632 lines
103 KiB
Text
632 lines
103 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK1260">
|
|
<meta name="ncbi_domain" content="gene">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK1260/?report=reader">
|
|
<meta name="ncbi_pagename" content="Hereditary Hyperekplexia Overview - GeneReviews® - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Hereditary Hyperekplexia Overview - GeneReviews® - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/gene/hht/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/accpn/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="Hereditary Hyperekplexia Overview">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2019/12/19">
|
|
<meta name="citation_author" content="Bettina Balint">
|
|
<meta name="citation_author" content="Rhys Thomas">
|
|
<meta name="citation_pmid" content="20301437">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1260/">
|
|
<meta name="citation_keywords" content="Glycine receptor subunit alpha-1">
|
|
<meta name="citation_keywords" content="Glycine receptor subunit beta">
|
|
<meta name="citation_keywords" content="Sodium- and chloride-dependent glycine transporter 2">
|
|
<meta name="citation_keywords" content="GLRA1">
|
|
<meta name="citation_keywords" content="GLRB">
|
|
<meta name="citation_keywords" content="SLC6A5">
|
|
<meta name="citation_keywords" content="Hereditary Hyperekplexia">
|
|
<meta name="citation_keywords" content="Overview">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="Hereditary Hyperekplexia Overview">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="Bettina Balint">
|
|
<meta name="DC.Contributor" content="Rhys Thomas">
|
|
<meta name="DC.Date" content="2019/12/19">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1260/">
|
|
<meta name="description" content="The goals of this overview on hereditary hyperekplexia (HPX) caused by dysfunction of glycinergic inhibitory transmission is to:">
|
|
<meta name="og:title" content="Hereditary Hyperekplexia Overview">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="The goals of this overview on hereditary hyperekplexia (HPX) caused by dysfunction of glycinergic inhibitory transmission is to:">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1260/">
|
|
<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/hyperek/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1260/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<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">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<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>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8C80837C86C6710000000000400033.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK1260/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/gene/hht/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Hereditary Hyperekplexia Overview</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/accpn/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK1260/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK1260/&text=Hereditary%20Hyperekplexia%20Overview"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/gene/?report=reader">Title Information</a><a href="/books/n/gene/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK1260/?report=classic">Switch to classic view</a><a href="/books/NBK1260/pdf/Bookshelf_NBK1260.pdf">PDF (458K)</a><a href="/books/NBK1260/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK1260%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8C80837C86C6710000000000400033.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1260_"><span class="title" itemprop="name">Hereditary Hyperekplexia Overview</span></h1><p class="contribs">Balint B, Thomas R.</p><p class="fm-aai"><a href="#_NBK1260_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 18 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="hyperek.Summary" itemprop="description"><h2 id="_hyperek_Summary_">Summary</h2><p>The goals of this overview on hereditary hyperekplexia (HPX) caused by dysfunction of glycinergic inhibitory transmission is to:</p><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><p class="no_top_margin">Describe the <a href="#hyperek.Hereditary_Hyperekplexia_Clinica">clinical characteristics</a> of hereditary hyperekplexia;</p></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><p class="no_top_margin">Review the <a href="#hyperek.Hereditary_Hyperekplexia_Causes">genetic causes</a> of hereditary hyperekplexia;</p></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><p class="no_top_margin">Provide an <a href="#hyperek.Hereditary_Hyperekplexia_Evaluat">evaluation strategy</a> to identify the genetic cause of hereditary hyperekplexia in a proband (when possible);</p></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><p class="no_top_margin">Review <a href="#hyperek.Hereditary_Hyperekplexia_Managem">management</a> of hereditary hyperekplexia;</p></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><p class="no_top_margin">Inform <a href="#hyperek.Hereditary_Hyperekplexia_Genetic">genetic counseling</a> of family members of an individual with hereditary hyperekplexia.</p></dd></dl></dl>
|
|
</div><div id="hyperek.Hereditary_Hyperekplexia_Clinica"><h2 id="_hyperek_Hereditary_Hyperekplexia_Clinica_">1. Hereditary Hyperekplexia: Clinical Characteristics</h2><p>Hereditary hyperekplexia (HPX), an inherited neuronal disorder caused by genetic defects leading to dysfunction of glycinergic inhibitory transmission, is characterized by the clinical core features of exaggerated startle responses to unexpected sensory stimuli and stiffness. HPX, a rare and underdiagnosed disorder, is manifest immediately after birth and commonly improves with age [<a class="bibr" href="#hyperek.REF.paucar.2018.e259" rid="hyperek.REF.paucar.2018.e259">Paucar et la 2018</a>]. Establishing the correct diagnosis early is essential so that proper management may be initiated to alleviate stiffness and reduce the risk of complications, such as potentially life-threatening apnea during episodes of stiffness.</p><p>The term hyperekplexia is used to denote excessive or exaggerated startle that typically does not habituate. Hyperekplexia can be an acquired feature of many disorders, particularly when there is pontine pathology; it may also be observed in infants and children with complex genetic disorders associated with developmental delay/intellectual disability often resulting from an inborn error of metabolism or brain malformation (see <a href="#hyperek.Differential_Diagnosis">Differential Diagnosis</a>).</p><div id="hyperek.HPX_Core_Features"><h3>HPX Core Features</h3><p><b>Excessive startle response</b> (typically eye blinking and a flexor spasm of the trunk) to unexpected, innocuous (particularly auditory) stimuli, the most striking feature of HPX, is present from birth or even noted prenatally in the last trimester [<a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>]. In contrast to a physiologic startle response, the excessive startle leads to prolonged stiffening in the neonate and young infant [<a class="bibr" href="#hyperek.REF.gherpelli.1995.114" rid="hyperek.REF.gherpelli.1995.114">Gherpelli et al 1995</a>, <a class="bibr" href="#hyperek.REF.vergouwe.1997.172" rid="hyperek.REF.vergouwe.1997.172">Vergouwe et al 1997</a>, <a class="bibr" href="#hyperek.REF.koningtijssen.2000.1293" rid="hyperek.REF.koningtijssen.2000.1293">Koning-Tijssen & Brouwer 2000</a>]. Consciousness is unaltered during startle responses, and the responses do not represent epileptic seizures.</p><p>The frequency of startle responses varies considerably among individuals and over time, and often disappears or remits with medication between infancy and adolescence [<a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>].</p><p>Factors that increase the frequency of the startle responses include emotional tension (even the expectation of being frightened), nervousness, and fatigue. Holding objects or drinking alcohol reduces the intensity and frequency of startle responses.</p><p>The exaggerated head-retraction reflex (HRR) is an exaggerated startle response to tactile stimuli and is elicited by gentle taps particularly to the tip of the nose, but also to the nose ridge, the glabella, upper lip, and chin [<a class="bibr" href="#hyperek.REF.wartenberg.1941.553" rid="hyperek.REF.wartenberg.1941.553">Wartenberg 1941</a>]. The reaction is non-habituating and comprises neck extension. Note that HRR is not specific to HPX and has also been described in acquired hyperekplexia and other disorders.</p><p>The excessive startle reflex has major implications for daily life as it cannot be suppressed and unexpected stimuli from the outside world cannot be regulated. This is a prominent problem for some infants when the simple activities of feeding or being dressed produce paroxysms of startle responses. In later life, the excessive startle reflex and associated generalized stiffness increase the risk of falls and injury.</p><p><b>Stiffness.</b> The two main types of stiffness in relation to HPX are generalized continuous stiffness from birth on and stiffness induced by startle that may persist into adulthood.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Generalized stiffness apparent immediately after birth.</b> The stiffness increases with handling and disappears during sleep. Held horizontally, the baby is as "stiff as a stick" – therefore, the disorder is also called stiff-baby syndrome. The baby is alert but shows few spontaneous movements [<a class="bibr" href="#hyperek.REF.koningtijssen.2000.1293" rid="hyperek.REF.koningtijssen.2000.1293">Koning-Tijssen & Brouwer 2000</a>]. Handling a baby, for example when changing diapers, is difficult because spreading of the legs is limited by stiffness.</div><div class="half_rhythm">The generalized stiffness evident immediately after birth usually normalizes during the first years of life (by age 2 years; range: 0.7-5 years) [<a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Generalized stiffness following the startle response</b> means that for a short period, affected individuals become stiff and voluntary movements are impossible [<a class="bibr" href="#hyperek.REF.bernasconi.1996.447" rid="hyperek.REF.bernasconi.1996.447">Bernasconi et al 1996</a>]. Startled individuals may fall "like a log," with the stiffness preventing them from putting out their arms to safeguard themselves, resulting in an increased risk of injuries [<a class="bibr" href="#hyperek.REF.tijssen.2002.826" rid="hyperek.REF.tijssen.2002.826">Tijssen et al 2002</a>, <a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>, <a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>, <a class="bibr" href="#hyperek.REF.lee.2017.53" rid="hyperek.REF.lee.2017.53">Lee et al 2017</a>]. This may persist into adult life. Affected individuals may have a cautious, stiff-legged, broad-based gait (but without signs of ataxia; see video at <a class="bibr" href="#hyperek.REF.zhang.2019.e2068" rid="hyperek.REF.zhang.2019.e2068">Zhang et al [2019]</a>; <a href="https://n.neurology.org/content/92/17/e2068.long" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>).</div></li></ul><p>Other complications of severe attacks of stiffness:</p><ul><li class="half_rhythm"><div>Episodes of tonic neonatal cyanosis (i.e., attacks of apnea in neonates with HPX) [<a class="bibr" href="#hyperek.REF.vergouwe.1997.172" rid="hyperek.REF.vergouwe.1997.172">Vergouwe et al 1997</a>, <a class="bibr" href="#hyperek.REF.miraglia_del_giudice.2003.e71" rid="hyperek.REF.miraglia_del_giudice.2003.e71">Miraglia Del Giudice et al 2003</a>, <a class="bibr" href="#hyperek.REF.rees.2006.801" rid="hyperek.REF.rees.2006.801">Rees et al 2006</a>, <a class="bibr" href="#hyperek.REF.rivera.2006.104" rid="hyperek.REF.rivera.2006.104">Rivera et al 2006</a>]. Akin to the generalized stiffness, attacks of tonic neonatal cyanosis often resolve during infancy [<a class="bibr" href="#hyperek.REF.rees.2006.801" rid="hyperek.REF.rees.2006.801">Rees et al 2006</a>]. The association with sudden infant death syndrome underlines the importance of early diagnosis and treatment [<a class="bibr" href="#hyperek.REF.nigro.1992.221" rid="hyperek.REF.nigro.1992.221">Nigro & Lim 1992</a>].</div></li><li class="half_rhythm"><div>Frequent occurrence of inguinal, umbilical, or epigastric hernias, paralytic ileus, and congenital dislocation of the hip [<a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>]</div></li></ul><p><b>Associated features</b> that may be present include the following:</p><ul><li class="half_rhythm"><div>In some children, delayed motor milestones and mild developmental delay or learning difficulties (particularly speech acquisition); children later catch up [<a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>].</div></li><li class="half_rhythm"><div>Periodic limb movements in sleep (PLMS) and hypnagogic myoclonus (myoclonus occurring when falling asleep)</div></li><li class="half_rhythm"><div>Epilepsy; estimated prevalence in hyperekplexia of 7%-12% [<a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>]</div></li></ul></div><div id="hyperek.Differential_Diagnosis"><h3>Differential Diagnosis</h3><p>The differential diagnosis of abnormal startle can be divided into the following:</p><ul><li class="half_rhythm"><div class="half_rhythm"><a href="#hyperek.Conditions_with_an_Abnormal_Exag">Conditions with an abnormal, exaggerated startle</a> including:</div><ul><li class="half_rhythm"><div>Complex genetic neurodevelopmental disorders</div></li><li class="half_rhythm"><div>Acquired causes</div></li></ul><div class="half_rhythm">Note: It is this group of disorders that is most likely to be confused with hereditary hyperekplexia resulting from dysfunction of glycinergic inhibitory transmission.</div></li><li class="half_rhythm"><div class="half_rhythm"><a href="#hyperek.StartleInduced_Manifestations_in">Conditions in which the startle response per se is normal</a>, but the startle is triggering the actual disease-defining symptoms</div></li><li class="half_rhythm"><div class="half_rhythm"><a href="#hyperek.Neuropsychiatric_Startle_Syndrom">Neuropsychiatric syndromes</a>, in which startle may be excessive and can be followed by additional manifestations</div></li></ul><div id="hyperek.Conditions_with_an_Abnormal_Exag"><h4>Conditions with an Abnormal, Exaggerated Startle</h4><p><b>Complex genetic neurodevelopmental disorders</b> in which an excessive startle response in infants and children can be associated with developmental delay/intellectual disability often resulting from an inborn error of metabolism or brain malformation (with or without microcephaly and/or epilepsy) (<a href="/books/NBK1260/table/hyperek.T.complex_genetic_neurodevelopme/?report=objectonly" target="object" rid-ob="figobhyperekTcomplexgeneticneurodevelopme">Table 1</a>) are distinct from hereditary hyperekplexia and will not be discussed further in this overview.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighyperekTcomplexgeneticneurodevelopme"><a href="/books/NBK1260/table/hyperek.T.complex_genetic_neurodevelopme/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobhyperekTcomplexgeneticneurodevelopme"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hyperek.T.complex_genetic_neurodevelopme"><a href="/books/NBK1260/table/hyperek.T.complex_genetic_neurodevelopme/?report=objectonly" target="object" rid-ob="figobhyperekTcomplexgeneticneurodevelopme">Table 1. </a></h4><p class="float-caption no_bottom_margin">Complex Genetic Neurodevelopmental Disorders with an Excessive Startle Response </p></div></div><p>
|
|
<b>Acquired causes of excessive startle</b>
|
|
</p><ul><li class="half_rhythm"><div><b>Structural and other causes of brain stem dysfunction</b> can include post-anoxic reticular myoclonus, infarct, hemorrhage, medullary compression, posterior fossa malformations, neurodegeneration (multisystem atrophy, lateral sclerosis), and infectious or autoimmune encephalitis (reviewed in <a class="bibr" href="#hyperek.REF.balint.2018.13" rid="hyperek.REF.balint.2018.13">Balint et al [2018]</a>) including multiple sclerosis [<a class="bibr" href="#hyperek.REF.abboud.2019.24" rid="hyperek.REF.abboud.2019.24">Abboud et al 2019</a>].</div></li><li class="half_rhythm"><div><b>Infection.</b> The most important infectious cause is tetanus, a potentially lethal disorder caused by the toxin of <i>Clostridium tetani</i> which degrades synaptobrevin and thereby prevents neurotransmitter release for glycinergic inhibition. The latter is the common end route with HPX, explaining the phenotypic similarities.</div></li><li class="half_rhythm"><div><b>Glycine receptor antibodies</b> (targeting the same protein affected by pathogenic variants in <i>GLRA</i>) are an autoimmune cause of exaggerated startle and stiffness [<a class="bibr" href="#hyperek.REF.hutchinson.2008.1291" rid="hyperek.REF.hutchinson.2008.1291">Hutchinson et al 2008</a>] and may manifest as brain stem encephalitis or a variant of stiff person spectrum disorder (SPSD), such as progressive encephalomyelitis with rigidity and myoclonus [<a class="bibr" href="#hyperek.REF.balint.2016.496" rid="hyperek.REF.balint.2016.496">Balint & Bhatia 2016</a>]. However, SPSD is also seen with glutamic acid decarboxylase, amphiphysin, or DPPX antibodies. They share as core features stiffness, spasms, and hyperekplexia (in varying degrees and body distribution). Onset is typically in adulthood, although infantile onset has been described by <a class="bibr" href="#hyperek.REF.dam_sio.2013.498" rid="hyperek.REF.dam_sio.2013.498">Damásio et al [2013]</a>. Other features distinguishing SPSD from HPX are the mostly continuous and prominent muscle stiffness, sometimes co-occurring neurologic signs, and often a strong association with other autoimmune diseases.</div></li><li class="half_rhythm"><div><b>Strychnine</b> is a competitive inhibitor of the postsynaptic glycine receptor. Strychnine poisoning causes acute onset of stiffness, spasms, and hyperekplexia.</div></li></ul></div><div id="hyperek.StartleInduced_Manifestations_in"><h4>Startle-Induced Manifestations in Other Disorders</h4><p>In this diverse group of disorders, the startle reflex itself is not excessive, but rather induces another clinical feature that is more prominent and characteristic than the startle response [<a class="bibr" href="#hyperek.REF.dreissen.2012.3" rid="hyperek.REF.dreissen.2012.3">Dreissen & Tijssen 2012</a>]. Examples include the following:</p><ul><li class="half_rhythm"><div>Startle epilepsy (normal startle triggers seizures)</div></li><li class="half_rhythm"><div>Paroxysmal kinesigenic choreoathetosis (See <a href="/books/n/gene/prrt2-parox/?report=reader"><i>PRRT2</i>-Associated Paroxysmal Movement Disorders</a>; startle can be one of many triggers of sudden movements.)</div></li><li class="half_rhythm"><div>Creutzfeldt-Jakob disease (See <a href="/books/n/gene/prion/?report=reader">Genetic Prion Disease</a>.)</div></li><li class="half_rhythm"><div>Subacute sclerosing panencephalitis</div></li></ul></div><div id="hyperek.Neuropsychiatric_Startle_Syndrom"><h4>Neuropsychiatric Startle Syndromes</h4><p>In addition to excessive startling, behavioral and/or psychiatric findings are observed in the following groups of disorders:</p><ul><li class="half_rhythm"><div>Culture-specific syndromes, in which an exaggerated startle response, evoked by auditory, sensory, or visual stimuli occurs within a community [<a class="bibr" href="#hyperek.REF.meinck.2006.357" rid="hyperek.REF.meinck.2006.357">Meinck 2006</a>]. The initial brief component of the startle reflex is normal, but the secondary orientating response includes abnormal behaviors such as jumps, echopraxia, or echolalia, spontaneous vocalizations including coprolalia, and automatic execution when startled with vigorous commands ("forced obedience").</div></li><li class="half_rhythm"><div>Anxiety disorders, functional neurologic disorders</div></li><li class="half_rhythm"><div>Tics and Gilles de la Tourette syndrome, in which an exaggerated startle reflex has been described in some, but not all, affected individuals</div></li></ul></div></div></div><div id="hyperek.Hereditary_Hyperekplexia_Causes"><h2 id="_hyperek_Hereditary_Hyperekplexia_Causes_">2. Hereditary Hyperekplexia: Causes</h2><p>To date, three genes are known to be associated with hereditary hyperekplexia (HPX): <i>GLRA1</i>, <i>GLRB</i>, and <i>SLC6A5</i>. Genetic defects in these genes result in dysfunction of glycinergic inhibitory transmission. The relative contribution of each of these three genes to HPX (based on data on 97 individuals with confirmed <i>GLRA1</i>-, <i>GLRB</i>-, or <i>SLC6A5</i>-HPX [<a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>]), the modes of inheritance, and methods of pathogenic variant detection are summarized in <a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="fighyperekTglra1glrbandslc6a5relatedh"><a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="hyperek.T.glra1_glrb_and_slc6a5related_h"><a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>GLRA1</i>, <i>GLRB</i>, and <i>SLC6A5</i>-Related Hereditary Hyperekplexia: Modes of Inheritance and Methods of Variant Detection </p></div></div><div id="hyperek.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><p>The following were observed in the study of <a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al [2013]</a>:</p><ul><li class="half_rhythm"><div>Individuals with <i>GLRB</i>-HPX or <i>SLC6A5</i>-HPX were more likely to have developmental delay (RR1.5 P<0.01; RR1.9 P<0.03) than those with <i>GLRA1</i>-HPX, whereas 92% of individuals reported with <i>GLRB</i>-HPX had mild-to-severe delay in speech acquisition.</div></li><li class="half_rhythm"><div>Children with <i>SLC6A5-</i>HPX were significantly more likely to have had recurrent infantile apnea (RR1.9; P<0.005) than those with <i>GLRA1</i>-HPX.</div></li><li class="half_rhythm"><div>Individuals without a molecularly confirmed diagnosis of HPX compared to those with a molecular diagnosis were more likely to have first clinical manifestations after age one month (P<0.001). In contrast, the characteristic "stiffness, startles, and stumbles" of hyperekplexia, apnea attacks (50 of 89), and delayed development (47 of 92) were frequently reported in both groups.</div></li><li class="half_rhythm"><div>Individuals with a molecularly confirmed diagnosis of HPX typically are not dysmorphic and brain imaging reveals a structurally normal brain.</div></li></ul></div></div><div id="hyperek.Hereditary_Hyperekplexia_Evaluat"><h2 id="_hyperek_Hereditary_Hyperekplexia_Evaluat_">3. Hereditary Hyperekplexia: Evaluation Strategy to Identify the Genetic Cause in a Proband</h2><p>Establishing a specific genetic cause of HPX can aid genetic counseling (see <a href="#hyperek.Hereditary_Hyperekplexia_Genetic">Section 5</a>). Establishing the genetic cause of HPX in a proband usually involves family history and genomic/genetic testing.</p><p><b>Family history.</b> A three-generation family history should be obtained, with attention to relatives with HPX and documentation of relevant findings through direct examination or review of medical records including results of molecular genetic testing. Identify "sudden infant deaths" that may have been caused by apnea.</p><p><b>Molecular genetic testing</b> approaches can include a combination of gene-targeted testing (multigene panel or single-gene testing) and comprehensive genomic testing (exome sequencing, exome array, or chromosomal microarray analysis [CMA]). Some pathogenic variants are more common in some geographic regions and population groups [<a class="bibr" href="#hyperek.REF.thomas.2015.341" rid="hyperek.REF.thomas.2015.341">Thomas et al 2015</a>]. Gene-targeted testing requires the clinician to hypothesize which gene(s) are likely involved, whereas genomic testing does not.</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Serial single-gene testing</b> can be considered if family history indicates that pathogenic variants in a particular gene are most likely (see <a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh">Table 2</a>). Sequence analysis detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. Perform sequence analysis in the following order: <i>GLRA1</i>, <i>SLC6A5</i>, and <i>GLRB</i>. If no pathogenic variant is found, perform gene-targeted deletion/duplication analysis to detect intragenic deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A multigene panel</b> that includes <i>GLRA1</i>, <i>GLRB</i>, and <i>SLC6A5</i> is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene 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 exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For this disorder a multigene panel that also includes deletion/duplication analysis is recommended (see <a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh">Table 2</a>).</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Comprehensive</b>
|
|
<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible. If exome sequencing is not diagnostic, <b>exome array</b> (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis.</div><div class="half_rhythm">For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul></div><div id="hyperek.Hereditary_Hyperekplexia_Managem"><h2 id="_hyperek_Hereditary_Hyperekplexia_Managem_">4. Hereditary Hyperekplexia: Management</h2><div id="hyperek.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Clonazepam is the treatment of choice for HPX [<a class="bibr" href="#hyperek.REF.tijssen.1997.63" rid="hyperek.REF.tijssen.1997.63">Tijssen et al 1997</a>, <a class="bibr" href="#hyperek.REF.tsai.2004.893" rid="hyperek.REF.tsai.2004.893">Tsai et al 2004</a>, <a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>, <a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>]. The stiffness in the neonatal period and stiffness related to startle diminish with the treatment. Suggested daily doses are 0.01 to 0.1 mg/kg for children and 0.8 mg/d for adults [<a class="bibr" href="#hyperek.REF.mine.2015.372" rid="hyperek.REF.mine.2015.372">Mine et al 2015</a>].</p><p>Other drugs, mostly described in case reports, which have shown variable results include: carbamazepine, clobazam, phenytoin, diazepam, valproate, 5-hydroxytryptophan, piracetam, and phenobarbital. For an overview see <a class="bibr" href="#hyperek.REF.bakker.2006.513" rid="hyperek.REF.bakker.2006.513">Bakker et al [2006]</a>.</p><p>Physical and cognitive therapy to reduce the fear of falling and thereby improve walking can be considered; no randomized trials have assessed the effectiveness of such treatment.</p><p>Attacks of tonic neonatal cyanosis can be stopped by the Vigevano maneuver, consisting of forced flexion of the head and legs towards the trunk [<a class="bibr" href="#hyperek.REF.vigevano.1989.216" rid="hyperek.REF.vigevano.1989.216">Vigevano et al 1989</a>].</p></div></div><div id="hyperek.Hereditary_Hyperekplexia_Genetic"><h2 id="_hyperek_Hereditary_Hyperekplexia_Genetic_">5. Hereditary Hyperekplexia: 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="hyperek.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>GLRA1</i>- and <i>GLRB-</i>related hereditary hyperekplexia (HPX) can be inherited in an autosomal recessive or, less commonly, an autosomal dominant manner (<a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object" rid-ob="figobhyperekTglra1glrbandslc6a5relatedh">Table 2</a>). <i>SLC6A5</i>-HPX is inherited in an autosomal recessive manner (autosomal dominant inheritance of <i>SLC6A5</i>-HPX has been reported in one family). General genetic counseling issues regarding autosomal dominant and recessive inheritance are discussed in this section.</p></div><div id="hyperek.Autosomal_Recessive_Inheritance"><h3>Autosomal Recessive Inheritance – Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The parents of a child with autosomal recessive HPX are obligate heterozygotes (i.e., presumed to be carriers of one <i>GLRA1</i>, <i>GLRB</i>, or <i>SLC6A5</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an autosomal recessive HPX-causing pathogenic variant and to allow reliable recurrence risk assessment. (<i>De novo</i> variants are known to occur at a low but appreciable rate in autosomal recessive disorders [<a class="bibr" href="#hyperek.REF.j_nsson.2017.519" rid="hyperek.REF.j_nsson.2017.519">Jónsson et al 2017</a>].)</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing hyperekplexia.</div></li></ul><p>
|
|
<b>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an autosomal recessive HPX-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with autosomal recessive HPX are obligate heterozygotes (carriers) for a pathogenic variant.</p><p><b>Carrier detection.</b> Carrier testing for at-risk relatives requires prior identification of the pathogenic variants in the family.</p></div><div id="hyperek.Autosomal_Dominant_Inheritance"><h3>Autosomal Dominant Inheritance – Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>Most individuals diagnosed with autosomal dominant HPX have an affected parent.</div></li><li class="half_rhythm"><div>In rare cases, an individual diagnosed with autosomal dominant HPX has the disorder as the result of a <i>de novo GLRA1</i> or <i>GLRB</i> pathogenic variant [<a class="bibr" href="#hyperek.REF.miraglia_del_giudice.2003.e71" rid="hyperek.REF.miraglia_del_giudice.2003.e71">Miraglia Del Giudice et al 2003</a>, <a class="bibr" href="#hyperek.REF.james.2013.137" rid="hyperek.REF.james.2013.137">James et al 2013</a>, <a class="bibr" href="#hyperek.REF.horv_th.2014.233" rid="hyperek.REF.horv_th.2014.233">Horváth et al 2014</a>].</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband with an apparent <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in leukocyte DNA of either parent, the proband most likely has a <i>de novo</i> pathogenic variant; another possible explanation is germline mosaicism in a parent (though theoretically possible, no instances of parental germline mosaicism have been reported).</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs of having the same pathogenic variant is 50%. However, because autosomal dominant hereditary hyperekplexia is not 100% penetrant, sibs who inherit a pathogenic variant may or may not manifest features of HPX [<a class="bibr" href="#hyperek.REF.sprovieri.2019.40" rid="hyperek.REF.sprovieri.2019.40">Sprovieri et al 2019</a>].</div></li><li class="half_rhythm"><div>If the proband has a known pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism [<a class="bibr" href="#hyperek.REF.rahbari.2016.126" rid="hyperek.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for hereditary hyperekplexia because of the possibility of reduced penetrance in a heterozygous parent or the theoretic possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with autosomal dominant HPX has a 50% chance of inheriting the pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent is affected, the parent's family members may be at risk.</p></div><div id="hyperek.Prenatal_Testing_and_Preimplanta"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the HPX-causing pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="hyperek.Resources"><h2 id="_hyperek_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/?report=reader">here</a>.</i></p>
|
|
<ul><li class="half_rhythm"><div>
|
|
<b>National Library of Medicine Genetics Home Reference</b>
|
|
</div><div>
|
|
<a href="http://ghr.nlm.nih.gov/condition/hereditary-hyperekplexia" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Hereditary hyperekplexia</a>
|
|
</div></li></ul>
|
|
</div><div id="hyperek.Chapter_Notes"><h2 id="_hyperek_Chapter_Notes_">Chapter Notes</h2><div id="hyperek.Author_History"><h3>Author History</h3><p>Bettina Balint, MD (2019-present)<br />Mark I Rees, PhD; Swansea University (2007-2019)<br />Rhys Thomas, PhD, FRCP (2019-present)<br />Marina AJ Tijssen, MD; University Medical Center Groningen (2007-2019)</p></div><div id="hyperek.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>19 December 2019 (bp) Comprehensive update posted live; scope changed to overview</div></li><li class="half_rhythm"><div>4 October 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>31 July 2007 (me) Review posted live</div></li><li class="half_rhythm"><div>6 July 2006 (sgr) Original submission</div></li></ul></div></div><div id="hyperek.References"><h2 id="_hyperek_References_">References</h2><div id="hyperek.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.abboud.2019.24">Abboud
|
|
H, Yu
|
|
XX, Knusel
|
|
K, Fernandez
|
|
HH, Cohen
|
|
JA. Movement disorders in early MS and related diseases: A prospective observational study.
|
|
Neurol Clin Pract.
|
|
2019;9:24–31.
|
|
[<a href="/pmc/articles/PMC6382384/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6382384</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30859004" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30859004</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.bakker.2006.513">Bakker
|
|
MJ, van Dijk
|
|
JG, van den Maagdenberg
|
|
AM, Tijssen
|
|
MA. Startle syndromes.
|
|
Lancet Neurol.
|
|
2006;5:513–24.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16713923" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16713923</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.balint.2016.496">Balint
|
|
B, Bhatia
|
|
KP. Stiff person syndrome and other immune-mediated movement disorders - new insights.
|
|
Curr Opin Neurol.
|
|
2016;29:496–506.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27262149" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27262149</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.balint.2018.13">Balint
|
|
B, Vincent
|
|
A, Meinck
|
|
HM, Irani
|
|
SR, Bhatia
|
|
KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology.
|
|
Brain.
|
|
2018;141:13–36.
|
|
[<a href="/pmc/articles/PMC5888977/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5888977</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29053777" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29053777</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.bernasconi.1996.447">Bernasconi
|
|
A, Regli
|
|
F, Schorderet
|
|
DF, Pescia
|
|
G. Familial hyperekplexia: startle disease. Clinical, electrophysiological and genetic study of a family.
|
|
Rev Neurol (Paris). 1996;152:447–50.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/8944241" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8944241</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.brune.1996.989">Brune
|
|
W, Weber
|
|
RG, Saul
|
|
B, von Knebel Doeberitz
|
|
M, Grond-Ginsbach
|
|
C, Kellerman
|
|
K, Meinck
|
|
HM, Becker
|
|
CM. A.
|
|
GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors.
|
|
Am J Hum Genet.
|
|
1996;58:989–97.
|
|
[<a href="/pmc/articles/PMC1914607/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1914607</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8651283" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8651283</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.chung.2013.927">Chung
|
|
SK, Bode
|
|
A, Cushion
|
|
TD, Thomas
|
|
RH, Hunt
|
|
C, Wood
|
|
SE, Pickrell
|
|
WO, Drew
|
|
CJ, Yamashita
|
|
S, Shiang
|
|
R, Leiz
|
|
S, Longardt
|
|
AC, Raile
|
|
V, Weschke
|
|
B, Puri
|
|
RD, Verma
|
|
IC, Harvey
|
|
RJ, Ratnasinghe
|
|
DD, Parker
|
|
M, Rittey
|
|
C, Masri
|
|
A, Lingappa
|
|
L, Howell
|
|
OW, Vanbellinghen
|
|
JF, Mullins
|
|
JG, Lynch
|
|
JW, Rees
|
|
MI. GLRB is the third major gene of effect in hyperekplexia.
|
|
Hum Mol Genet.
|
|
2013;22:927–40.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23184146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23184146</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.chung.2010.9612">Chung
|
|
SK, Vanbellinghen
|
|
JF, Mullins
|
|
JG, Robinson
|
|
A, Hantke
|
|
J, Hammond
|
|
CL, Gilbert
|
|
DF, Freilinger
|
|
M, Ryan
|
|
M, Kruer
|
|
MC, Masri
|
|
A, Gurses
|
|
C, Ferrie
|
|
C, Harvey
|
|
K, Shiang
|
|
R, Christodoulou
|
|
J, Andermann
|
|
F, Andermann
|
|
E, Thomas
|
|
RH, Harvey
|
|
RJ, Lynch
|
|
JW, Rees
|
|
MI. Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia.
|
|
J Neurosci.
|
|
2010;30:9612–20.
|
|
[<a href="/pmc/articles/PMC6632444/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6632444</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20631190" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20631190</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.dam_sio.2013.498">Damásio
|
|
J, Leite
|
|
MI, Coutinho
|
|
E, Waters
|
|
P, Woodhall
|
|
M, Santos
|
|
MA, Carrilho
|
|
I, Vincent
|
|
A. Progressive encephalomyelitis with rigidity and myoclonus: the first pediatric case with glycine receptor antibodies.
|
|
JAMA Neurol.
|
|
2013;70:498–501.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23380884" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23380884</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.dreissen.2012.3">Dreissen
|
|
YE, Tijssen
|
|
MA. The startle syndromes: physiology and treatment.
|
|
Epilepsia.
|
|
2012;53
|
|
Suppl 7:3–11.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23153204" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23153204</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.gherpelli.1995.114">Gherpelli
|
|
JL, Nogueira
|
|
AR
|
|
Jr, Troster
|
|
EJ, Deutsch
|
|
AD, Leone
|
|
CR, Brotto
|
|
MW, Diament
|
|
A, Ramos
|
|
JL. Hyperekplexia, a cause of neonatal apnea: a case report.
|
|
Brain Dev.
|
|
1995;17:114–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/7625544" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7625544</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.horv_th.2014.233">Horváth
|
|
E, Farkas
|
|
K, Herczegfalvi
|
|
A, Nagy
|
|
N, Széll
|
|
M. Identification of a novel missense GLRA1 gene mutation in hyperekplexia: a case report.
|
|
J Med Case Rep.
|
|
2014;8:233.
|
|
[<a href="/pmc/articles/PMC4096538/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4096538</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24969041" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24969041</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.hutchinson.2008.1291">Hutchinson
|
|
M, Waters
|
|
P, McHugh
|
|
J, Gorman
|
|
G, O'Riordan
|
|
S, Connolly
|
|
S, Hager
|
|
H, Yu
|
|
P, Becker
|
|
CM, Vincent
|
|
A. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody.
|
|
Neurology.
|
|
2008;71:1291–2.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18852446" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18852446</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.james.2013.137">James
|
|
VM, Bode
|
|
A, Chung
|
|
SK, Gill
|
|
JL, Nielsen
|
|
M, Cowan
|
|
FM, Vujic
|
|
M, Thomas
|
|
RH, Rees
|
|
MI, Harvey
|
|
K, Keramidas
|
|
A, Topf
|
|
M, Ginjaar
|
|
I, Lynch
|
|
JW, Harvey
|
|
RJ. Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease.
|
|
Neurobiol Dis.
|
|
2013;52:137–49.
|
|
[<a href="/pmc/articles/PMC3581774/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3581774</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23238346" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23238346</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.j_nsson.2017.519">Jónsson
|
|
H, Sulem
|
|
P, Kehr
|
|
B, Kristmundsdottir
|
|
S, Zink
|
|
F, Hjartarson
|
|
E, Hardarson
|
|
MT, Hjorleifsson
|
|
KE, Eggertsson
|
|
HP, Gudjonsson
|
|
SA, Ward
|
|
LD, Arnadottir
|
|
GA, Helgason
|
|
EA, Helgason
|
|
H, Gylfason
|
|
A, Jonasdottir
|
|
A, Jonasdottir
|
|
A, Rafnar
|
|
T, Frigge
|
|
M, Stacey
|
|
SN, Th Magnusson
|
|
O, Thorsteinsdottir
|
|
U, Masson
|
|
G, Kong
|
|
A, Halldorsson
|
|
BV, Helgason
|
|
A, Gudbjartsson
|
|
DF, Stefansson
|
|
K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland.
|
|
Nature.
|
|
2017;549:519–22.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.koningtijssen.2000.1293">Koning-Tijssen
|
|
MA, Brouwer
|
|
OF. Hyperekplexia in the first year of life.
|
|
Mov Disord.
|
|
2000;15:1293–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11104232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11104232</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.lee.2017.53">Lee
|
|
Y, Kim
|
|
NY, Hong
|
|
S, Chung
|
|
SJ, Jeong
|
|
SH, Lee
|
|
PH, Sohn
|
|
YH. Familiar hyperekplexia, a potential cause of cautious gait: a new Korean case and a systematic review of phenotypes.
|
|
J Mov Disord.
|
|
2017;10:53–8.
|
|
[<a href="/pmc/articles/PMC5288664/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5288664</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28122427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28122427</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.meinck.2006.357">Meinck
|
|
HM. Startle and its disorders.
|
|
Neurophysiol Clin.
|
|
2006;36:357–64.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17336782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17336782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.mine.2015.372">Mine
|
|
J, Taketani
|
|
T, Yoshida
|
|
K, Yokochi
|
|
F, Kobayashi
|
|
J, Maruyama
|
|
K, Nanishi
|
|
E, Ono
|
|
M, Yokoyama
|
|
A, Arai
|
|
H, Tamaura
|
|
S, Suzuki
|
|
Y, Otsubo
|
|
S, Hayashi
|
|
T, Kimura
|
|
M, Kishi
|
|
K, Yamaguchi
|
|
S.
|
|
Clinical and genetic investigation of 17 Japanese patients with hyperekplexia.
|
|
Dev Med Child Neurol.
|
|
2015;57:372–7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25356525" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25356525</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.miraglia_del_giudice.2003.e71">Miraglia Del Giudice
|
|
E, Coppola
|
|
G, Bellini
|
|
G, Ledaal
|
|
P, Hertz
|
|
JM, Pascotto
|
|
A. A novel mutation (R218Q) at the boundary between the N-terminal and the first transmembrane domain of the glycine receptor in a case of sporadic hyperekplexia.
|
|
J Med Genet.
|
|
2003;40:e71.
|
|
[<a href="/pmc/articles/PMC1735464/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735464</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12746425" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12746425</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.nigro.1992.221">Nigro
|
|
MA, Lim
|
|
HC. Hyperekplexia and sudden neonatal death.
|
|
Pediatr Neurol.
|
|
1992;8:221–5.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/1622521" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1622521</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.paucar.2018.e259">Paucar
|
|
M, Waldthaler
|
|
J, Svenningsson
|
|
P.
|
|
GLRA1 mutation and long-term follow-up of the first hyperekplexia family.
|
|
Neurol Genet.
|
|
2018;4:e259.
|
|
[<a href="/pmc/articles/PMC6089692/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6089692</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30109271" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30109271</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.rahbari.2016.126">Rahbari
|
|
R, Wuster
|
|
A, Lindsay
|
|
SJ, Hardwick
|
|
RJ, Alexandrov
|
|
LB, Turki
|
|
SA, Dominiczak
|
|
A, Morris
|
|
A, Porteous
|
|
D, Smith
|
|
B, Stratton
|
|
MR. UK10K Consortium, Hurles ME. Timing, rates and spectra of human germline mutation.
|
|
Nat Genet.
|
|
2016;48:126–33.
|
|
[<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.rees.2006.801">Rees
|
|
MI, Harvey
|
|
K, Pearce
|
|
BR, Chung
|
|
SK, Duguid
|
|
IC, Thomas
|
|
P, Beatty
|
|
S, Graham
|
|
GE, Armstrong
|
|
L, Shiang
|
|
R, Abbott
|
|
KJ, Zuberi
|
|
SM, Stephenson
|
|
JB, Owen
|
|
MJ, Tijssen
|
|
MA, van den Maagdenberg
|
|
AM, Smart
|
|
TG, Supplisson
|
|
S, Harvey
|
|
RJ. Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease.
|
|
Nat Genet.
|
|
2006;38:801–6.
|
|
[<a href="/pmc/articles/PMC3204411/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3204411</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16751771" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16751771</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.rivera.2006.104">Rivera
|
|
S, Villega
|
|
F, de Saint-Martin
|
|
A, Matis
|
|
J, Escande
|
|
B, Chaigne
|
|
D, Astruc
|
|
D.
|
|
Congenital hyperekplexia: five sporadic cases.
|
|
Eur J Pediatr.
|
|
2006;165:104–7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16211400" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16211400</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.sprovieri.2019.40">Sprovieri
|
|
T, Ungaro
|
|
C, Sivo
|
|
S, Quintiliani
|
|
M, Contaldo
|
|
I, Veredice
|
|
C, Citrigno
|
|
L, Muglia
|
|
M, Cavalcanti
|
|
F, Cavallaro
|
|
S, Mercuri
|
|
E, Battaglia
|
|
D. Clinical features and genetic analysis of two siblings with startle disease in an Italian family: a case report.
|
|
BMC Med Genet.
|
|
2019;20:40.
|
|
[<a href="/pmc/articles/PMC6417078/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6417078</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30866851" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30866851</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.stenson.2020.1197">Stenson
|
|
PD, Mort
|
|
M, Ball
|
|
EV, Chapman
|
|
M, Evans
|
|
K, Azevedo
|
|
L, Hayden
|
|
M, Heywood
|
|
S, Millar
|
|
DS, Phillips
|
|
AD, Cooper
|
|
DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting.
|
|
Hum Genet.
|
|
2020;139:1197–207.
|
|
[<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.thomas.2013.3085">Thomas
|
|
RH, Chung
|
|
SK, Wood
|
|
SE, Cushion
|
|
TD, Drew
|
|
CJ, Hammond
|
|
CL, Vanbellinghen
|
|
JF, Mullins
|
|
JG, Rees
|
|
MI. Genotype-phenotype correlations in hyperekplexia: apnoeas, learning difficulties and speech delay.
|
|
Brain.
|
|
2013;136:3085–95.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24030948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24030948</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.thomas.2015.341">Thomas
|
|
RH, Drew
|
|
CJ, Wood
|
|
SE, Hammond
|
|
CL, Chung
|
|
SK, Rees
|
|
MI. Ethnicity can predict GLRA1 genotypes in hyperekplexia.
|
|
J Neurol Neurosurg Psychiatry.
|
|
2015;86:341–3.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24970905" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24970905</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.tijssen.1997.63">Tijssen
|
|
MA, Schoemaker
|
|
HC, Edelbroek
|
|
PJ, Roos
|
|
RA, Cohen
|
|
AF, van Dijk
|
|
JG. The effects of clonazepam and vigabatrin in hyperekplexia.
|
|
J Neurol Sci.
|
|
1997;149:63–7.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9168167" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9168167</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.tijssen.2002.826">Tijssen
|
|
MA, Vergouwe
|
|
MN, van Dijk
|
|
JG, Rees
|
|
M, Frants
|
|
RR, Brown
|
|
P. Major and minor form of hereditary hyperekplexia.
|
|
Mov Disord.
|
|
2002;17:826–30.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12210885" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12210885</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.tsai.2004.893">Tsai
|
|
CH, Chang
|
|
FC, Su
|
|
YC, Tsai
|
|
FJ, Lu
|
|
MK, Lee
|
|
CC, Kuo
|
|
CC, Yang
|
|
YW, Lu
|
|
CS. Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family.
|
|
Neurology.
|
|
2004;63:893–6.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15365143" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15365143</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.vergouwe.1997.172">Vergouwe
|
|
MN, Tijssen
|
|
MA, Shiang
|
|
R, van Dijk
|
|
JG, al Shahwan
|
|
S, Ophoff
|
|
RA, Frants
|
|
RR. Hyperekplexia-like syndromes without mutations in the GLRA1 gene.
|
|
Clin Neurol Neurosurg.
|
|
1997;99:172–8.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9350397" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9350397</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.vigevano.1989.216">Vigevano
|
|
F, Di Capua
|
|
M, Dalla Bernardina
|
|
B.
|
|
Startle disease: an avoidable cause of sudden infant death.
|
|
Lancet.
|
|
1989;1:216.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/2563117" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2563117</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.wartenberg.1941.553">Wartenberg
|
|
R.
|
|
Head retraction reflex.
|
|
Am J Med Sci.
|
|
1941;201:553–61.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="hyperek.REF.zhang.2019.e2068">Zhang
|
|
C, Wang
|
|
S-G, Wang
|
|
Y, Liu
|
|
X-L, Cao
|
|
L. Teaching Video NeuroImages: Cautious walking gait in siblings with hereditary hyperekplexia.
|
|
Neurology.
|
|
2019;92:e2068–e2069.
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/31010918" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31010918</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1260_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Bettina Balint</span>, MD<div class="affiliation small">Department of Clinical and Movement Neurosciences<br />UCL Queen Square Institute of Neurology<br />London, United Kingdom</div><div class="affiliation small">Department of Neurology<br />University Hospital Heidelberg<br />Heidelberg, Germany<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lcu@tnilab.b" class="oemail">ku.ca.lcu@tnilab.b</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Rhys Thomas</span>, PhD, FRCP<div class="affiliation small">Institute of Neuroscience<br />Newcastle University;<br />Neurosciences<br />Royal Victoria Infirmary<br />Newcastle-upon-Tyne, United Kingdom<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ku.ca.lcn@samoht.syhr" class="oemail">ku.ca.lcn@samoht.syhr</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">July 31, 2007</span>; Last Update: <span itemprop="dateModified">December 19, 2019</span>.</p><h3>Copyright</h3><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><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Balint B, Thomas R. Hereditary Hyperekplexia Overview. 2007 Jul 31 [Updated 2019 Dec 19]. 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></p></div><div class="small-screen-prev"><a href="/books/n/gene/hht/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/accpn/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobhyperekTcomplexgeneticneurodevelopme"><div id="hyperek.T.complex_genetic_neurodevelopme" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Complex Genetic Neurodevelopmental Disorders with an Excessive Startle Response</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1260/table/hyperek.T.complex_genetic_neurodevelopme/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hyperek.T.complex_genetic_neurodevelopme_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing Clinical Features</th><th id="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference <sup>1</sup></th></tr></thead><tbody><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ARHGEF9</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-infantile epileptic encephalopathy 8</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Severe ID</div></li><li class="half_rhythm"><div>Epilepsy (often intractable focal seizures or febrile seizures)</div></li><li class="half_rhythm"><div>Dysmorphic features</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/300607" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">300607</a></td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>ASNS</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Asparagine synthetase deficiency</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Profound DD & progressive encephalopathy</div></li><li class="half_rhythm"><div>Microcephaly</div></li><li class="half_rhythm"><div>Hypotonia followed by spastic quadriplegia</div></li><li class="half_rhythm"><div>Seizures</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/as-def/?report=reader">Asparagine Synthetase Deficiency</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CACNA1A</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-infantile epileptic encephalopathy 42</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Epileptic encephalopathy w/myoclonic epilepsy</div></li><li class="half_rhythm"><div>Myoclonic seizures provoked by tactile stimuli & spontaneous & reflex seizures to noise & touch</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/617106" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">617106</a></td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CLPB</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CLPB deficiency (3-methylglutaconic aciduria)</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Congenital or infantile cataracts</div></li><li class="half_rhythm"><div>Neutropenia</div></li><li class="half_rhythm"><div>Other neurologic signs: hypotonia, spasticity, ataxia, dystonia, epilepsy, or ID</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/clpb-def/?report=reader">CLPB Deficiency</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CRLF1</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Crisponi syndrome</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Dysmorphic features, camptodactyly</div></li><li class="half_rhythm"><div>Facial & bulbar weakness</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ciss/?report=reader">Cold-Induced Sweating Syndrome Including Crisponi Syndrome</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>CTNNB1</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>CTNNB1</i>-related syndrome</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hyperekplexia is rare in this entity (single case report)</div></li><li class="half_rhythm"><div>Later onset of hyperekplexia (not congenital but in childhood) & atypical pattern (no generalized stiffness induced by startle)</div></li><li class="half_rhythm"><div>No congenital stiffness</div></li><li class="half_rhythm"><div>Progressive neurologic involvement w/additional signs (ID, ataxia, spasticity)</div></li><li class="half_rhythm"><div>Microcephaly</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ctnnb1-ndd/?report=reader">CTNNB1 Neurodevelopmental Disorder</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GPHN</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Molybdenum cofactor deficiency, complementation group C</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Intractable seizures</div></li><li class="half_rhythm"><div>Severe psychomotor retardation</div></li><li class="half_rhythm"><div>Hypotonia combined w/hyperreflexia</div></li><li class="half_rhythm"><div>Usually lethal in infancy</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/mc-def/?report=reader">Molybdenum Cofactor Deficiency</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>HEXA</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Tay-Sachs disease</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>DD or regression</div></li><li class="half_rhythm"><div>Visual impairment</div></li><li class="half_rhythm"><div>Epilepsy</div></li><li class="half_rhythm"><div>Later: macrocephaly, decerebrate posturing, dysphagia, progression to unresponsive vegetative state</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/tay-sachs/?report=reader">Hexosaminidase A Deficiency</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>RPS6KA3</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Coffin-Lowry syndrome</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>ID</div></li><li class="half_rhythm"><div>Facial dysmorphism, tapering digits, & skeletal deformity</div></li><li class="half_rhythm"><div>Besides hyperekplexia, there may be other types of stimulus-induced drop attacks (e.g., cataplexy-like episodes)</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/cls/?report=reader">Coffin-Lowry Syndrome</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SCN8A</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-infantile epileptic encephalopathy 13</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Epileptic encephalopathy w/DD & ID</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/scn8a-ee/?report=reader"><i>SCN8A</i>-Related Epilepsy with Encephalopathy</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC6A9</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">GLYT1 encephalopathy</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia > hypertonicity</div></li><li class="half_rhythm"><div>Arthrogryposis</div></li><li class="half_rhythm"><div>Respiratory failure</div></li><li class="half_rhythm"><div>Dysmorphic features</div></li><li class="half_rhythm"><div>Encephalopathy</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/glyt1-dis/?report=reader">GLYT1 Encephalopathy</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SUOX</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Isolated sulfite oxidase deficiency</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Progressive epileptic encephalopathy</div></li><li class="half_rhythm"><div>Other neurologic features: opisthotonus, spastic quadriplegia, pyramidal signs</div></li><li class="half_rhythm"><div>Microcephaly, dysmorphic features</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/iso-def/?report=reader">Isolated Sulfite Oxidase Deficiency</a>
|
|
</td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TRAK1</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-infantile epileptic encephalopathy 68</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Progressive epileptic encephalopathy</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">OMIM <a href="https://omim.org/entry/618201" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618201</a></td></tr><tr><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>TSEN54</i>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pontocerebellar hypoplasia type 2</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Generalized clonus ("jitteriness")</div></li><li class="half_rhythm"><div>Delayed developmental (motor & cognitive) milestones</div></li><li class="half_rhythm"><div>Other neurologic signs: spasticity, chorea, visual impairment, epilepsy</div></li></ul>
|
|
</td><td headers="hd_h_hyperek.T.complex_genetic_neurodevelopme_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/pc-hypo-p/?report=reader"><i>TSEN54</i>-Related Pontocerebellar Hypoplasia</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hyperek.TF.1.1"><p class="no_margin">OMIM phenotype entry or citation is provided if a related <i>GeneReview</i> is not available</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobhyperekTglra1glrbandslc6a5relatedh"><div id="hyperek.T.glra1_glrb_and_slc6a5related_h" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>GLRA1</i>, <i>GLRB</i>, and <i>SLC6A5</i>-Related Hereditary Hyperekplexia: Modes of Inheritance and Methods of Variant Detection</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1260/table/hyperek.T.glra1_glrb_and_slc6a5related_h/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__hyperek.T.glra1_glrb_and_slc6a5related_h_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of HPX Attributed to Mutation of Gene</th><th id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI <sup>1</sup></th><th id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant Identified by Method <sup>2</sup></th></tr><tr><th headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4" id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></th><th headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4" id="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></th></tr></thead><tbody><tr><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GLRA1</i>
|
|
</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">61%-63%</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD & AR</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~95%</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 5.</td></tr><tr><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>GLRB</i>
|
|
</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">12%-14%</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD & AR</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">11/12</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/12 <sup>6</sup></td></tr><tr><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC6A5</i>
|
|
</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR (rarely AD <sup>7</sup>)</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">24/24</td><td headers="hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_1_4 hd_h_hyperek.T.glra1_glrb_and_slc6a5related_h_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; HPX = hereditary hyperekplexia; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="hyperek.TF.2.1"><p class="no_margin">~85% were AR and ~15% were AD [<a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al 2013</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="hyperek.TF.2.2"><p class="no_margin">Since the study of <a class="bibr" href="#hyperek.REF.thomas.2013.3085" rid="hyperek.REF.thomas.2013.3085">Thomas et al [2013]</a>, additional affected individuals have been reported, many as case studies. For additional reported variants, see <a href="http://www.hgmd.cf.ac.uk/ac/index.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Human Genome Mutation Database</a> [<a class="bibr" href="#hyperek.REF.stenson.2020.1197" rid="hyperek.REF.stenson.2020.1197">Stenson et al 2020</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="hyperek.TF.2.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="hyperek.TF.2.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="hyperek.TF.2.5"><p class="no_margin">Deletion of exons 1 through 7 is common in the Turkish population [<a class="bibr" href="#hyperek.REF.thomas.2015.341" rid="hyperek.REF.thomas.2015.341">Thomas et al 2015</a>]. Deletion of exons 1 through 6 [<a class="bibr" href="#hyperek.REF.brune.1996.989" rid="hyperek.REF.brune.1996.989">Brune et al 1996</a>] and of 4 through 7 have also been reported [<a class="bibr" href="#hyperek.REF.chung.2010.9612" rid="hyperek.REF.chung.2010.9612">Chung et al 2010</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="hyperek.TF.2.6"><p class="no_margin">
|
|
<a class="bibr" href="#hyperek.REF.chung.2013.927" rid="hyperek.REF.chung.2013.927">Chung et al [2013]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="hyperek.TF.2.7"><p class="no_margin">
|
|
<a class="bibr" href="#hyperek.REF.rees.2006.801" rid="hyperek.REF.rees.2006.801">Rees et al [2006]</a>
|
|
</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.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></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal105 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/3968615.js" snapshot="books"></script></body>
|
|
</html>
|