rastetter A, Gachet B, Marie Y, Korenke GC, Borggraefe I, Hoffmann-Zacharska D, Szczepanik E, Rudzka-Dybała M, Yiş U, Çağlayan H, Isapof A, Marey I, Panagiotakaki E, Korff C, Rossier E, Riess A, Beck-Woedl S, Rauch A, Zweier C, Hoyer J, Reis A, Mironov M, Bobylova M, Mukhin K, Hernandez-Hernandez L, Maher B, Sisodiya S, Kuhn M, Glaeser D, Weckhuysen S, Myers CT, Mefford HC, Hörtnagel K, Biskup S, Lemke JR, Héron D, Kluger G, Depienne C, et al. Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy. <span><span class="ref-journal">J Med Genet. </span>2016;<span class="ref-vol">53</span>:511–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26989088" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26989088</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.parker.2015.2231">Parker MJ, Fryer AE, Shears DJ, Lachlan KL, McKee SA, Magee AC, Mohammed S, Vasudevan PC, Park SM, Benoit V, Lederer D, Maystadt I, Study D, FitzPatrick DR. De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability. <span><span class="ref-journal">Am J Med Genet A. </span>2015;<span class="ref-vol">167A</span>:2231–7.</span> [<a href="/pmc/articles/PMC4744742/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4744742</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26079862" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26079862</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.pinto.2010.368">Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, et al. Functional impact of global rare copy number variation in autism spectrum disorders. <span><span class="ref-journal">Nature. </span>2010;<span class="ref-vol">466</span>:368–72.</span> [<a href="/pmc/articles/PMC3021798/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3021798</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20531469" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20531469</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.prchalova.2017.62">Prchalova D, Havlovicova M, Sterbova K, Stranecky V, Hancarova M, Sedlacek Z. Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype:case report. <span><span class="ref-journal">BMC Med Genet. </span>2017;<span class="ref-vol">18</span>:62.</span> [<a href="/pmc/articles/PMC5457574/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5457574</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28576131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28576131</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.rauch.2012.1674">Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schröck E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. <span><span class="ref-journal">Lancet. </span>2012;<span class="ref-vol">380</span>:1674–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23020937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23020937</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.redin.2014.724">Redin C, Gérard B, Lauer J, Herenger Y, Muller J, Quartier A, Masurel-Paulet A, Willems M, Lesca G, El-Chehadeh S, Le Gras S, Vicaire S, Philipps M, Dumas M, Geoffroy V, Feger C, Haumesser N, Alembik Y, Barth M, Bonneau D, Colin E, Dollfus H, Doray B, Delrue MA, Drouin-Garraud V, Flori E, Fradin M, Francannet C, Goldenberg A, Lumbroso S, Mathieu-Dramard M, Martin-Coignard D, Lacombe D, Morin G, Polge A, Sukno S, Thauvin-Robinet C, Thevenon J, Doco-Fenzy M, Genevieve D, Sarda P, Edery P, Isidor B, Jost B, Olivier-Faivre L, Mandel JL, Piton A. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. <span><span class="ref-journal">J Med Genet. </span>2014;<span class="ref-vol">51</span>:724–36.</span> [<a href="/pmc/articles/PMC4215287/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4215287</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25167861" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25167861</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.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="syngap1-id.REF.vissers.2010.1109">Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, van Lier B, Arts P, Wieskamp N, del Rosario M, van Bon BW, Hoischen A, de Vries BB, Brunner HG, Veltman JA. A de novo paradigm for mental retardation. <span><span class="ref-journal">Nat Genet. </span>2010;<span class="ref-vol">42</span>:1109–12.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21076407" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21076407</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.writzl.2013.1682">Writzl K, Knegt AC. 6p21.3 microdeletion involving the SYNGAP1 gene in a patient with intellectual disability, seizures, and severe speech impairment. <span><span class="ref-journal">Am J Med Genet A. </span>2013;<span class="ref-vol">161A</span>:1682–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23687080" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23687080</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="syngap1-id.REF.zollino.2011.239">Zollino M, Gurrieri F, Orteschi D, Marangi G, Leuzzi V, Neri G. Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndrome. <span><span class="ref-journal">Eur J Hum Genet. </span>2011;<span class="ref-vol">19</span>:239–42.</span> [<a href="/pmc/articles/PMC3025798/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3025798</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21119708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21119708</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: NBK537721</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/30789692" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">30789692</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/syne1ca-ar/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/scs/" 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=NBK537721&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/NBK537721/?report=reader">PubReader</a></li><li><a href="/books/NBK537721/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK537721" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK537721" style="display:none" title="Cite this Page"><div class="bk_tt">Holder JL Jr, Hamdan FF, Michaud JL. SYNGAP1-Related Intellectual Disability. 2019 Feb 21. 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/NBK537721/pdf/Bookshelf_NBK537721.pdf">PDF version of this page</a> (221K)</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="#syngap1-id.Summary" ref="log$=inpage&link_id=inpage">Summary</a></li><li><a href="#syngap1-id.Diagnosis" ref="log$=inpage&link_id=inpage">Diagnosis</a></li><li><a href="#syngap1-id.Clinical_Characteristics" ref="log$=inpage&link_id=inpage">Clinical Characteristics</a></li><li><a href="#syngap1-id.Genetically_Related_Allelic_D" ref="log$=inpage&link_id=inpage">Genetically Related (Allelic) Disorders</a></li><li><a href="#syngap1-id.Differential_Diagnosis" ref="log$=inpage&link_id=inpage">Differential Diagnosis</a></li><li><a href="#syngap1-id.Management" ref="log$=inpage&link_id=inpage">Management</a></li><li><a href="#syngap1-id.Genetic_Counseling" ref="log$=inpage&link_id=inpage">Genetic Counseling</a></li><li><a href="#syngap1-id.Resources" ref="log$=inpage&link_id=inpage">Resources</a></li><li><a href="#syngap1-id.Molecular_Genetics" ref="log$=inpage&link_id=inpage">Molecular Genetics</a></li><li><a href="#syngap1-id.Chapter_Notes" ref="log$=inpage&link_id=inpage">Chapter Notes</a></li><li><a href="#syngap1-id.References" ref="log$=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=8831[geneid]" ref="pagearea=document-links&targetsite=external&targetcat=link&targettype=uri&link_id=tests_in_gtr_by_gene">SYNGAP1</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=4725714" ref="log$=recordlinks">OMIM</a><div class="brieflinkpop offscreen_noflow">Related OMIM records</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=pmc&DbFrom=books&Cmd=Link&LinkName=books_pmc_refs&IdsFromResult=4725714" ref="log$=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=4725714" ref="log$=recordlinks">PubMed</a><div class="brieflinkpop offscreen_noflow">Links to PubMed</div></li><li class="brieflinkpopper"><a class="brieflinkpopperctrl" href="/books/?Db=gene&DbFrom=books&Cmd=Link&LinkName=books_gene&IdsFromResult=4725714" ref="log$=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>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$=activity&linkpos=1" href="/portal/utils/pageresolver.fcgi?recordid=67d2b043b15b832ebc35170e">SYNGAP1-Related Intellectual Disability - GeneReviews®</a><div class="ralinkpop offscreen_noflow">SYNGAP1-Related Intellectual Disability - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=2" href="/portal/utils/pageresolver.fcgi?recordid=67d2b03fa68b6b5afc9bc92a">SYNE1 Deficiency - GeneReviews®</a><div class="ralinkpop offscreen_noflow">SYNE1 Deficiency - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=3" href="/portal/utils/pageresolver.fcgi?recordid=67d2b03db15b832ebc34efbf">SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form wit...</a><div class="ralinkpop offscreen_noflow">SUCLG1-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=4" href="/portal/utils/pageresolver.fcgi?recordid=67d2b039f4a390645e537474">SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form wit...</a><div class="ralinkpop offscreen_noflow">SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li><li class="ra_rcd ralinkpopper two_line"><a class="htb ralinkpopperctrl" ref="log$=activity&linkpos=5" href="/portal/utils/pageresolver.fcgi?recordid=67d2b036f4a390645e5362c6">STXBP1 Encephalopathy with Epilepsy - GeneReviews®</a><div class="ralinkpop offscreen_noflow">STXBP1 Encephalopathy with Epilepsy - GeneReviews®<div class="brieflinkpopdesc"></div></div><div class="tertiary"></div></li></ul><p class="HTOn">Your browsing activity is empty.</p><p class="HTOff">Activity recording is turned off.</p><p id="turnOn" class="HTOff"><a href="javascript:historyDisplayState('HTOn')">Turn recording back on</a></p><a class="seemore" href="/sites/myncbi/recentactivity">See more...</a></div></div></div>
|
||
|
||
<!-- Custom content below discovery portlets -->
|
||
<div class="col7">
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<!-- Custom content after all -->
|
||
<div class="col8">
|
||
|
||
</div>
|
||
<div class="col9">
|
||
|
||
</div>
|
||
|
||
<script type="text/javascript" src="/corehtml/pmc/js/jquery.scrollTo-1.4.2.js"></script>
|
||
<script type="text/javascript">
|
||
(function($){
|
||
$('.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=NBK537721&ncbi_domain=gene&ncbi_report=record&ncbi_type=fulltext&ncbi_objectid=&ncbi_pcid=/NBK537721/&ncbi_pagename=SYNGAP1-Related Intellectual Disability - 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> |