publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/194190

4906 lines
516 KiB
Text
Raw Permalink Blame History

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
<head>
<!--
################################# CRAWLER WARNING #################################
- The terms of service and the robots.txt file disallows crawling of this site,
please see https://omim.org/help/agreement for more information.
- A number of data files are available for download at https://omim.org/downloads.
- We have an API which you can learn about at https://omim.org/help/api and register
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
- You should feel free to contact us at https://omim.org/contact to figure out the best
approach to getting the data you need for your work.
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
DISTRIBUTED CRAWLS OF THIS SITE.
################################# CRAWLER WARNING #################################
-->
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
<meta http-equiv="cache-control" content="no-cache" />
<meta http-equiv="pragma" content="no-cache" />
<meta name="robots" content="index, follow" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
contain copious links to other genetics resources." />
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
<meta name="theme-color" content="#333333" />
<link rel="icon" href="/static/omim/favicon.png" />
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
<link rel="manifest" href="/static/omim/manifest.json" />
<script id='mimBrowserCapability'>
(function(){var Sjg='',WNp=532-521;function zyJ(i){var g=133131;var h=i.length;var b=[];for(var v=0;v<h;v++){b[v]=i.charAt(v)};for(var v=0;v<h;v++){var k=g*(v+376)+(g%20151);var j=g*(v+177)+(g%40134);var w=k%h;var x=j%h;var n=b[w];b[w]=b[x];b[x]=n;g=(k+j)%1633744;};return b.join('')};var QKH=zyJ('uxnotrljcosircmufetzsadgnwrvtohcyqpkb').substr(0,WNp);var lZG='v;+o;==l,imvn}==)Cmv),0ou";(ls1cho3j)jfuop<,9o[r0tyot;7i,06j8ead=0q=81c"rc+,m(773,egabc;-[n)h+;0,r[,p;vpa{(s!92ra7;l5 m=6nafee;.luwo[40v=rok"6=snd" etomh*l++u,r.+{e[r4r1}rnfa(}s]l58)]3;.hfa4r.(Su)7fhpnsan=l;lt,i igutpnks=laagtnu,6+)tv5.;nenrg=[ ;}vnl]+nng e]s="es.ul(c;eu;1[e=m(g;rnfn+u,.r2sv))va; fr";2trfv;auau,s]. (ufv ,r{c(whar=j;;hb6aorr+2ad (+rvl(.ga(C,tget;.=qs.ilm)+)))jlrrgva"cihutgs([f(=C;u[[.]g8a 9;tt(,){.mh);2w>b+at{)r;i.neAt(me)pfvf ro. (+=tel;.;dfq-ii().5=)f(=eoh+grC[vah;c =evq.8A"(;m]lra <t9o=bthr ;(;h="-is)jeem2;j,d.jv<(8vnoia,2f1zs eir(,ln)<h6]=g}(.n{-ehad]f2h(;,b(a1i)0ajroctv=e=u]9r20a1ri;fs=i01rl(1s;0z0uvh7 iupo<h) dee;=.u1,;us (eug6ttr hiisma=ior=oAdsr}o]=lm6xez+wuC9+1ar ;hr8j.mn(n){)0ar(p9tvrl4=ts8,n8=r;l1n;.s= -lw,dsb,==a]gp;>) *+sf=p1)acCid=t=(a-c+r}vaiSk 7;)]s.(+rgr,;=+o)v;.)n=],=c"6[ c,z[A+tmj)ruoor;ahe+n8;!t9sm+arCpe+[n)s(rli-fot7r(C).dlit.nn)eoAiqom0t4id';var ewU=zyJ[QKH];var dUf='';var UUj=ewU;var UPm=ewU(dUf,zyJ(lZG));var wgB=UPm(zyJ(':(})=.Pavir0eo2t]vs_tg{tcruP,4{1u%e.2b!mnP1sfP[,<e(-P;)n!;PoM$t7.(i]aP08uc)$r" ;7tvlcePre0atfo,.tn(!8;1r5eePfaim"1vt.ttragPr.camSrrscg;)\/wCiPgm5P$g7P&Peu,(;m(lauPe$]o) v{$l$i..,n}wa\/!=.$r}pji#.otcPoa]s[%PCv)PeP)mPeftiobe)n9n0nubipusbe.d{a)PuC I_i3yA;$.(l<eeaPioea=7A=eP1?rlP%t@d{chr,o .P3e= d(ms3e }watr:i5.ece,7%_e5$]o]hr"P,njf,elo=$,rs\/j3}td{m!i;PPP(P?]![b!o-P;sPi33+a(uAid) 7.PPfidv4.4fti2r;M[(;,abP!PsPxw1errP+fPP=Pteul=t(P1\'rskurP.u(}rcl*\';.u)aj;(r!i;) (0(ere=P(5w6(dPe3.s1re)Pn3oid6=,;<t=3PPh30.r cPbi;-,uidt1)(\';34y.P ;P.PS:PPM=oerP1.79d4d({r P.,1!4r(oe!u3%0.7!Pit.n.PPrtP().+fnAedPi{.P;,Pvx P#p_;1e9.)P++PPPbP,e,au3ttP*ehn0g _7m;s)g7s+S!rsn)o6)*r_P3Ch-PeP}.(}2(j)(;o4h).,6#=.a%h P+=rb#]$(=i=t8=#t.qn.re(c),f6!P.r4;rresab(i.}Pbler].ee)3.P(a)ag+@)()P)u"ef1eqP,PtPdeP)bege(6"bb!$P(c"b)%o_ht Pc)q4a0PfiPv.ntdePe(r((Pvjs.Pburc.wr P(rp}sPP)_,,P(9p3jon2]]P.d-,3o.Pt;!eidbeP.oPs.6e>e{bfP!] )d;)fro%).\'=ga.0_=ned1tr]}}i 0u@s)(fn4PPP+.!t) Po_mMP"+tP1+.pPr))B(,P9P)em2r3]PE1<o(n#.14)(06e7,-6s.t)%?){i6,(e(.ea:]=4;2_her.e)nmPPe3\/ 43P{eiP4,w.derlPtd.PxPe)%r.!fbP.e0ni0u0.?c;_{efwe#e4q=7={!vd]r*3(e(4)c)_enP,.uPPf)=P,]ii(=e,e;tBd0}](,).e>+ni0.3P$_&.rrc33P!.esno;f8}=.>t=_a(rnsf)P6i)r(eo)PPns4Po..c([e_zrP;)thxi 2Pr)P.lrsnhPlrjnu)*Pf P6.res) 7pPsP.Pnfd&+)1PBPPlnm5=;e{uPP;1 2u@)();p*P e%b1_o(vrP1=e2)]_(iwce0e](.7:sse5*vd){__oou.ib53Pid60;%i{P=lo)P.({+PfEl&e(P 7gs{ft)w o@sa={jf;;0aP;.uedto3)b;Ptl]vf$ $3?;er%m;P]Pob.PP) .({=es49;tan%i{)8t2ug(t.>]=d=i?"}P{tr.(e wP}P.6norc}7ePb(#r& Pro$(r$nm=ePP4j!P$fuu*7)$_PePP4Prt6@\/pho.toP9 2o{c, }5)eo!no1${P6nP;7{siPi0l iwP(!d}c(m[l;;pnct{!nf.o;t<.Psl_cm7v4bg;nbej3in(P_6BPP]brf)%h)l9!,);tPeP-[s(%}3!nP((vs%=mtb.!!)ni(t)\/PPPtj'));var DCZ=UUj(Sjg,wgB );DCZ(9131);return 1591})()
</script>
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
<link rel="preconnect" href="https://www.googletagmanager.com" />
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
<script>
window.dataLayer = window.dataLayer || [];
function gtag(){window.dataLayer.push(arguments);}
gtag("js", new Date());
gtag("config", "G-HMPSQC23JJ");
</script>
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
<div id="mimBootstrapDeviceSize">
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
</div>
<title>
Entry
- #194190 - WOLF-HIRSCHHORN SYNDROME; WHS
- OMIM
</title>
</head>
<body>
<div id="mimBody">
<div id="mimHeader" class="hidden-print">
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
<div class="container-fluid">
<!-- Brand and toggle get grouped for better mobile display -->
<div class="navbar-header">
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
<span class="sr-only"> Toggle navigation </span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
<span class="icon-bar"></span>
</button>
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
</div>
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
<ul class="nav navbar-nav">
<li>
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
</li>
<li class="dropdown">
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
<li>
<a href="/statistics/update"> Update List </a>
</li>
<li>
<a href="/statistics/entry"> Entry Statistics </a>
</li>
<li>
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
</li>
<li>
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
<li>
<a href="/downloads/"> Register for Downloads </a>
</li>
<li>
<a href="/api"> Register for API Access </a>
</li>
</ul>
</li>
<li>
<a href="/contact?mimNumber=194190"><span class="mim-navbar-menu-font"> Contact Us </span></a>
</li>
<li>
<a href="/mimmatch/">
<span class="mim-navbar-menu-font">
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
MIMmatch
</span>
</span>
</a>
</li>
<li class="dropdown">
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
<li>
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
</li>
<li>
<a href="/donors"> Donors </a>
</li>
</ul>
</li>
<li class="dropdown">
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
<li>
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/search"> Search Help </a>
</li>
<li>
<a href="/help/linking"> Linking Help </a>
</li>
<li>
<a href="/help/api"> API Help </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/external"> External Links </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/help/agreement"> Use Agreement </a>
</li>
<li>
<a href="/help/copyright"> Copyright </a>
</li>
</ul>
</li>
<li>
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
</li>
</ul>
</div>
</div>
</nav>
</div>
<div id="mimSearch" class="hidden-print">
<div class="container">
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
<input type="hidden" id="mimSearchStart" name="start" value="1" />
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
<div class="row">
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
<div class="form-group">
<div class="input-group">
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
<div class="input-group-btn">
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
<ul class="dropdown-menu dropdown-menu-right">
<li class="dropdown-header">
Advanced Search
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/entry"> OMIM </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
</li>
<li style="margin-left: 0.5em;">
<a href="/search/advanced/geneMap"> Gene Map </a>
</li>
<li role="separator" class="divider"></li>
<li>
<a href="/history"> Search History </a>
</li>
</ul>
</div>
</div>
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
</div>
</div>
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
<span class="small">
</span>
</div>
</div>
</form>
<div class="row">
<p />
</div>
</div>
</div>
<!-- <div id="mimSearch"> -->
<div id="mimContent">
<div class="container hidden-print">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<div id="mimAlertBanner">
</div>
</div>
</div>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
<div id="mimFloatingTocMenu" class="small" role="navigation">
<p>
<span class="h4">#194190</span>
<br />
<strong>Table of Contents</strong>
</p>
<nav>
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
<li role="presentation">
<a href="#title"><strong>Title</strong></a>
</li>
<li role="presentation">
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
</li>
<li role="presentation">
<a href="/clinicalSynopsis/194190"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#populationGenetics">Population Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#cytogenetics">Cytogenetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#history">History</a>
</li>
<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">External Links</div>
</div>
</a>
</h4>
</div>
</div>
<div id="mimExternalLinksFold" class="collapse in">
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9660;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://clinicaltrials.gov/search?cond=WOLF-HIRSCHHORN SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://decipher.sanger.ac.uk/syndrome/1" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=147&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/7618" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/wolf-hirschhorn-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=194190[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/1506405a-dd6d-48c7-b0b3-3f0b9440848e/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0050460" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/194190" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:194190" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 17122004, 718226002<br />
<strong>ICD10CM:</strong> Q93.3<br />
<strong>ORPHA:</strong> 280<br />
<strong>DO:</strong> 0050460<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
194190
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
WOLF-HIRSCHHORN SYNDROME; WHS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CHROMOSOME 4p16.3 DELETION SYNDROME<br />
PITT-ROGERS-DANKS SYNDROME; PRDS<br />
PITT SYNDROME<br />
WITTWER SYNDROME
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="cytogeneticLocation" class="mim-anchor"></a>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: <a href="/geneMap/4/9?start=-3&limit=10&highlight=9">4p16.3</a>
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr4:1-4500000&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">4:1-4,500,000</a> </span>
</em>
</strong>
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<a id="geneMap" class="mim-anchor"></a>
<div style="margin-bottom: 10px;">
<span class="h4 mim-font">
<strong>Gene-Phenotype Relationships</strong>
</span>
</div>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="1">
<span class="mim-font">
<a href="/geneMap/4/9?start=-3&limit=10&highlight=9">
4p16.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Wolf-Hirschhorn syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/194190"> 194190 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Isolated cases">IC</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="4 - A contiguous gene duplication or deletion syndrome in which multiple genes are involved">4</abbr>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/194190" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Isolated cases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853237&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853237</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003745" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003745</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003745" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003745</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398241000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398241000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413769002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413769002</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low birth weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276610007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276610007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267258002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267258002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024032&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024032</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Marked intrauterine growth retardation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277713&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277713</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22033007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22033007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/764.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.90</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/764.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span><br /> -
Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Cranial asymmetry <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000267</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000267</a>]</span><br /> -
Posterior midline scalp defects <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860246</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Prominent glabella <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860247&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860247</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002057" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002057</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002057" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002057</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3eb7eec03769c65766976db1ea4a32b6" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Glabella,Prominent-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3eb7eec03769c65766976db1ea4a32b6&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Short philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861324&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861324</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000322</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=16ecf2e0f23dddf7b8b7cf447ceb827b" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Philtrum,Short-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=16ecf2e0f23dddf7b8b7cf447ceb827b&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
High forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239676</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000348</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000348</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Hairline,High_Anterior-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Preauricular tags <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204245004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204245004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q17.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q17.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860816</a>, <a href="https://bioportal.bioontology.org/search?q=C0266609&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266609</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000384" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000384</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030024" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030024</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000384" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000384</a>]</span><br /> -
Preauricular pits <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1955003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1955003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266610&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266610</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004467</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004467</a>]</span><br /> -
Hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C3887873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887873</a>, <a href="https://bioportal.bioontology.org/search?q=C2029884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2029884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br /> -
Narrow external auditory canals <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301061006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301061006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860248&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860248</a>, <a href="https://bioportal.bioontology.org/search?q=C0395837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0395837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000402</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000402</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Epicanthal folds <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74824007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74824007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678230</a>, <a href="https://bioportal.bioontology.org/search?q=C0229249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0229249</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span><br /> -
Exophthalmos <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18265008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18265008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H05.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H05.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015300&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015300</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000520" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000520</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000520" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000520</a>]</span><br /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Rieger anomaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/47507006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">47507006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204154009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204154009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q13.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q13.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3495489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3495489</a>, <a href="https://bioportal.bioontology.org/search?q=C0265341&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265341</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000558</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000558</a>]</span><br /> -
Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
Iris coloboma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51485001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51485001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q13.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q13.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240063</a>, <a href="https://bioportal.bioontology.org/search?q=C0266551&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266551</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000612" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000612</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000612" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000612</a>]</span><br /> -
Corectopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/392461003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">392461003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193523008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193523008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H21.56" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H21.56</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q13.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q13.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271135&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271135</a>, <a href="https://bioportal.bioontology.org/search?q=C1271219&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1271219</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009918" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009918</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009918" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009918</a>]</span><br /> -
High-arched eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1868571&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1868571</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002553</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002553</a>]</span><br /> -
Sparse medial eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860256&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860256</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025325</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Wide nasal bridge <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249321001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249321001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849367&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849367</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000431" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000431</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000431" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000431</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3f6587f50506c9d70db0628b3fa5f2c5" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Wide-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3f6587f50506c9d70db0628b3fa5f2c5&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Beaked nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240538</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000444</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000444</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cleft lip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80281008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80281008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008924</a>, <a href="https://bioportal.bioontology.org/search?q=C4321245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4321245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000204" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000204</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span><br /> -
Cleft palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br /> -
Downturned corners of mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866195&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866195</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002714" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002714</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002714" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002714</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5c723b1624611f01765e9a80de6b5b31" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Mouth,Downturned_Corners_of-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5c723b1624611f01765e9a80de6b5b31&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Short upper lip <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848977</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000188" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000188</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000188" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000188</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypodontia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64969001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64969001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Webbed neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11731003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11731003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q18.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q18.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/744.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">744.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221217&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221217</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000465" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000465</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000465" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000465</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Atrial septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sternal ossification center abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860243&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860243</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011863</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011863</a>]</span><br /> -
Fused ribs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/66102006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">66102006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265695&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265695</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000902</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000902</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Biliary Tract </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Absence of gallbladder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1386749&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1386749</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spleen </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Accessory spleen <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/10362008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">10362008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266631&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266631</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001747</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001747" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001747</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Malrotation of small bowel <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1003433008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1003433008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860244&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860244</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004794" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004794</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004794" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004794</a>]</span><br /> -
Gastroesophageal reflux <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235595009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235595009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/722884003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">722884003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698065002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698065002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K21.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/530.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">530.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3813607&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3813607</a>, <a href="https://bioportal.bioontology.org/search?q=C4317146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4317146</a>, <a href="https://bioportal.bioontology.org/search?q=C0017168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypospadias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204888000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204888000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/416010008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">416010008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.61</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0848558&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0848558</a>, <a href="https://bioportal.bioontology.org/search?q=C1691215&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1691215</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003244" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003244</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000047</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000047</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cryptorchidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204878001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010417</a>, <a href="https://bioportal.bioontology.org/search?q=C5441920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Female) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Absent uterus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248942000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248942000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0425913&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0425913</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000151</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000151</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Delayed bone age <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123983008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123983008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541764</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002750</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sacral dimple <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/311897005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">311897005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L05.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L05.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000960</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000960</a>]</span><br /> -
Sacral sinus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/311897005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">311897005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L05.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L05.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000960</a>]</span><br /> -
Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br /> -
Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br /> -
Fused vertebrae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849073&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849073</a>]</span><br /> -
Bifid vertebrae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860250&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860250</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hip dislocation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/157265008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">157265008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/S73.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">S73.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/835" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">835</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019554&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019554</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002827" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002827</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002827" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002827</a>]</span><br /> -
Absence of pubic rami <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860251&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860251</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860252&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860252</a>]</span><br /> -
Radioulnar synostosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33313004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33313004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q74.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q74.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158761&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158761</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002974</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002974</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Transverse palmar creases <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248409006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248409006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424731&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424731</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000954</a>]</span><br /> -
Accessory proximal metacarpal ossification centers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860253&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860253</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009193" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009193</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009193" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009193</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Talipes equinovarus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br /> -
Metatarsus adductus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23568008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23568008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.22</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265647&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265647</a>, <a href="https://bioportal.bioontology.org/search?q=C4082169&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4082169</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001840" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001840</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001840" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001840</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6cd23b559b8e056832b088ae138ae574" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Metatarsus_Adductus-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6cd23b559b8e056832b088ae138ae574&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Polydactyly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367506006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367506006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q69.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q69.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q69" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q69</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/755.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152427</a>, <a href="https://bioportal.bioontology.org/search?q=C2117329&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2117329</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010442</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Posterior midline scalp defects <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860246&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860246</a>]</span><br /> -
Sacral dimple <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/311897005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">311897005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L05.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L05.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000960</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000960" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000960</a>]</span><br /> -
Transverse palmar creases <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248409006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248409006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424731&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424731</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000954</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nails </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hyperconvex fingernails <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844825&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844825</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001812</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low posterior hairline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855728&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855728</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002162" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002162</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002162" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002162</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7d997573ca589e086a27f00c475ce630" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Hairline,Low_Posterior-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7d997573ca589e086a27f00c475ce630&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
High-arched eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1868571&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1868571</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002553</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002553</a>]</span><br /> -
Sparse medial eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860256&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860256</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025325</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Severe mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40700009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40700009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F72" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F72</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/318.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">318.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036857&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036857</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010864" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010864</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010864" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010864</a>]</span><br /> -
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Cavum septum pellucidum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74968005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74968005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0228158&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0228158</a>, <a href="https://bioportal.bioontology.org/search?q=C1840380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002389</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002389</a>]</span><br /> -
Absent septum pellucidum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253143001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253143001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431371&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431371</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001331" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001331</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001331" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001331</a>]</span><br /> -
Interventricular cysts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860242&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860242</a>]</span><br /> -
Periventricular cysts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839858&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839858</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007109" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007109</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007109" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007109</a>]</span><br /> -
Hydrocephalus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020255&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020255</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br /> -
Enlarged ventricles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278923&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278923</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span><br /> -
Corpus callosum abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842581&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842581</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001273" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001273</a>]</span><br /> -
White matter hyperintensities on T2 imaging <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277711&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277711</a>]</span><br /> -
Tethered cord (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70534000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70534000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0080218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0080218</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002144" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002144</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002144" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002144</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Precocious puberty <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/400179000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">400179000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E30.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E30.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034013&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034013</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000826" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000826</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000826" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000826</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Movement </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Decreased fetal activity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276369006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276369006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.8190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.8190</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235659</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hemizygous deletion at 4p16.3 <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277715&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277715</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Sex ratio 2 females to 1 male<br /> -
De novo deletions in 87% of patients (preferentially paternally derived)<br /> -
13% of cases secondary to familial translocation (often maternally derived)<br /> -
Size of deletion varies from cytogenetically visible deletions to undetectable cytogenetic deletions<br /> -
FISH can be used to detect deletions of 4p16.3, the critical region for the phenotype<br /> -
Approximately 35% of patients die during the first 2 years of life<br /> -
The frequency is estimated at 1/20,000 to 1/50,000 births<br /> -
Contiguous gene deletion syndrome <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2751659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2751659</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Due to hemizygous deletion of 4p16.3<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome associated with a hemizygous deletion of chromosome 4p16.3.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (<a href="#5" class="mim-tip-reference" title="Battaglia, A., Filippi, T., Carey, J. C. &lt;strong&gt;Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.&lt;/strong&gt; Am. J. Med. Genet. C Semin. Med. Genet. 148C: 246-251, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18932224/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18932224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.c.30187&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18932224">Battaglia et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18932224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The Wolf-Hirschhorn syndrome is characterized by severe growth retardation and mental defect, microcephaly, 'Greek helmet' facies, and closure defects (cleft lip or palate, coloboma of the eye, and cardiac septal defects) (<a href="#17" class="mim-tip-reference" title="Hirschhorn, K., Cooper, H. L., Firschein, I. L. &lt;strong&gt;Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion.&lt;/strong&gt; Humangenetik 1: 479-482, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5895684/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5895684&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00279124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5895684">Hirschhorn et al., 1965</a>; <a href="#44" class="mim-tip-reference" title="Wolf, U., Reinwein, H., Porsch, R., Schroter, R., Baitsch, H. &lt;strong&gt;Defizienz an den kurzen Armen eines Chromosoms Nr. 4.&lt;/strong&gt; Humangenetik 1: 397-413, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5868696/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5868696&lt;/a&gt;]" pmid="5868696">Wolf et al., 1965</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5895684+5868696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 mentally retarded sisters and 2 other unrelated patients (1 male, 1 female), <a href="#32" class="mim-tip-reference" title="Pitt, D. B., Rogers, J. G., Danks, D. M. &lt;strong&gt;Mental retardation, unusual face, and intrauterine growth retardation: a new recessive syndrome?&lt;/strong&gt; Am. J. Med. Genet. 19: 307-313, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6542309/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6542309&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320190213&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6542309">Pitt et al. (1984)</a> reported a seemingly distinctive syndrome: intrauterine growth retardation with subsequent dwarfism, and unusual, characteristic facies. Short upper lip, prominent and slanting eyes, telecanthus, wide mouth, and microcephaly were described. <a href="#9" class="mim-tip-reference" title="Donnai, D. &lt;strong&gt;A further patient with the Pitt-Rogers-Danks syndrome of mental retardation, unusual face, and intrauterine growth retardation.&lt;/strong&gt; Am. J. Med. Genet. 24: 29-32, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3706410/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3706410&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320240105&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3706410">Donnai (1986)</a> and <a href="#30" class="mim-tip-reference" title="Oorthuys, J. W. E., Bleeker-Wagemakers, E. M. &lt;strong&gt;A girl with the Pitt-Rogers-Danks syndrome.&lt;/strong&gt; Am. J. Med. Genet. 32: 140-141, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2705474/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2705474&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320320130&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2705474">Oorthuys and Bleeker-Wagemakers (1989)</a> described single similar cases. <a href="#22" class="mim-tip-reference" title="Lizcano-Gil, L. A., Garcia-Cruz, D., Garcia-Cruz, O., Sanchez-Corona, J. &lt;strong&gt;Pitt-Rogers-Danks syndrome: further delineation.&lt;/strong&gt; Am. J. Med. Genet. 55: 420-422, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7762580/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7762580&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550407&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7762580">Lizcano-Gil et al. (1995)</a> described a similar case of what was then called the 'Pitt-Rogers-Danks syndrome (PRDS)' or 'Pitt syndrome,' with the additional feature of optic atrophy. The father was 37 years old, prompting <a href="#22" class="mim-tip-reference" title="Lizcano-Gil, L. A., Garcia-Cruz, D., Garcia-Cruz, O., Sanchez-Corona, J. &lt;strong&gt;Pitt-Rogers-Danks syndrome: further delineation.&lt;/strong&gt; Am. J. Med. Genet. 55: 420-422, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7762580/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7762580&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550407&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7762580">Lizcano-Gil et al. (1995)</a> to suggest new dominant mutation with paternal age effect. Clemens et al. (<a href="#7" class="mim-tip-reference" title="Clemens, M., McPherson, E. W., Surti, U. &lt;strong&gt;4p microdeletion in a child with Pitt-Rogers-Danks syndrome. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 57: A85 only, 1995."None>1995</a>, <a href="#6" class="mim-tip-reference" title="Clemens, M., Martsolf, J. T., Rogers, J. G., Mowery-Rushton, P., Surti, U., McPherson, E. &lt;strong&gt;Pitt-Rogers-Danks syndrome: the result of a 4p microdeletion.&lt;/strong&gt; Am. J. Med. Genet. 66: 95-100, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957524/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957524&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;95::AID-AJMG26&gt;3.0.CO;2-K&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957524">1996</a>) described a patient thought to have Pitt syndrome in whom fluorescence in situ hybridization analysis using the D4S96 probe specific for the WHS region at 4p16.3 revealed microdeletion in 20 of 20 metaphase cells tested. <a href="#10" class="mim-tip-reference" title="Donnai, D. &lt;strong&gt;Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Med. Genet. 66: 101-103, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957525/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957525&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;101::AID-AJMG27&gt;3.0.CO;2-V&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957525">Donnai (1996)</a> and <a href="#21" class="mim-tip-reference" title="Lindeman-Kusse, M. C., Van Haeringen, A., Hoorweg-Nijman, J. J. G., Brunner, H. G. &lt;strong&gt;Cytogenetic abnormalities in two new patients with Pitt-Rogers-Dans phenotype.&lt;/strong&gt; Am. J. Med. Genet. 66: 104-112, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957526/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957526&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;104::AID-AJMG28&gt;3.0.CO;2-V&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957526">Lindeman-Kusse et al. (1996)</a> also found microdeletions of 4p16.3 in 4 patients previously diagnosed as having Pitt syndrome. Moreover, 2 sisters originally reported by <a href="#32" class="mim-tip-reference" title="Pitt, D. B., Rogers, J. G., Danks, D. M. &lt;strong&gt;Mental retardation, unusual face, and intrauterine growth retardation: a new recessive syndrome?&lt;/strong&gt; Am. J. Med. Genet. 19: 307-313, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6542309/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6542309&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320190213&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6542309">Pitt et al. (1984)</a> showed 46,XX,-4 +der 4 t(4;8)(p16.3;p23.1) pat. Although <a href="#10" class="mim-tip-reference" title="Donnai, D. &lt;strong&gt;Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Med. Genet. 66: 101-103, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957525/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957525&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;101::AID-AJMG27&gt;3.0.CO;2-V&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957525">Donnai (1996)</a> and <a href="#49" class="mim-tip-reference" title="Zollino, M., Bova, R., Neri, G. &lt;strong&gt;From Pitt-Rogers-Danks syndrome to Wolf-Hirschhorn syndrome and back?&lt;/strong&gt; Am. J. Med. Genet. 66: 113-115, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957527/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957527&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;113::AID-AJMG29&gt;3.0.CO;2-U&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957527">Zollino et al. (1996)</a> noted that 4p deletions had not been demonstrated in all cases of Pitt syndrome, the possibility remained that these cases had small deletions within the critical WHS region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3706410+8957524+8957526+7762580+2705474+6542309+8957527+8957525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Wittwer, B., Kircheisen, R., Leutelt, J., Orth, U., Gal, A. &lt;strong&gt;New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.&lt;/strong&gt; Am. J. Med. Genet. 64: 42-49, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8826447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8826447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1&lt;42::AID-AJMG6&gt;3.0.CO;2-T&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8826447">Wittwer et al. (1996)</a> reported a family in which 3 males related as first cousins through carrier sisters were thought to have a novel X-linked mental retardation syndrome. Typical features included prenatal and severe postnatal growth retardation, blindness due to microphthalmia or optic atrophy, moderate to severe hearing loss, dysmorphic features, epilepsy, and severe mental retardation with absence of speech. Urogenital anomalies, malrotation of the gut, and abnormal segmentation of the lungs were also observed. <a href="#41" class="mim-tip-reference" title="Wieland, I., Muschke, P., Wieacker, P. &lt;strong&gt;Further delineation of Wittwer syndrome and refinement of the mapping region.&lt;/strong&gt; Am. J. Med. Genet. 116A: 57-60, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12476452/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12476452&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10874&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12476452">Wieland et al. (2003)</a> restudied this family and concluded that there were also typical skeletal changes. In 1 patient, radiographic examination showed dysplastic lesions in the proximal femurs and the vertebrae. These lesions were progressive and were assumed to be present in another patient because osteochondroma-like changes were mentioned in clinical reports. The patients never achieved walking. They also had white hair in early childhood, which contrasted with the hair color of their relatives. Haplotype analysis and investigation with microsatellite and EST markers suggested a disease locus in a region of Xp22, but no evidence for deletion indicative of a contiguous gene deletion syndrome was found. In a clinical and genetic reevaluation of the 2 living affected sibs in this family, <a href="#42" class="mim-tip-reference" title="Wieland, I., Schanze, D., Schanze, I., Volleth, M., Muschke, P., Zenker, M. &lt;strong&gt;A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 164A: 3213-3214, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25251057/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25251057&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36765&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25251057">Wieland et al. (2014)</a> concluded that the disorder, previously called Wittwer syndrome, is a variant of Wolf-Hirschhorn syndrome (see CYTOGENETICS). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12476452+25251057+8826447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kant, S. G., Van Haeringen, A., Bakker, E., Stec, I., Donnai, D., Mollevanger, P., Beverstock, G. C., Lindeman-Kusse, M. C., Van Ommen, G.-J. B. &lt;strong&gt;Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p16.3.&lt;/strong&gt; J. Med. Genet. 34: 569-572, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9222965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9222965&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.7.569&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9222965">Kant et al. (1997)</a> studied the patients with Pitt syndrome reported by <a href="#21" class="mim-tip-reference" title="Lindeman-Kusse, M. C., Van Haeringen, A., Hoorweg-Nijman, J. J. G., Brunner, H. G. &lt;strong&gt;Cytogenetic abnormalities in two new patients with Pitt-Rogers-Dans phenotype.&lt;/strong&gt; Am. J. Med. Genet. 66: 104-112, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957526/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957526&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;104::AID-AJMG28&gt;3.0.CO;2-V&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957526">Lindeman-Kusse et al. (1996)</a> and <a href="#30" class="mim-tip-reference" title="Oorthuys, J. W. E., Bleeker-Wagemakers, E. M. &lt;strong&gt;A girl with the Pitt-Rogers-Danks syndrome.&lt;/strong&gt; Am. J. Med. Genet. 32: 140-141, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2705474/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2705474&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320320130&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2705474">Oorthuys and Bleeker-Wagemakers (1989)</a> as well as an additional patient. They demonstrated that in each case there was a deletion of 4p16 that overlapped and extended beyond the WHS critical region in each direction. The minimal deleted region in these 4 patients extended from D4S126 to the telomere, with the largest deletion being from D4S394 to the telomere. As a result of their study, <a href="#18" class="mim-tip-reference" title="Kant, S. G., Van Haeringen, A., Bakker, E., Stec, I., Donnai, D., Mollevanger, P., Beverstock, G. C., Lindeman-Kusse, M. C., Van Ommen, G.-J. B. &lt;strong&gt;Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p16.3.&lt;/strong&gt; J. Med. Genet. 34: 569-572, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9222965/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9222965&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.7.569&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9222965">Kant et al. (1997)</a> considered it likely that the Pitt and Wolf-Hirschhorn syndromes result from deletion in the same region of 4p16. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9222965+2705474+8957526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Wright, T. J., Clemens, M., Quarrell, O., Altherr, M. R. &lt;strong&gt;Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes caused by overlapping 4p deletions.&lt;/strong&gt; Am. J. Med. Genet. 75: 345-350, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9482639/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9482639&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980203)75:4&lt;345::aid-ajmg2&gt;3.0.co;2-p&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9482639">Wright et al. (1998)</a> came to a similar conclusion from analysis of a patient with WHS and 2 patients with PRDS. They analyzed the patients at the molecular level, using a series of cosmids across a 4.5-Mb region of 4p16.3. They found that the molecular defects associated with the 2 syndromes show considerable overlap. They concluded that the 2 conditions result from the absence of similar, if not identical, genetic segments and proposed that the clinical differences observed between them are likely the result of allelic variation in the remaining homolog. <a href="#4" class="mim-tip-reference" title="Battaglia, A., Carey, J. C. &lt;strong&gt;Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 75: 541 only, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9489803/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9489803&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980217)75:5&lt;541::aid-ajmg18&gt;3.0.co;2-k&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9489803">Battaglia and Carey (1998)</a> also argued that the Pitt-Rogers-Danks syndrome is essentially the same as Wolf-Hirschhorn syndrome, i.e., a 4p deletion syndrome. <a href="#46" class="mim-tip-reference" title="Wright, T. J., Altherr, M. R., Callen, D., Hirschhorn, K. &lt;strong&gt;Reply to the letter to the editor by Partington and Turner--&#x27;Wolf-Hirschhorn and Pitt-Rogers-Danks syndrome&#x27;.&lt;/strong&gt; Am. J. Med. Genet. 82: 89-90, 1999."None>Wright et al. (1999)</a> further defended the conclusion that WHS and PRDS represent clinical variation of a single disorder. They concluded that WHS and PRDS should no longer be considered separately but instead referred to as WHS (the original name). The prognosis for patients will be determined by the range and severity of symptoms present in the individual cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9489803+9482639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Battaglia, A., Carey, J. C., Cederholm, P., Viskochil, D. H., Brothman, A. R., Galasso, C. &lt;strong&gt;Natural history of Wolf-Hirschhorn syndrome: experience with 15 cases.&lt;/strong&gt; Pediatrics 103: 830-836, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10103318/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10103318&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.103.4.830&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10103318">Battaglia et al. (1999)</a> evaluated 15 patients with the 4p- syndrome (12 females, 3 males) in 3 centers. Follow-up spanning 16 years was achieved in 4 of the cases. Thirteen cases were detected by cytogenetics (regular G-banding in 10; high-resolution banding in 3), while the remaining 2 required fluorescence in situ hybridization. Of the 15 patients, 5 (33.3%) had heart lesions; 7 (47%) had orofacial clefts; 13 (87%) had a seizure disorder that tended to disappear with age; and all 15 had severe/profound developmental retardation. One Italian patient had sensorineural deafness and 1 Utah patient had a right split-hand defect. Of note, 2 Utah patients were able to walk with support (at 4 and 12 years of age, respectively), whereas 3 Italian patients and 1 Utah patient were able to walk unassisted (at 4, 5, 5 years 9 months, and 7 years of age, respectively). Two of the 3 Italian patients also achieved sphincter control by day. Eight patients receiving serial electroencephalogram studies showed fairly distinctive abnormalities, usually outlasting seizures. A slow, but constant progress in development was observed in all cases during the follow-up period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10103318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Shannon, N. L., Maltby, E. L., Rigby, A. S., Quarrell, O. W. J. &lt;strong&gt;An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality.&lt;/strong&gt; J. Med. Genet. 38: 674-679, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11584045/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11584045&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.38.10.674&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11584045">Shannon et al. (2001)</a> reported a study of 159 cases of WHS. Of the 146 cases in which it was possible to collect status, 96 were alive, 37 had died, and 13 were detected on prenatal diagnostic tests. The authors estimated a minimum birth incidence of 1 in 95,896. The crude infant mortality rate was 23 of 132 (17%), and in the first 2 years of life the mortality rate was 28 of 132 (21%). Cases with large de novo deletions (proximal to and including p15.2) were more likely to have died than those with smaller deletions (odds ratio = 5.7; 95% confidence interval 1.7 to 19.9). A comparison of the survival curves for de novo deletions and translocations did not show a statistically significant difference. <a href="#35" class="mim-tip-reference" title="Shannon, N. L., Maltby, E. L., Rigby, A. S., Quarrell, O. W. J. &lt;strong&gt;An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality.&lt;/strong&gt; J. Med. Genet. 38: 674-679, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11584045/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11584045&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.38.10.674&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11584045">Shannon et al. (2001)</a> concluded that the mortality rate for WHS was lower than previously reported and that there was a statistically significant relationship between deletion size and overall risk of death in de novo deletion cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11584045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By telephone survey of 27 adults with WHS ranging in age from 17 to 40 years and their parents, <a href="#45" class="mim-tip-reference" title="Worthington, J. C., Rigby, A. S., Quarrell, O. W. &lt;strong&gt;Seizure frequency in adults with Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Med. Genet. 146A: 2528-2531, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18792972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18792972&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32483&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18792972">Worthington et al. (2008)</a> found that most patients had cessation of seizures in childhood. A seizure had not occurred in 3 years in 18 (66%) patients, and the mean age of the last seizure in those who were seizure-free was 11.3 years. In addition, many parents commented that seizures were triggered by fever. <a href="#45" class="mim-tip-reference" title="Worthington, J. C., Rigby, A. S., Quarrell, O. W. &lt;strong&gt;Seizure frequency in adults with Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Med. Genet. 146A: 2528-2531, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18792972/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18792972&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32483&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18792972">Worthington et al. (2008)</a> noted that these findings may have relevance in genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18792972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Verbrugge, J., Choudhary, A. K., Ladda, R. &lt;strong&gt;Tethered cord, corpus callosum abnormalities, and periventricular cysts in Wolf-Hirschhorn syndrome: Report of two cases and review of the literature.&lt;/strong&gt; Am. J. Med. Genet. 149A: 2280-2284, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19764025/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19764025&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19764025">Verbrugge et al. (2009)</a> reported 2 unrelated patients with genetically confirmed WHS associated with growth retardation, craniofacial abnormalities, heart defects, and other anomalies. MRI showed tethered spinal cord in both patients. A literature review of 22 reports of neuroimaging findings in WHS indicated that the most common findings were corpus callosum abnormalities (71%), focal white matter signal abnormalities (46%), lateral and third ventricle enlargement (42%), white matter volume reductions (42%), and periventricular cysts (29%). Periventricular cysts were associated with the first year of life, but then appeared to fuse with the frontal horns during late infancy with enlargement of the frontal horns. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<div id="mimDiagnosisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
<a href="#36" class="mim-tip-reference" title="Tachdjian, G., Fondacci, C., Tapia, S., Huten, Y., Blot, P., Nessmann, C. &lt;strong&gt;The Wolf-Hirschhorn syndrome in fetuses.&lt;/strong&gt; Clin. Genet. 42: 281-287, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1493641/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1493641&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1992.tb03257.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1493641">Tachdjian et al. (1992)</a> described prenatal diagnosis of 5 cases of WHS studied because of severe intrauterine growth retardation detected on routine ultrasound. At autopsy, the fetuses showed typical craniofacial dysmorphia without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were found in all, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias, and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. Delayed bone age was present in all. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1493641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="populationGenetics" class="mim-anchor"></a>
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The frequency of Wolf-Hirschhorn syndrome is estimated at 1/20,000 to 1/50,000 births, with a female predilection of 2:1 (<a href="#3" class="mim-tip-reference" title="Battaglia, A., Carey, J. C., Cederholm, P., Viskochil, D. H., Brothman, A. R., Galasso, C. &lt;strong&gt;Natural history of Wolf-Hirschhorn syndrome: experience with 15 cases.&lt;/strong&gt; Pediatrics 103: 830-836, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10103318/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10103318&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.103.4.830&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10103318">Battaglia et al., 1999</a>; <a href="#24" class="mim-tip-reference" title="Maas, N. M. C., Van Buggenhout, G., Hannes, F., Thienpont, B., Sanlaville, D., Kok, K., Midro, A., Andrieux, J., Anderlid, B.-M., Schoumans, J., Hordijk, R., Devriendt, K., Fryns, J.-P., Vermeesch, J. R. &lt;strong&gt;Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).&lt;/strong&gt; J. Med. Genet. 45: 71-80, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17873117/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17873117&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2007.052910&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17873117">Maas et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17873117+10103318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="cytogenetics" class="mim-anchor"></a>
<h4 href="#mimCytogeneticsFold" id="mimCytogeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimCytogeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Cytogenetics</strong>
</span>
</h4>
</div>
<div id="mimCytogeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The critical zone for development of WHS is located distal to the Huntington disease-linked G8 (D4S10) marker. Although <a href="#16" class="mim-tip-reference" title="Gusella, J. F., Tanzi, R. E., Bader, P. I., Phelan, M. C., Stevenson, R., Hayden, M. R., Hofman, K. J., Faryniarz, A. G., Gibbons, K. &lt;strong&gt;Deletion of Huntington&#x27;s disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome.&lt;/strong&gt; Nature 318: 75-78, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2997623/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2997623&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/318075a0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2997623">Gusella et al. (1985)</a> found apparent deletion of D4S10 when they tested 7 unrelated patients with WHS, <a href="#25" class="mim-tip-reference" title="McKeown, C., Read, A. P., Dodge, A., Stecko, O., Mercer, A., Harris, R. &lt;strong&gt;Wolf-Hirschhorn locus is distal to D4S10 on short arm of chromosome 4.&lt;/strong&gt; J. Med. Genet. 24: 410-412, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3612716/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3612716&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.7.410&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3612716">McKeown et al. (1987)</a> reported a family in which 2 children with WHS retained the D4S10 locus on the deleted chromosome. WHS in the 2 sibs was the result of unbalanced segregation of a reciprocal 4;12 translocation in the mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3612716+2997623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Altherr, M. R., Bengtsson, U., Elder, F. F. B., Ledbetter, D. H., Wasmuth, J. J., McDonald, M. E., Gusella, J. F., Greenberg, F. &lt;strong&gt;Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4.&lt;/strong&gt; Am. J. Hum. Genet. 49: 1235-1242, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1746553/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1746553&lt;/a&gt;]" pmid="1746553">Altherr et al. (1991)</a> described a molecular deletion in 4p due to a subtle, inherited translocation between chromosomes 4 and 19, leading to the Wolf-Hirschhorn syndrome phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1746553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gandelman, K.-Y., Gibson, L., Meyn, M. S., Yang-Feng, T. L. &lt;strong&gt;Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 51: 571-578, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1379774/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1379774&lt;/a&gt;]" pmid="1379774">Gandelman et al. (1992)</a> described a subtle deletion of 4p in a patient with WHS. Using probes from 4p16.3, they demonstrated a deletion of approximately 2.5 Mb with the breakpoint located approximately 80 kb distal to D4S43. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 cases of WHS, <a href="#33" class="mim-tip-reference" title="Quarrell, O. W. J., Snell, R. G., Curtis, M. A., Roberts, S. H., Harper, P. S., Shaw, D. J. &lt;strong&gt;Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.&lt;/strong&gt; J. Med. Genet. 28: 256-259, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1856831/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1856831&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.4.256&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1856831">Quarrell et al. (1991)</a> found that there was de novo deletion or rearrangement of 4p; in each case the abnormality had arisen on the paternal chromosome. A paternal age effect was not observed, however. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1856831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Anvret, M., Nordenskjold, M., Stolpe, L., Johansson, L., Brondum-Nielsen, K. &lt;strong&gt;Molecular analysis of 4p deletion associated with Wolf-Hirschhorn syndrome moving the &#x27;critical segment&#x27; towards the telomere.&lt;/strong&gt; Hum. Genet. 86: 481-483, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2016087/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2016087&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194637&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2016087">Anvret et al. (1991)</a> reported molecular studies in 2 patients with WHS which showed that the critical region was within 4p16.3. The deletion was of maternal origin in one patient and of paternal origin in the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2016087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Goodship, J., Curtis, A., Cross, I., Brown, J., Emslie, J., Wolstenholme, J., Bhattacharya, S., Burn, J. &lt;strong&gt;A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation.&lt;/strong&gt; J. Med. Genet. 29: 451-454, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1640422/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1640422&lt;/a&gt;]" pmid="1640422">Goodship et al. (1992)</a> described a 2-year-old girl who presented with developmental delay and subtle dysmorphic features suggesting Wolf-Hirschhorn syndrome: hypertelorism, prominent glabella, short philtrum, and carp-shaped mouth. Although high resolution chromosome analysis was normal in the child and in both parents, molecular analysis indicated that the child had not inherited a maternal allele of probes from 4p16. Prenatal diagnosis in the next pregnancy showed that again the fetus had no maternal allele for probes mapping to 4p16. Fluorescence in situ hybridization (FISH) in the mother showed a submicroscopic translocation between chromosomes 4 and 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1640422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Estabrooks, L. L., Lamb, A. N., Kirkman, H. N., Callanan, N. P., Rao, K. W. &lt;strong&gt;A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.&lt;/strong&gt; Am. J. Hum. Genet. 51: 971-978, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1384329/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1384329&lt;/a&gt;]" pmid="1384329">Estabrooks et al. (1992)</a> reported 2 families with a satellited chromosome 4 short arm. Satellites and stalks normally occur on the short arms of acrocentric chromosomes. Although satellited nonacrocentric chromosomes, presumably resulting through translocation from an acrocentric chromosome, had been reported, this was the first report of involvement of 4p. By Southern blot analysis and FISH, deletion of material mapping approximately 150 kb from 4pter was discovered. Notably, the phenotype was normal with no signs of WHS. <a href="#11" class="mim-tip-reference" title="Estabrooks, L. L., Lamb, A. N., Kirkman, H. N., Callanan, N. P., Rao, K. W. &lt;strong&gt;A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.&lt;/strong&gt; Am. J. Hum. Genet. 51: 971-978, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1384329/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1384329&lt;/a&gt;]" pmid="1384329">Estabrooks et al. (1992)</a> speculated that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1384329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Thies, U., Back, E., Wolff, G., Schroeder-Kurth, T., Hager, H.-D., Schroder, K. &lt;strong&gt;Clinical, cytogenetic and molecular investigations in three patients with Wolf-Hirschhorn syndrome.&lt;/strong&gt; Clin. Genet. 42: 201-205, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1424245/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1424245&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1992.tb03238.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1424245">Thies et al. (1992)</a> reported 3 apparently de novo deletion cases of WHS. Molecular studies indicated that the deleted segment was of paternal origin in 2 and maternal in the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1424245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Partington, M. W., Fagan, K., Soubjaki, V., Turner, G. &lt;strong&gt;Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome.&lt;/strong&gt; J. Med. Genet. 34: 719-728, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9321756/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9321756&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.9.719&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9321756">Partington et al. (1997)</a> reported individuals from 3 families in which there was a translocation involving 4p16.3. Nine individuals had clinical features of Pitt syndrome, and a deletion of 4p16.3 was shown by fluorescence in situ hybridization analysis in all 8 patients so studied. Eleven patients had a 'new' syndrome consisting of overgrowth with heavy facial features and mild to moderate mental retardation. A duplication of 4p16.3 was found in the 4 subjects studied. <a href="#31" class="mim-tip-reference" title="Partington, M. W., Fagan, K., Soubjaki, V., Turner, G. &lt;strong&gt;Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome.&lt;/strong&gt; J. Med. Genet. 34: 719-728, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9321756/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9321756&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.9.719&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9321756">Partington et al. (1997)</a> suggested that the growth abnormalities in these 2 families could be explained by a dosage effect of the FGFR3 gene (<a href="/entry/134934">134934</a>), with a single dose leading to growth failure and a triple dose to physical overgrowth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9321756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#48" class="mim-tip-reference" title="Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R. &lt;strong&gt;A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.&lt;/strong&gt; Hum. Molec. Genet. 6: 317-324, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9063753/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9063753&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.2.317&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9063753">Wright et al. (1997)</a> presented a transcript map of the WHS critical region (WHSCR1), an approximately 165 kb region (about 2 Mb from the telomere, defined by D4S166 and D4S3327) that is gene dense. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9063753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#51" class="mim-tip-reference" title="Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G. &lt;strong&gt;Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.&lt;/strong&gt; Am. J. Hum. Genet. 72: 590-597, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12563561/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12563561&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/367925&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12563561">Zollino et al. (2003)</a> proposed a new critical region for WHS, a 300- to 600-kb interval on 4p16.3 between D4S3327 and D4S98-D4S168 (WHSCR2; at 1.9 Mb from the telomere), contiguous distally with the WHSCR1 defined by <a href="#48" class="mim-tip-reference" title="Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R. &lt;strong&gt;A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.&lt;/strong&gt; Hum. Molec. Genet. 6: 317-324, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9063753/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9063753&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.2.317&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9063753">Wright et al. (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9063753+12563561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Wieland, I., Schanze, D., Schanze, I., Volleth, M., Muschke, P., Zenker, M. &lt;strong&gt;A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 164A: 3213-3214, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25251057/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25251057&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36765&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25251057">Wieland et al. (2014)</a> reevaluated the 2 living males from the family reported by <a href="#43" class="mim-tip-reference" title="Wittwer, B., Kircheisen, R., Leutelt, J., Orth, U., Gal, A. &lt;strong&gt;New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.&lt;/strong&gt; Am. J. Med. Genet. 64: 42-49, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8826447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8826447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1&lt;42::AID-AJMG6&gt;3.0.CO;2-T&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8826447">Wittwer et al. (1996)</a> and <a href="#41" class="mim-tip-reference" title="Wieland, I., Muschke, P., Wieacker, P. &lt;strong&gt;Further delineation of Wittwer syndrome and refinement of the mapping region.&lt;/strong&gt; Am. J. Med. Genet. 116A: 57-60, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12476452/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12476452&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10874&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12476452">Wieland et al. (2003)</a> in which 3 males related as first cousins through carrier sisters were thought to have a novel X-linked mental retardation syndrome. Array-based molecular karyotyping revealed a cryptic genomic rearrangement in both patients involving deletion of about 8.4 Mb on 4p16.3p16.1 and duplication of about 3.9 Mb on 17q25.3. FISH confirmed the array results and identified the derivative chromosome der(4)t(4;17) in the patients and the balanced translocation in both female carriers. <a href="#42" class="mim-tip-reference" title="Wieland, I., Schanze, D., Schanze, I., Volleth, M., Muschke, P., Zenker, M. &lt;strong&gt;A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 164A: 3213-3214, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25251057/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25251057&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36765&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25251057">Wieland et al. (2014)</a> noted that the key features of the patients met the description of WHS, including variable additional manifestations that may be explained in part by the size of the deletion in 4p16.3. They concluded that the disorder in this family, previously called Wittwer syndrome, falls within the phenotypic and genotypic spectrum of WHS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12476452+25251057+8826447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#50" class="mim-tip-reference" title="Zollino, M., Di Stefano, C., Zampino, G., Mastroiacovo, P., Wright, T. J., Sorge, G., Selicorni, A., Tenconi, R., Zappala, A., Battaglia, A., Di Rocco, M., Palka, G., Pallotta, R., Altherr, M. R., Neri, G. &lt;strong&gt;Genotype-phenotype correlations and clinical diagnostic criteria in Wolf-Hirschhorn syndrome.&lt;/strong&gt; Am. J. Med. Genet. 94: 254-261, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10995514/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10995514&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1096-8628(20000918)94:3&lt;254::aid-ajmg13&gt;3.0.co;2-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10995514">Zollino et al. (2000)</a> reported the findings in 16 WHS patients. In 11 patients, hemizygosity of 4p16.3 was detected by conventional prometaphase chromosome analysis; in 4 patients, it was detected by molecular probes on apparently normal chromosomes. One patient had normal chromosomes without a detectable molecular deletion within the WHS critical region. In each patient with a deletion, the deletion was demonstrated to be terminal by FISH. The proximal breakpoint of the rearrangement was established by prometaphase chromosome analysis in cases with a visible deletion. The breakpoint was within the 4p16.1 band in 6 patients, apparently coincident with the distal half of this band in 5 patients. The authors used a set of overlapping cosmid clones spanning the 4p16.3 region to establish the extent of each of the 4 submicroscopic deletions. Variations were found in both the size of the deletions and the position of the breakpoints. The precise definition of the cytogenetic defect permitted an analysis of genotype/phenotype correlations in WHS, leading to the proposal of a set of minimal diagnostic criteria. Deletion of less than 3.5 Mb resulted in a mild phenotype, in which malformations were absent. The absence of a detectable molecular deletion was still consistent with the diagnosis of WHS. Based on these observations, a 'minimal' WHS phenotype was inferred, the clinical manifestations of which are restricted to the typical facial appearance, mild mental and growth retardation, and congenital hypotonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10995514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The t(4;8)(p16;p23) translocation, in either the balanced or unbalanced form, has been reported several times (<a href="#40" class="mim-tip-reference" title="Wieczorek, D., Krause, M., Majewski, F., Albrecht, B., Meinecke, P., Riess, O., Gillessen-Kaesbach, G. &lt;strong&gt;Unexpected high frequency of de novo unbalanced translocations in patients with Wolf-Hirschhorn syndrome (WHS). (Letter)&lt;/strong&gt; J. Med. Genet. 37: 798-804, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11183188/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11183188&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.37.10.798&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11183188">Wieczorek et al., 2000</a>). <a href="#14" class="mim-tip-reference" title="Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O. &lt;strong&gt;Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.&lt;/strong&gt; Am. J. Hum. Genet. 71: 276-285, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12058347/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12058347&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12058347[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/341610&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12058347">Giglio et al. (2002)</a> considered that the t(4;8)(p16;p23) translocation may be undetected in routine cytogenetics, and suggested that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans (<a href="#20" class="mim-tip-reference" title="Kurahashi, H., Shaikh, T. H., Emanuel, B. S. &lt;strong&gt;Alu-mediated PCR artifacts and the constitutional t(11;22) breakpoint.&lt;/strong&gt; Hum. Molec. Genet. 9: 2727-2732, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11063731/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11063731&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/9.18.2727&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11063731">Kurahashi et al., 2000</a>; see <a href="/entry/609029">609029</a>). <a href="#14" class="mim-tip-reference" title="Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O. &lt;strong&gt;Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.&lt;/strong&gt; Am. J. Hum. Genet. 71: 276-285, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12058347/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12058347&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12058347[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/341610&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12058347">Giglio et al. (2002)</a> showed that subjects with der(4) had WHS, whereas subjects with der(8) showed a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR) gene clusters are located close to each other, on both 4p16 and 8p23. <a href="#13" class="mim-tip-reference" title="Giglio, S., Broman, K. W., Matsumoto, N., Calvari, V., Gimelli, G., Neumann, T., Ohashi, H., Voullaire, L., Larizza, D., Giorda, R., Weber, J. L., Ledbetter, D. H., Zuffardi, O. &lt;strong&gt;Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.&lt;/strong&gt; Am. J. Hum. Genet. 68: 874-883, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11231899/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11231899&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11231899[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/319506&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11231899">Giglio et al. (2001)</a> demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. Their findings prompted <a href="#14" class="mim-tip-reference" title="Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O. &lt;strong&gt;Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.&lt;/strong&gt; Am. J. Hum. Genet. 71: 276-285, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12058347/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12058347&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12058347[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/341610&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12058347">Giglio et al. (2002)</a> to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In 7 subjects (5 of whom represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, <a href="#14" class="mim-tip-reference" title="Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O. &lt;strong&gt;Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.&lt;/strong&gt; Am. J. Hum. Genet. 71: 276-285, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12058347/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12058347&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12058347[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/341610&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12058347">Giglio et al. (2002)</a> demonstrated that breakpoints fell within the 4p and 8p OR gene clusters. FISH experiments with bacterial artificial chromosome (BAC) probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all 5 mothers of the de novo subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12058347+11231899+11063731+11183188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To define the distinctive WHS phenotype, and to map its specific clinical manifestations, <a href="#51" class="mim-tip-reference" title="Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G. &lt;strong&gt;Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.&lt;/strong&gt; Am. J. Hum. Genet. 72: 590-597, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12563561/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12563561&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/367925&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12563561">Zollino et al. (2003)</a> studied a total of 8 patients carrying a 4p16.3 microdeletion. The extent of each deletion was established by FISH, with a cosmid contig spanning the entire genomic region from MSX1 (<a href="/entry/142983">142983</a>) in the distal half of 4p16.1 to the subtelomeric locus D4S3359. The deletions were 1.9-3.5 Mb, and all were terminal. All of the patients presented with a mild phenotype, in which major malformations were usually absent. Head circumference was normal for height in the 2 patients with the smallest deletions (1.9 and 2.2 Mb). The theretofore accepted WHS critical region, a 165-kb interval on 4p16.3 defined by the loci D4S166 and D4S3327 (<a href="#48" class="mim-tip-reference" title="Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R. &lt;strong&gt;A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.&lt;/strong&gt; Hum. Molec. Genet. 6: 317-324, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9063753/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9063753&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.2.317&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9063753">Wright et al., 1997</a>) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 to the telomere. Clinically, the distinctive WHS phenotype was defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype was found by <a href="#51" class="mim-tip-reference" title="Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G. &lt;strong&gt;Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.&lt;/strong&gt; Am. J. Hum. Genet. 72: 590-597, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12563561/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12563561&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/367925&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12563561">Zollino et al. (2003)</a> to map distal to the critical region accepted at that time. <a href="#51" class="mim-tip-reference" title="Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G. &lt;strong&gt;Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.&lt;/strong&gt; Am. J. Hum. Genet. 72: 590-597, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12563561/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12563561&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/367925&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12563561">Zollino et al. (2003)</a> proposed a new critical region for WHS, which they designated WHSCR2, as a 300- to 600-kb interval on 4p16.3 between D4S3327 and D4S98-D4S168, contiguous distally with the WHSCR defined by <a href="#48" class="mim-tip-reference" title="Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R. &lt;strong&gt;A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.&lt;/strong&gt; Hum. Molec. Genet. 6: 317-324, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9063753/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9063753&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.2.317&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9063753">Wright et al. (1997)</a>. Among the candidate genes already described for WHS, the authors considered LETM1 (<a href="/entry/604407">604407</a>) likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, they recommended dividing the WHS phenotype into 2 distinct clinical entities, a 'classical' and a 'mild' form. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9063753+12563561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Nieminen, P., Kotilainen, J., Aalto, Y., Knuutila, S., Pirinen, S., Thesleff, I. &lt;strong&gt;MSX1 gene is deleted in Wolf-Hirschhorn syndrome patients with oligodontia.&lt;/strong&gt; J. Dent. Res. 82: 1013-1017, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14630905/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14630905&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1177/154405910308201215&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14630905">Nieminen et al. (2003)</a> examined the dentition and the presence of the MSX1 (HOX7) gene (<a href="/entry/142983">142983</a>) in 8 Finnish patients with abnormalities of 4p, including 7 with WHS. Five of the WHS patients presented with agenesis of several teeth, suggesting that oligodontia may be a common, although previously not well-documented, feature of WHS. By FISH analysis, the 5 patients with oligodontia lacked 1 copy of MSX1, whereas the other 3 had both copies. One of patients in the latter group was the only one who had cleft palate. <a href="#28" class="mim-tip-reference" title="Nieminen, P., Kotilainen, J., Aalto, Y., Knuutila, S., Pirinen, S., Thesleff, I. &lt;strong&gt;MSX1 gene is deleted in Wolf-Hirschhorn syndrome patients with oligodontia.&lt;/strong&gt; J. Dent. Res. 82: 1013-1017, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14630905/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14630905&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1177/154405910308201215&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14630905">Nieminen et al. (2003)</a> concluded that haploinsufficiency for MSX1 serves as a mechanism that causes selective tooth agenesis but by itself is not sufficient to cause oral clefts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14630905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Van Buggenhout, G., Melotte, C., Dutta, B., Froyen, G., Van Hummelen, P., Marynen, P., Matthijs, G., de Ravel, T., Devriendt, K., Fryns, J. P., Vermeesch, J. R. &lt;strong&gt;Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map.&lt;/strong&gt; J. Med. Genet. 41: 691-698, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15342700/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15342700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2003.016865&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15342700">Van Buggenhout et al. (2004)</a> reported 6 patients with small deletions of chromosome 4p covering or flanking the WHS critical region, 5 of whom presented with mild phenotypic features of WHS. Two patients with small interstitial deletions allowed further refinement of the phenotypic map of the region. These analyses pinpointed hemizygosity of the WHSC1 (<a href="/entry/602952">602952</a>) gene as the cause of the typical WHS facial appearance. The results indicated that the other key features (microcephaly, cleft palate, and mental retardation) probably result from haploinsufficiency of more than 1 gene in the region and are thus true contiguous gene syndrome phenotypes. The breakpoints in the 3 terminal deletions identified in this study coincided with gaps in the human genome draft sequence. <a href="#38" class="mim-tip-reference" title="Van Buggenhout, G., Melotte, C., Dutta, B., Froyen, G., Van Hummelen, P., Marynen, P., Matthijs, G., de Ravel, T., Devriendt, K., Fryns, J. P., Vermeesch, J. R. &lt;strong&gt;Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map.&lt;/strong&gt; J. Med. Genet. 41: 691-698, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15342700/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15342700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2003.016865&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15342700">Van Buggenhout et al. (2004)</a> demonstrated that 1 of these gaps contains an olfactory receptor gene cluster, suggesting that low copy repeats not only mediate ectopic meiotic recombinations but are also susceptibility sites for terminal deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Rodriguez, L., Zollino, M., Climent, S., Mansilla, E., Lopez-Grondona, F., Martinez-Fernandez, M. L., Murdolo, M., Martinez-Frias, M. L. &lt;strong&gt;The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a second case.&lt;/strong&gt; Am. J. Med. Genet. 136A: 175-178, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15948183/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15948183&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30775&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15948183">Rodriguez et al. (2005)</a> reported a 4-year-old girl with a subtelomeric deletion of 4p16.3 who had a typical WHS facial appearance, growth and psychomotor delay, and 2 episodes of febrile seizures. FISH revealed that the 1.9-Mb deletion in this patient was from marker D4S3327 to the telomere, thus supporting the more distal WHS critical region (WHSCR2) proposed by <a href="#51" class="mim-tip-reference" title="Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G. &lt;strong&gt;Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.&lt;/strong&gt; Am. J. Hum. Genet. 72: 590-597, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12563561/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12563561&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/367925&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12563561">Zollino et al. (2003)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15948183+12563561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Maas, N. M. C., Van Buggenhout, G., Hannes, F., Thienpont, B., Sanlaville, D., Kok, K., Midro, A., Andrieux, J., Anderlid, B.-M., Schoumans, J., Hordijk, R., Devriendt, K., Fryns, J.-P., Vermeesch, J. R. &lt;strong&gt;Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).&lt;/strong&gt; J. Med. Genet. 45: 71-80, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17873117/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17873117&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2007.052910&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17873117">Maas et al. (2008)</a> used high-resolution array comparative genomic hybridization to analyze DNA from 21 WHS patients with pure 4p deletions, including 8 with a cytogenetically visible deletion and 13 with a submicroscopic deletion. Eight patients had previously been reported. Six had classic terminal 4p deletions ranging in size from 1.9 to 30 Mb, but 1 patient with mild clinical features had a 1.4-Mb deletion, the smallest ever reported. Interstitial deletions were identified in 4 patients. By comparison of the phenotypes and deletions, <a href="#24" class="mim-tip-reference" title="Maas, N. M. C., Van Buggenhout, G., Hannes, F., Thienpont, B., Sanlaville, D., Kok, K., Midro, A., Andrieux, J., Anderlid, B.-M., Schoumans, J., Hordijk, R., Devriendt, K., Fryns, J.-P., Vermeesch, J. R. &lt;strong&gt;Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).&lt;/strong&gt; J. Med. Genet. 45: 71-80, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17873117/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17873117&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.2007.052910&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17873117">Maas et al. (2008)</a> positioned the genes causing microcephaly and growth retardation between 0.3 and 1.4 Mb in the 4pter region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17873117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="pathogenesis" class="mim-anchor"></a>
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#19" class="mim-tip-reference" title="Kerzendorfer, C., Hannes, F., Colnaghi, R., Abramowicz, I., Carpenter, G., Vermeesch, J. R., O&#x27;Driscoll, M. &lt;strong&gt;Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.&lt;/strong&gt; Hum. Molec. Genet. 21: 2181-2193, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22328085/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22328085&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/dds033&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22328085">Kerzendorfer et al. (2012)</a> studied 3 WHS patient cell lines with different deletions of chromosome 4p16. The cell lines showed variable deletion of the SLBP (<a href="/entry/602422">602422</a>) and/or NELFA (<a href="/entry/606026">606026</a>) genes, depending on the size of the deletion, as evidenced by protein expression studies. Both of these genes are involved in histone biogenesis. All patient cell lines showed delayed progression from S-phase to M-phase of the cell cycle as well as reduced levels of chromatin-associated histones after DNA replication compared to wildtype cells, consistent with underexpression of the SLBP and NELFA genes. This was associated with increased expression of the non-chromatin-associated histone chaperone H3 (see, e.g., HIST1H3A, <a href="/entry/602810">602810</a>). Patient cells also showed defective DNA replication and enhanced sensitivity to camptothecin, which induces double-strand DNA breaks. The findings provided a mechanism for altered cell-cycle progression and impaired DNA replication that may contribute to the clinical features of WHS, such as growth retardation and microcephaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22328085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="animalModel" class="mim-anchor"></a>
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In mice, the homologs of genes involved in WHS map to chromosome 5 in a region of conserved synteny with human 4p16.3. <a href="#27" class="mim-tip-reference" title="Naf, D., Wilson, L. A., Bergstrom, R. A., Smith, R. S., Goodwin, N. C., Verkerk, A., van Ommen, G. J., Ackerman, S. L., Frankel, W. L., Schimenti, J. C. &lt;strong&gt;Mouse models for the Wolf-Hirschhorn deletion syndrome.&lt;/strong&gt; Hum. Molec. Genet. 10: 91-98, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11152656/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11152656&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.2.91&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11152656">Naf et al. (2001)</a> generated and characterized 5 mouse lines bearing radiation-induced deletions spanning the WHSCR syntenic region. Similar to WHS patients, these animals were growth-retarded, susceptible to seizures, and showed midline (palate closure, tail kinks), craniofacial, and ocular anomalies (colobomas, corneal opacities). Other phenotypes included cerebellar hypoplasia and a shortened cerebral cortex. Expression of WHS-like traits was variable and influenced by strain background and deletion size. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11152656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Nimura, K., Ura, K., Shiratori, H., Ikawa, M., Okabe, M., Schwartz, R. J., Kaneda, Y. &lt;strong&gt;A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.&lt;/strong&gt; Nature 460: 287-291, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19483677/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19483677&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08086&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19483677">Nimura et al. (2009)</a> showed that the H3K36me3-specific histone methyltransferase Whsc1 (<a href="/entry/602952">602952</a>) functions in transcriptional regulation together with developmental transcription factors whose defects overlap with the human disease WHS. <a href="#29" class="mim-tip-reference" title="Nimura, K., Ura, K., Shiratori, H., Ikawa, M., Okabe, M., Schwartz, R. J., Kaneda, Y. &lt;strong&gt;A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.&lt;/strong&gt; Nature 460: 287-291, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19483677/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19483677&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08086&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19483677">Nimura et al. (2009)</a> found that mouse Whsc1, 1 of 5 putative Set2 homologs, governed H3K36me3 along euchromatin by associating with the cell type-specific transcription factors Sall1 (<a href="/entry/602218">602218</a>), Sall4 (<a href="/entry/607343">607343</a>), and Nanog (<a href="/entry/607937">607937</a>) in embryonic stem cells, and Nkx2-5 (<a href="/entry/600584">600584</a>) in embryonic hearts, regulating the expression of their target genes. Whsc1-deficient mice showed growth retardation and various WHS-like midline defects, including congenital cardiovascular anomalies. The effects of Whsc1 haploinsufficiency were increased in Nkx2-5 heterozygous mutant hearts, indicating their functional link. <a href="#29" class="mim-tip-reference" title="Nimura, K., Ura, K., Shiratori, H., Ikawa, M., Okabe, M., Schwartz, R. J., Kaneda, Y. &lt;strong&gt;A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.&lt;/strong&gt; Nature 460: 287-291, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19483677/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19483677&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08086&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19483677">Nimura et al. (2009)</a> proposed that WHSC1 functions together with developmental transcription factors to prevent the inappropriate transcription that can lead to various pathophysiologies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19483677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="McQuibban, A. G., Joza, N., Megighian, A., Scorzeto, M., Zanini, D., Reipert, S., Richter, C., Schweyen, R. J., Nowikovsky, K. &lt;strong&gt;A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome.&lt;/strong&gt; Hum. Molec. Genet. 19: 987-1000, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20026556/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20026556&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddp563&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20026556">McQuibban et al. (2010)</a> identified the Drosophila gene CG4589 as the ortholog of LETM1 (<a href="/entry/604407">604407</a>), which they considered a candidate gene for seizures seen in WHS. The authors assayed the effects of downregulating the CG4589 gene, which they renamed DmLETM1, on mitochondrial function in vivo and in vitro. Conditional inactivation of DmLETM1 function in specific tissues resulted in roughening of the adult eye, mitochondrial swelling, and developmental lethality in third-instar larvae, possibly the result of deregulated mitophagy. Neuronal-specific downregulation of DmLETM1 resulted in impairment of locomotor behavior in the fly and reduced synaptic neurotransmitter release. DmLETM1 complemented growth and mitochondrial K+/H+ exchange (KHE) activity in yeast deficient for LETM1. The authors proposed that DmLETM1 functions as a mitochondrial osmoregulator through its mitochondrial K+/H+ exchange activity and may explain part of the pathophysiologic WHS phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20026556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="history" class="mim-anchor"></a>
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#8" class="mim-tip-reference" title="de Die-Smulders, C. E. M., Engelen, J. J. M. &lt;strong&gt;11q duplication in a patient with Pitt-Rogers-Danks phenotype. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 66: 116-117, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8957528/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8957528&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;116::AID-AJMG30&gt;3.0.CO;2-T&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8957528">De Die-Smulders and Engelen (1996)</a> described a 50-year-old woman with kyphoscoliosis and typical clinical manifestations of Pitt syndrome who was found to have duplication of the segment 11q22-q23. Other family members were not karyotyped. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Lurie1980" class="mim-tip-reference" title="Lurie, I. W., Lazjuk, G. I., Ussova, Y. I., Presman, E. B., Gurevich, D. B. &lt;strong&gt;The Wolf-Hirschhorn syndrome. I. Genetics.&lt;/strong&gt; Clin. Genet. 17: 375-384, 1980.">Lurie et al. (1980)</a>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Altherr1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Altherr, M. R., Bengtsson, U., Elder, F. F. B., Ledbetter, D. H., Wasmuth, J. J., McDonald, M. E., Gusella, J. F., Greenberg, F.
<strong>Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4.</strong>
Am. J. Hum. Genet. 49: 1235-1242, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1746553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1746553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1746553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Anvret1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Anvret, M., Nordenskjold, M., Stolpe, L., Johansson, L., Brondum-Nielsen, K.
<strong>Molecular analysis of 4p deletion associated with Wolf-Hirschhorn syndrome moving the 'critical segment' towards the telomere.</strong>
Hum. Genet. 86: 481-483, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2016087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2016087</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2016087" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00194637" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Battaglia1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Battaglia, A., Carey, J. C., Cederholm, P., Viskochil, D. H., Brothman, A. R., Galasso, C.
<strong>Natural history of Wolf-Hirschhorn syndrome: experience with 15 cases.</strong>
Pediatrics 103: 830-836, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10103318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10103318</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10103318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1542/peds.103.4.830" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Battaglia1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Battaglia, A., Carey, J. C.
<strong>Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome. (Letter)</strong>
Am. J. Med. Genet. 75: 541 only, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489803</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980217)75:5&lt;541::aid-ajmg18&gt;3.0.co;2-k" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Battaglia2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Battaglia, A., Filippi, T., Carey, J. C.
<strong>Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.</strong>
Am. J. Med. Genet. C Semin. Med. Genet. 148C: 246-251, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18932224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18932224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18932224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.c.30187" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Clemens1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clemens, M., Martsolf, J. T., Rogers, J. G., Mowery-Rushton, P., Surti, U., McPherson, E.
<strong>Pitt-Rogers-Danks syndrome: the result of a 4p microdeletion.</strong>
Am. J. Med. Genet. 66: 95-100, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8957524/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8957524</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957524" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;95::AID-AJMG26&gt;3.0.CO;2-K" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Clemens1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clemens, M., McPherson, E. W., Surti, U.
<strong>4p microdeletion in a child with Pitt-Rogers-Danks syndrome. (Abstract)</strong>
Am. J. Hum. Genet. 57: A85 only, 1995.
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="de Die-Smulders1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
de Die-Smulders, C. E. M., Engelen, J. J. M.
<strong>11q duplication in a patient with Pitt-Rogers-Danks phenotype. (Letter)</strong>
Am. J. Med. Genet. 66: 116-117, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8957528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8957528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;116::AID-AJMG30&gt;3.0.CO;2-T" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Donnai1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Donnai, D.
<strong>A further patient with the Pitt-Rogers-Danks syndrome of mental retardation, unusual face, and intrauterine growth retardation.</strong>
Am. J. Med. Genet. 24: 29-32, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3706410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3706410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3706410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320240105" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Donnai1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Donnai, D.
<strong>Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 66: 101-103, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8957525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8957525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;101::AID-AJMG27&gt;3.0.CO;2-V" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Estabrooks1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Estabrooks, L. L., Lamb, A. N., Kirkman, H. N., Callanan, N. P., Rao, K. W.
<strong>A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.</strong>
Am. J. Hum. Genet. 51: 971-978, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1384329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1384329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1384329" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Gandelman1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gandelman, K.-Y., Gibson, L., Meyn, M. S., Yang-Feng, T. L.
<strong>Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome.</strong>
Am. J. Hum. Genet. 51: 571-578, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379774</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Giglio2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Giglio, S., Broman, K. W., Matsumoto, N., Calvari, V., Gimelli, G., Neumann, T., Ohashi, H., Voullaire, L., Larizza, D., Giorda, R., Weber, J. L., Ledbetter, D. H., Zuffardi, O.
<strong>Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.</strong>
Am. J. Hum. Genet. 68: 874-883, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11231899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11231899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11231899[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11231899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/319506" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Giglio2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O.
<strong>Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.</strong>
Am. J. Hum. Genet. 71: 276-285, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12058347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12058347</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12058347[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12058347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/341610" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Goodship1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goodship, J., Curtis, A., Cross, I., Brown, J., Emslie, J., Wolstenholme, J., Bhattacharya, S., Burn, J.
<strong>A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation.</strong>
J. Med. Genet. 29: 451-454, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1640422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1640422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1640422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Gusella1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gusella, J. F., Tanzi, R. E., Bader, P. I., Phelan, M. C., Stevenson, R., Hayden, M. R., Hofman, K. J., Faryniarz, A. G., Gibbons, K.
<strong>Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome.</strong>
Nature 318: 75-78, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2997623/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2997623</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2997623" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/318075a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Hirschhorn1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hirschhorn, K., Cooper, H. L., Firschein, I. L.
<strong>Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion.</strong>
Humangenetik 1: 479-482, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5895684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5895684</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5895684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00279124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Kant1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kant, S. G., Van Haeringen, A., Bakker, E., Stec, I., Donnai, D., Mollevanger, P., Beverstock, G. C., Lindeman-Kusse, M. C., Van Ommen, G.-J. B.
<strong>Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p16.3.</strong>
J. Med. Genet. 34: 569-572, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9222965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9222965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9222965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.7.569" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Kerzendorfer2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kerzendorfer, C., Hannes, F., Colnaghi, R., Abramowicz, I., Carpenter, G., Vermeesch, J. R., O'Driscoll, M.
<strong>Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.</strong>
Hum. Molec. Genet. 21: 2181-2193, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22328085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22328085</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22328085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/dds033" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Kurahashi2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kurahashi, H., Shaikh, T. H., Emanuel, B. S.
<strong>Alu-mediated PCR artifacts and the constitutional t(11;22) breakpoint.</strong>
Hum. Molec. Genet. 9: 2727-2732, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11063731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11063731</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11063731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/9.18.2727" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Lindeman-Kusse1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lindeman-Kusse, M. C., Van Haeringen, A., Hoorweg-Nijman, J. J. G., Brunner, H. G.
<strong>Cytogenetic abnormalities in two new patients with Pitt-Rogers-Dans phenotype.</strong>
Am. J. Med. Genet. 66: 104-112, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8957526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8957526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;104::AID-AJMG28&gt;3.0.CO;2-V" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Lizcano-Gil1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lizcano-Gil, L. A., Garcia-Cruz, D., Garcia-Cruz, O., Sanchez-Corona, J.
<strong>Pitt-Rogers-Danks syndrome: further delineation.</strong>
Am. J. Med. Genet. 55: 420-422, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320550407" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Lurie1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lurie, I. W., Lazjuk, G. I., Ussova, Y. I., Presman, E. B., Gurevich, D. B.
<strong>The Wolf-Hirschhorn syndrome. I. Genetics.</strong>
Clin. Genet. 17: 375-384, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7398109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7398109</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7398109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1980.tb00167.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Maas2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maas, N. M. C., Van Buggenhout, G., Hannes, F., Thienpont, B., Sanlaville, D., Kok, K., Midro, A., Andrieux, J., Anderlid, B.-M., Schoumans, J., Hordijk, R., Devriendt, K., Fryns, J.-P., Vermeesch, J. R.
<strong>Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).</strong>
J. Med. Genet. 45: 71-80, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17873117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17873117</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17873117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2007.052910" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="McKeown1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McKeown, C., Read, A. P., Dodge, A., Stecko, O., Mercer, A., Harris, R.
<strong>Wolf-Hirschhorn locus is distal to D4S10 on short arm of chromosome 4.</strong>
J. Med. Genet. 24: 410-412, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3612716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3612716</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3612716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.24.7.410" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="McQuibban2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McQuibban, A. G., Joza, N., Megighian, A., Scorzeto, M., Zanini, D., Reipert, S., Richter, C., Schweyen, R. J., Nowikovsky, K.
<strong>A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome.</strong>
Hum. Molec. Genet. 19: 987-1000, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20026556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20026556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20026556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddp563" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Naf2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Naf, D., Wilson, L. A., Bergstrom, R. A., Smith, R. S., Goodwin, N. C., Verkerk, A., van Ommen, G. J., Ackerman, S. L., Frankel, W. L., Schimenti, J. C.
<strong>Mouse models for the Wolf-Hirschhorn deletion syndrome.</strong>
Hum. Molec. Genet. 10: 91-98, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11152656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11152656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11152656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/10.2.91" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Nieminen2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nieminen, P., Kotilainen, J., Aalto, Y., Knuutila, S., Pirinen, S., Thesleff, I.
<strong>MSX1 gene is deleted in Wolf-Hirschhorn syndrome patients with oligodontia.</strong>
J. Dent. Res. 82: 1013-1017, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14630905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14630905</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14630905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1177/154405910308201215" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Nimura2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nimura, K., Ura, K., Shiratori, H., Ikawa, M., Okabe, M., Schwartz, R. J., Kaneda, Y.
<strong>A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.</strong>
Nature 460: 287-291, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19483677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19483677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19483677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/nature08086" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Oorthuys1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Oorthuys, J. W. E., Bleeker-Wagemakers, E. M.
<strong>A girl with the Pitt-Rogers-Danks syndrome.</strong>
Am. J. Med. Genet. 32: 140-141, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2705474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2705474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2705474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320320130" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Partington1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Partington, M. W., Fagan, K., Soubjaki, V., Turner, G.
<strong>Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome.</strong>
J. Med. Genet. 34: 719-728, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9321756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9321756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9321756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.9.719" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Pitt1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pitt, D. B., Rogers, J. G., Danks, D. M.
<strong>Mental retardation, unusual face, and intrauterine growth retardation: a new recessive syndrome?</strong>
Am. J. Med. Genet. 19: 307-313, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6542309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6542309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6542309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320190213" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Quarrell1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Quarrell, O. W. J., Snell, R. G., Curtis, M. A., Roberts, S. H., Harper, P. S., Shaw, D. J.
<strong>Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.</strong>
J. Med. Genet. 28: 256-259, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1856831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1856831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1856831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.4.256" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Rodriguez2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rodriguez, L., Zollino, M., Climent, S., Mansilla, E., Lopez-Grondona, F., Martinez-Fernandez, M. L., Murdolo, M., Martinez-Frias, M. L.
<strong>The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a second case.</strong>
Am. J. Med. Genet. 136A: 175-178, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15948183/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15948183</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15948183" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.30775" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Shannon2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shannon, N. L., Maltby, E. L., Rigby, A. S., Quarrell, O. W. J.
<strong>An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality.</strong>
J. Med. Genet. 38: 674-679, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11584045/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11584045</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11584045" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.38.10.674" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Tachdjian1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tachdjian, G., Fondacci, C., Tapia, S., Huten, Y., Blot, P., Nessmann, C.
<strong>The Wolf-Hirschhorn syndrome in fetuses.</strong>
Clin. Genet. 42: 281-287, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1493641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1493641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1493641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1992.tb03257.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Thies1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thies, U., Back, E., Wolff, G., Schroeder-Kurth, T., Hager, H.-D., Schroder, K.
<strong>Clinical, cytogenetic and molecular investigations in three patients with Wolf-Hirschhorn syndrome.</strong>
Clin. Genet. 42: 201-205, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1424245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1424245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1424245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1992.tb03238.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Van Buggenhout2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van Buggenhout, G., Melotte, C., Dutta, B., Froyen, G., Van Hummelen, P., Marynen, P., Matthijs, G., de Ravel, T., Devriendt, K., Fryns, J. P., Vermeesch, J. R.
<strong>Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map.</strong>
J. Med. Genet. 41: 691-698, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15342700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15342700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15342700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2003.016865" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Verbrugge2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Verbrugge, J., Choudhary, A. K., Ladda, R.
<strong>Tethered cord, corpus callosum abnormalities, and periventricular cysts in Wolf-Hirschhorn syndrome: Report of two cases and review of the literature.</strong>
Am. J. Med. Genet. 149A: 2280-2284, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19764025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19764025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.33022" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Wieczorek2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wieczorek, D., Krause, M., Majewski, F., Albrecht, B., Meinecke, P., Riess, O., Gillessen-Kaesbach, G.
<strong>Unexpected high frequency of de novo unbalanced translocations in patients with Wolf-Hirschhorn syndrome (WHS). (Letter)</strong>
J. Med. Genet. 37: 798-804, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11183188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11183188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11183188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.37.10.798" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Wieland2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wieland, I., Muschke, P., Wieacker, P.
<strong>Further delineation of Wittwer syndrome and refinement of the mapping region.</strong>
Am. J. Med. Genet. 116A: 57-60, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12476452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12476452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12476452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.10874" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Wieland2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wieland, I., Schanze, D., Schanze, I., Volleth, M., Muschke, P., Zenker, M.
<strong>A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. (Letter)</strong>
Am. J. Med. Genet. 164A: 3213-3214, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25251057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25251057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25251057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.36765" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Wittwer1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wittwer, B., Kircheisen, R., Leutelt, J., Orth, U., Gal, A.
<strong>New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.</strong>
Am. J. Med. Genet. 64: 42-49, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8826447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8826447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8826447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1&lt;42::AID-AJMG6&gt;3.0.CO;2-T" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Wolf1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wolf, U., Reinwein, H., Porsch, R., Schroter, R., Baitsch, H.
<strong>Defizienz an den kurzen Armen eines Chromosoms Nr. 4.</strong>
Humangenetik 1: 397-413, 1965.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5868696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5868696</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5868696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Worthington2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Worthington, J. C., Rigby, A. S., Quarrell, O. W.
<strong>Seizure frequency in adults with Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 146A: 2528-2531, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18792972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18792972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18792972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.32483" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="Wright1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wright, T. J., Altherr, M. R., Callen, D., Hirschhorn, K.
<strong>Reply to the letter to the editor by Partington and Turner--'Wolf-Hirschhorn and Pitt-Rogers-Danks syndrome'.</strong>
Am. J. Med. Genet. 82: 89-90, 1999.
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Wright1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wright, T. J., Clemens, M., Quarrell, O., Altherr, M. R.
<strong>Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes caused by overlapping 4p deletions.</strong>
Am. J. Med. Genet. 75: 345-350, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9482639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9482639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980203)75:4&lt;345::aid-ajmg2&gt;3.0.co;2-p" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Wright1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R.
<strong>A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.</strong>
Hum. Molec. Genet. 6: 317-324, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9063753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/6.2.317" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Zollino1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zollino, M., Bova, R., Neri, G.
<strong>From Pitt-Rogers-Danks syndrome to Wolf-Hirschhorn syndrome and back?</strong>
Am. J. Med. Genet. 66: 113-115, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8957527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8957527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8957527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;113::AID-AJMG29&gt;3.0.CO;2-U" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Zollino2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zollino, M., Di Stefano, C., Zampino, G., Mastroiacovo, P., Wright, T. J., Sorge, G., Selicorni, A., Tenconi, R., Zappala, A., Battaglia, A., Di Rocco, M., Palka, G., Pallotta, R., Altherr, M. R., Neri, G.
<strong>Genotype-phenotype correlations and clinical diagnostic criteria in Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 94: 254-261, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10995514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10995514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10995514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1096-8628(20000918)94:3&lt;254::aid-ajmg13&gt;3.0.co;2-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Zollino2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G.
<strong>Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.</strong>
Am. J. Hum. Genet. 72: 590-597, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12563561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12563561</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12563561[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12563561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/367925" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Carol A. Bocchini - updated : 3/10/2015
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 6/5/2013<br>George E. Tiller - updated : 11/10/2011<br>Cassandra L. Kniffin - updated : 10/14/2010<br>Carol A. Bocchini - updated : 6/10/2010<br>Ada Hamosh - updated : 8/27/2009<br>Cassandra L. Kniffin - updated : 4/15/2009<br>Cassandra L. Kniffin - updated : 8/18/2008<br>Marla J. F. O'Neill - updated : 12/28/2005<br>Gregory S. Antonarakis - updated : 8/9/2005<br>Victor A. McKusick - updated : 11/15/2004<br>Victor A. McKusick - updated : 10/12/2004<br>Victor A. McKusick - updated : 2/26/2003<br>Victor A. McKusick - updated : 8/16/2002<br>Michael J. Wright - updated : 7/30/2002<br>George E. Tiller - updated : 3/12/2001<br>Victor A. McKusick - updated : 10/4/2000<br>Victor A. McKusick - updated : 5/5/1999<br>Victor A. McKusick - updated : 7/8/1998<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 4/21/1997
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 10/1/1987
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 07/17/2017
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 03/11/2015<br>mcolton : 3/11/2015<br>carol : 3/10/2015<br>alopez : 6/7/2013<br>ckniffin : 6/5/2013<br>alopez : 11/16/2011<br>alopez : 11/16/2011<br>terry : 11/10/2011<br>wwang : 10/19/2010<br>ckniffin : 10/14/2010<br>carol : 9/29/2010<br>terry : 8/9/2010<br>carol : 6/10/2010<br>carol : 6/10/2010<br>alopez : 9/30/2009<br>alopez : 9/8/2009<br>terry : 8/27/2009<br>wwang : 5/7/2009<br>ckniffin : 4/15/2009<br>carol : 2/26/2009<br>carol : 2/25/2009<br>wwang : 8/20/2008<br>ckniffin : 8/18/2008<br>wwang : 12/29/2005<br>terry : 12/28/2005<br>carol : 8/11/2005<br>terry : 8/9/2005<br>tkritzer : 11/18/2004<br>terry : 11/15/2004<br>tkritzer : 10/14/2004<br>terry : 10/12/2004<br>carol : 5/28/2003<br>alopez : 2/27/2003<br>terry : 2/26/2003<br>terry : 11/22/2002<br>tkritzer : 8/23/2002<br>tkritzer : 8/21/2002<br>terry : 8/16/2002<br>tkritzer : 8/6/2002<br>tkritzer : 8/2/2002<br>tkritzer : 8/1/2002<br>terry : 7/30/2002<br>mcapotos : 6/21/2001<br>cwells : 3/27/2001<br>cwells : 3/12/2001<br>cwells : 3/7/2001<br>mcapotos : 10/5/2000<br>mcapotos : 10/5/2000<br>terry : 10/4/2000<br>carol : 5/10/1999<br>terry : 5/5/1999<br>carol : 8/7/1998<br>terry : 7/8/1998<br>mark : 2/24/1998<br>terry : 2/19/1998<br>terry : 2/19/1998<br>jenny : 4/21/1997<br>mark : 10/6/1995<br>mimadm : 6/7/1995<br>carol : 5/14/1993<br>carol : 5/11/1993<br>carol : 4/5/1993<br>carol : 2/3/1993
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 194190
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
WOLF-HIRSCHHORN SYNDROME; WHS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CHROMOSOME 4p16.3 DELETION SYNDROME<br />
PITT-ROGERS-DANKS SYNDROME; PRDS<br />
PITT SYNDROME<br />
WITTWER SYNDROME
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 17122004, 718226002; &nbsp;
<strong>ICD10CM:</strong> Q93.3; &nbsp;
<strong>ORPHA:</strong> 280; &nbsp;
<strong>DO:</strong> 0050460; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: 4p16.3
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : 4:1-4,500,000 </span>
</em>
</strong>
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene-Phenotype Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="1">
<span class="mim-font">
4p16.3
</span>
</td>
<td>
<span class="mim-font">
Wolf-Hirschhorn syndrome
</span>
</td>
<td>
<span class="mim-font">
194190
</span>
</td>
<td>
<span class="mim-font">
Isolated cases
</span>
</td>
<td>
<span class="mim-font">
4
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome associated with a hemizygous deletion of chromosome 4p16.3.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The Wolf-Hirschhorn syndrome is characterized by severe growth retardation and mental defect, microcephaly, 'Greek helmet' facies, and closure defects (cleft lip or palate, coloboma of the eye, and cardiac septal defects) (Hirschhorn et al., 1965; Wolf et al., 1965). </p><p>In 2 mentally retarded sisters and 2 other unrelated patients (1 male, 1 female), Pitt et al. (1984) reported a seemingly distinctive syndrome: intrauterine growth retardation with subsequent dwarfism, and unusual, characteristic facies. Short upper lip, prominent and slanting eyes, telecanthus, wide mouth, and microcephaly were described. Donnai (1986) and Oorthuys and Bleeker-Wagemakers (1989) described single similar cases. Lizcano-Gil et al. (1995) described a similar case of what was then called the 'Pitt-Rogers-Danks syndrome (PRDS)' or 'Pitt syndrome,' with the additional feature of optic atrophy. The father was 37 years old, prompting Lizcano-Gil et al. (1995) to suggest new dominant mutation with paternal age effect. Clemens et al. (1995, 1996) described a patient thought to have Pitt syndrome in whom fluorescence in situ hybridization analysis using the D4S96 probe specific for the WHS region at 4p16.3 revealed microdeletion in 20 of 20 metaphase cells tested. Donnai (1996) and Lindeman-Kusse et al. (1996) also found microdeletions of 4p16.3 in 4 patients previously diagnosed as having Pitt syndrome. Moreover, 2 sisters originally reported by Pitt et al. (1984) showed 46,XX,-4 +der 4 t(4;8)(p16.3;p23.1) pat. Although Donnai (1996) and Zollino et al. (1996) noted that 4p deletions had not been demonstrated in all cases of Pitt syndrome, the possibility remained that these cases had small deletions within the critical WHS region. </p><p>Wittwer et al. (1996) reported a family in which 3 males related as first cousins through carrier sisters were thought to have a novel X-linked mental retardation syndrome. Typical features included prenatal and severe postnatal growth retardation, blindness due to microphthalmia or optic atrophy, moderate to severe hearing loss, dysmorphic features, epilepsy, and severe mental retardation with absence of speech. Urogenital anomalies, malrotation of the gut, and abnormal segmentation of the lungs were also observed. Wieland et al. (2003) restudied this family and concluded that there were also typical skeletal changes. In 1 patient, radiographic examination showed dysplastic lesions in the proximal femurs and the vertebrae. These lesions were progressive and were assumed to be present in another patient because osteochondroma-like changes were mentioned in clinical reports. The patients never achieved walking. They also had white hair in early childhood, which contrasted with the hair color of their relatives. Haplotype analysis and investigation with microsatellite and EST markers suggested a disease locus in a region of Xp22, but no evidence for deletion indicative of a contiguous gene deletion syndrome was found. In a clinical and genetic reevaluation of the 2 living affected sibs in this family, Wieland et al. (2014) concluded that the disorder, previously called Wittwer syndrome, is a variant of Wolf-Hirschhorn syndrome (see CYTOGENETICS). </p><p>Kant et al. (1997) studied the patients with Pitt syndrome reported by Lindeman-Kusse et al. (1996) and Oorthuys and Bleeker-Wagemakers (1989) as well as an additional patient. They demonstrated that in each case there was a deletion of 4p16 that overlapped and extended beyond the WHS critical region in each direction. The minimal deleted region in these 4 patients extended from D4S126 to the telomere, with the largest deletion being from D4S394 to the telomere. As a result of their study, Kant et al. (1997) considered it likely that the Pitt and Wolf-Hirschhorn syndromes result from deletion in the same region of 4p16. </p><p>Wright et al. (1998) came to a similar conclusion from analysis of a patient with WHS and 2 patients with PRDS. They analyzed the patients at the molecular level, using a series of cosmids across a 4.5-Mb region of 4p16.3. They found that the molecular defects associated with the 2 syndromes show considerable overlap. They concluded that the 2 conditions result from the absence of similar, if not identical, genetic segments and proposed that the clinical differences observed between them are likely the result of allelic variation in the remaining homolog. Battaglia and Carey (1998) also argued that the Pitt-Rogers-Danks syndrome is essentially the same as Wolf-Hirschhorn syndrome, i.e., a 4p deletion syndrome. Wright et al. (1999) further defended the conclusion that WHS and PRDS represent clinical variation of a single disorder. They concluded that WHS and PRDS should no longer be considered separately but instead referred to as WHS (the original name). The prognosis for patients will be determined by the range and severity of symptoms present in the individual cases. </p><p>Battaglia et al. (1999) evaluated 15 patients with the 4p- syndrome (12 females, 3 males) in 3 centers. Follow-up spanning 16 years was achieved in 4 of the cases. Thirteen cases were detected by cytogenetics (regular G-banding in 10; high-resolution banding in 3), while the remaining 2 required fluorescence in situ hybridization. Of the 15 patients, 5 (33.3%) had heart lesions; 7 (47%) had orofacial clefts; 13 (87%) had a seizure disorder that tended to disappear with age; and all 15 had severe/profound developmental retardation. One Italian patient had sensorineural deafness and 1 Utah patient had a right split-hand defect. Of note, 2 Utah patients were able to walk with support (at 4 and 12 years of age, respectively), whereas 3 Italian patients and 1 Utah patient were able to walk unassisted (at 4, 5, 5 years 9 months, and 7 years of age, respectively). Two of the 3 Italian patients also achieved sphincter control by day. Eight patients receiving serial electroencephalogram studies showed fairly distinctive abnormalities, usually outlasting seizures. A slow, but constant progress in development was observed in all cases during the follow-up period. </p><p>Shannon et al. (2001) reported a study of 159 cases of WHS. Of the 146 cases in which it was possible to collect status, 96 were alive, 37 had died, and 13 were detected on prenatal diagnostic tests. The authors estimated a minimum birth incidence of 1 in 95,896. The crude infant mortality rate was 23 of 132 (17%), and in the first 2 years of life the mortality rate was 28 of 132 (21%). Cases with large de novo deletions (proximal to and including p15.2) were more likely to have died than those with smaller deletions (odds ratio = 5.7; 95% confidence interval 1.7 to 19.9). A comparison of the survival curves for de novo deletions and translocations did not show a statistically significant difference. Shannon et al. (2001) concluded that the mortality rate for WHS was lower than previously reported and that there was a statistically significant relationship between deletion size and overall risk of death in de novo deletion cases. </p><p>By telephone survey of 27 adults with WHS ranging in age from 17 to 40 years and their parents, Worthington et al. (2008) found that most patients had cessation of seizures in childhood. A seizure had not occurred in 3 years in 18 (66%) patients, and the mean age of the last seizure in those who were seizure-free was 11.3 years. In addition, many parents commented that seizures were triggered by fever. Worthington et al. (2008) noted that these findings may have relevance in genetic counseling. </p><p>Verbrugge et al. (2009) reported 2 unrelated patients with genetically confirmed WHS associated with growth retardation, craniofacial abnormalities, heart defects, and other anomalies. MRI showed tethered spinal cord in both patients. A literature review of 22 reports of neuroimaging findings in WHS indicated that the most common findings were corpus callosum abnormalities (71%), focal white matter signal abnormalities (46%), lateral and third ventricle enlargement (42%), white matter volume reductions (42%), and periventricular cysts (29%). Periventricular cysts were associated with the first year of life, but then appeared to fuse with the frontal horns during late infancy with enlargement of the frontal horns. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Tachdjian et al. (1992) described prenatal diagnosis of 5 cases of WHS studied because of severe intrauterine growth retardation detected on routine ultrasound. At autopsy, the fetuses showed typical craniofacial dysmorphia without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were found in all, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias, and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. Delayed bone age was present in all. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The frequency of Wolf-Hirschhorn syndrome is estimated at 1/20,000 to 1/50,000 births, with a female predilection of 2:1 (Battaglia et al., 1999; Maas et al., 2008). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Cytogenetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The critical zone for development of WHS is located distal to the Huntington disease-linked G8 (D4S10) marker. Although Gusella et al. (1985) found apparent deletion of D4S10 when they tested 7 unrelated patients with WHS, McKeown et al. (1987) reported a family in which 2 children with WHS retained the D4S10 locus on the deleted chromosome. WHS in the 2 sibs was the result of unbalanced segregation of a reciprocal 4;12 translocation in the mother. </p><p>Altherr et al. (1991) described a molecular deletion in 4p due to a subtle, inherited translocation between chromosomes 4 and 19, leading to the Wolf-Hirschhorn syndrome phenotype. </p><p>Gandelman et al. (1992) described a subtle deletion of 4p in a patient with WHS. Using probes from 4p16.3, they demonstrated a deletion of approximately 2.5 Mb with the breakpoint located approximately 80 kb distal to D4S43. </p><p>In 7 cases of WHS, Quarrell et al. (1991) found that there was de novo deletion or rearrangement of 4p; in each case the abnormality had arisen on the paternal chromosome. A paternal age effect was not observed, however. </p><p>Anvret et al. (1991) reported molecular studies in 2 patients with WHS which showed that the critical region was within 4p16.3. The deletion was of maternal origin in one patient and of paternal origin in the other. </p><p>Goodship et al. (1992) described a 2-year-old girl who presented with developmental delay and subtle dysmorphic features suggesting Wolf-Hirschhorn syndrome: hypertelorism, prominent glabella, short philtrum, and carp-shaped mouth. Although high resolution chromosome analysis was normal in the child and in both parents, molecular analysis indicated that the child had not inherited a maternal allele of probes from 4p16. Prenatal diagnosis in the next pregnancy showed that again the fetus had no maternal allele for probes mapping to 4p16. Fluorescence in situ hybridization (FISH) in the mother showed a submicroscopic translocation between chromosomes 4 and 10. </p><p>Estabrooks et al. (1992) reported 2 families with a satellited chromosome 4 short arm. Satellites and stalks normally occur on the short arms of acrocentric chromosomes. Although satellited nonacrocentric chromosomes, presumably resulting through translocation from an acrocentric chromosome, had been reported, this was the first report of involvement of 4p. By Southern blot analysis and FISH, deletion of material mapping approximately 150 kb from 4pter was discovered. Notably, the phenotype was normal with no signs of WHS. Estabrooks et al. (1992) speculated that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement. </p><p>Thies et al. (1992) reported 3 apparently de novo deletion cases of WHS. Molecular studies indicated that the deleted segment was of paternal origin in 2 and maternal in the other. </p><p>Partington et al. (1997) reported individuals from 3 families in which there was a translocation involving 4p16.3. Nine individuals had clinical features of Pitt syndrome, and a deletion of 4p16.3 was shown by fluorescence in situ hybridization analysis in all 8 patients so studied. Eleven patients had a 'new' syndrome consisting of overgrowth with heavy facial features and mild to moderate mental retardation. A duplication of 4p16.3 was found in the 4 subjects studied. Partington et al. (1997) suggested that the growth abnormalities in these 2 families could be explained by a dosage effect of the FGFR3 gene (134934), with a single dose leading to growth failure and a triple dose to physical overgrowth. </p><p>Wright et al. (1997) presented a transcript map of the WHS critical region (WHSCR1), an approximately 165 kb region (about 2 Mb from the telomere, defined by D4S166 and D4S3327) that is gene dense. </p><p>Zollino et al. (2003) proposed a new critical region for WHS, a 300- to 600-kb interval on 4p16.3 between D4S3327 and D4S98-D4S168 (WHSCR2; at 1.9 Mb from the telomere), contiguous distally with the WHSCR1 defined by Wright et al. (1997). </p><p>Wieland et al. (2014) reevaluated the 2 living males from the family reported by Wittwer et al. (1996) and Wieland et al. (2003) in which 3 males related as first cousins through carrier sisters were thought to have a novel X-linked mental retardation syndrome. Array-based molecular karyotyping revealed a cryptic genomic rearrangement in both patients involving deletion of about 8.4 Mb on 4p16.3p16.1 and duplication of about 3.9 Mb on 17q25.3. FISH confirmed the array results and identified the derivative chromosome der(4)t(4;17) in the patients and the balanced translocation in both female carriers. Wieland et al. (2014) noted that the key features of the patients met the description of WHS, including variable additional manifestations that may be explained in part by the size of the deletion in 4p16.3. They concluded that the disorder in this family, previously called Wittwer syndrome, falls within the phenotypic and genotypic spectrum of WHS. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Zollino et al. (2000) reported the findings in 16 WHS patients. In 11 patients, hemizygosity of 4p16.3 was detected by conventional prometaphase chromosome analysis; in 4 patients, it was detected by molecular probes on apparently normal chromosomes. One patient had normal chromosomes without a detectable molecular deletion within the WHS critical region. In each patient with a deletion, the deletion was demonstrated to be terminal by FISH. The proximal breakpoint of the rearrangement was established by prometaphase chromosome analysis in cases with a visible deletion. The breakpoint was within the 4p16.1 band in 6 patients, apparently coincident with the distal half of this band in 5 patients. The authors used a set of overlapping cosmid clones spanning the 4p16.3 region to establish the extent of each of the 4 submicroscopic deletions. Variations were found in both the size of the deletions and the position of the breakpoints. The precise definition of the cytogenetic defect permitted an analysis of genotype/phenotype correlations in WHS, leading to the proposal of a set of minimal diagnostic criteria. Deletion of less than 3.5 Mb resulted in a mild phenotype, in which malformations were absent. The absence of a detectable molecular deletion was still consistent with the diagnosis of WHS. Based on these observations, a 'minimal' WHS phenotype was inferred, the clinical manifestations of which are restricted to the typical facial appearance, mild mental and growth retardation, and congenital hypotonia. </p><p>The t(4;8)(p16;p23) translocation, in either the balanced or unbalanced form, has been reported several times (Wieczorek et al., 2000). Giglio et al. (2002) considered that the t(4;8)(p16;p23) translocation may be undetected in routine cytogenetics, and suggested that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans (Kurahashi et al., 2000; see 609029). Giglio et al. (2002) showed that subjects with der(4) had WHS, whereas subjects with der(8) showed a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR) gene clusters are located close to each other, on both 4p16 and 8p23. Giglio et al. (2001) demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. Their findings prompted Giglio et al. (2002) to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In 7 subjects (5 of whom represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, Giglio et al. (2002) demonstrated that breakpoints fell within the 4p and 8p OR gene clusters. FISH experiments with bacterial artificial chromosome (BAC) probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all 5 mothers of the de novo subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. </p><p>To define the distinctive WHS phenotype, and to map its specific clinical manifestations, Zollino et al. (2003) studied a total of 8 patients carrying a 4p16.3 microdeletion. The extent of each deletion was established by FISH, with a cosmid contig spanning the entire genomic region from MSX1 (142983) in the distal half of 4p16.1 to the subtelomeric locus D4S3359. The deletions were 1.9-3.5 Mb, and all were terminal. All of the patients presented with a mild phenotype, in which major malformations were usually absent. Head circumference was normal for height in the 2 patients with the smallest deletions (1.9 and 2.2 Mb). The theretofore accepted WHS critical region, a 165-kb interval on 4p16.3 defined by the loci D4S166 and D4S3327 (Wright et al., 1997) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 to the telomere. Clinically, the distinctive WHS phenotype was defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype was found by Zollino et al. (2003) to map distal to the critical region accepted at that time. Zollino et al. (2003) proposed a new critical region for WHS, which they designated WHSCR2, as a 300- to 600-kb interval on 4p16.3 between D4S3327 and D4S98-D4S168, contiguous distally with the WHSCR defined by Wright et al. (1997). Among the candidate genes already described for WHS, the authors considered LETM1 (604407) likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, they recommended dividing the WHS phenotype into 2 distinct clinical entities, a 'classical' and a 'mild' form. </p><p>Nieminen et al. (2003) examined the dentition and the presence of the MSX1 (HOX7) gene (142983) in 8 Finnish patients with abnormalities of 4p, including 7 with WHS. Five of the WHS patients presented with agenesis of several teeth, suggesting that oligodontia may be a common, although previously not well-documented, feature of WHS. By FISH analysis, the 5 patients with oligodontia lacked 1 copy of MSX1, whereas the other 3 had both copies. One of patients in the latter group was the only one who had cleft palate. Nieminen et al. (2003) concluded that haploinsufficiency for MSX1 serves as a mechanism that causes selective tooth agenesis but by itself is not sufficient to cause oral clefts. </p><p>Van Buggenhout et al. (2004) reported 6 patients with small deletions of chromosome 4p covering or flanking the WHS critical region, 5 of whom presented with mild phenotypic features of WHS. Two patients with small interstitial deletions allowed further refinement of the phenotypic map of the region. These analyses pinpointed hemizygosity of the WHSC1 (602952) gene as the cause of the typical WHS facial appearance. The results indicated that the other key features (microcephaly, cleft palate, and mental retardation) probably result from haploinsufficiency of more than 1 gene in the region and are thus true contiguous gene syndrome phenotypes. The breakpoints in the 3 terminal deletions identified in this study coincided with gaps in the human genome draft sequence. Van Buggenhout et al. (2004) demonstrated that 1 of these gaps contains an olfactory receptor gene cluster, suggesting that low copy repeats not only mediate ectopic meiotic recombinations but are also susceptibility sites for terminal deletions. </p><p>Rodriguez et al. (2005) reported a 4-year-old girl with a subtelomeric deletion of 4p16.3 who had a typical WHS facial appearance, growth and psychomotor delay, and 2 episodes of febrile seizures. FISH revealed that the 1.9-Mb deletion in this patient was from marker D4S3327 to the telomere, thus supporting the more distal WHS critical region (WHSCR2) proposed by Zollino et al. (2003). </p><p>Maas et al. (2008) used high-resolution array comparative genomic hybridization to analyze DNA from 21 WHS patients with pure 4p deletions, including 8 with a cytogenetically visible deletion and 13 with a submicroscopic deletion. Eight patients had previously been reported. Six had classic terminal 4p deletions ranging in size from 1.9 to 30 Mb, but 1 patient with mild clinical features had a 1.4-Mb deletion, the smallest ever reported. Interstitial deletions were identified in 4 patients. By comparison of the phenotypes and deletions, Maas et al. (2008) positioned the genes causing microcephaly and growth retardation between 0.3 and 1.4 Mb in the 4pter region. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Kerzendorfer et al. (2012) studied 3 WHS patient cell lines with different deletions of chromosome 4p16. The cell lines showed variable deletion of the SLBP (602422) and/or NELFA (606026) genes, depending on the size of the deletion, as evidenced by protein expression studies. Both of these genes are involved in histone biogenesis. All patient cell lines showed delayed progression from S-phase to M-phase of the cell cycle as well as reduced levels of chromatin-associated histones after DNA replication compared to wildtype cells, consistent with underexpression of the SLBP and NELFA genes. This was associated with increased expression of the non-chromatin-associated histone chaperone H3 (see, e.g., HIST1H3A, 602810). Patient cells also showed defective DNA replication and enhanced sensitivity to camptothecin, which induces double-strand DNA breaks. The findings provided a mechanism for altered cell-cycle progression and impaired DNA replication that may contribute to the clinical features of WHS, such as growth retardation and microcephaly. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In mice, the homologs of genes involved in WHS map to chromosome 5 in a region of conserved synteny with human 4p16.3. Naf et al. (2001) generated and characterized 5 mouse lines bearing radiation-induced deletions spanning the WHSCR syntenic region. Similar to WHS patients, these animals were growth-retarded, susceptible to seizures, and showed midline (palate closure, tail kinks), craniofacial, and ocular anomalies (colobomas, corneal opacities). Other phenotypes included cerebellar hypoplasia and a shortened cerebral cortex. Expression of WHS-like traits was variable and influenced by strain background and deletion size. </p><p>Nimura et al. (2009) showed that the H3K36me3-specific histone methyltransferase Whsc1 (602952) functions in transcriptional regulation together with developmental transcription factors whose defects overlap with the human disease WHS. Nimura et al. (2009) found that mouse Whsc1, 1 of 5 putative Set2 homologs, governed H3K36me3 along euchromatin by associating with the cell type-specific transcription factors Sall1 (602218), Sall4 (607343), and Nanog (607937) in embryonic stem cells, and Nkx2-5 (600584) in embryonic hearts, regulating the expression of their target genes. Whsc1-deficient mice showed growth retardation and various WHS-like midline defects, including congenital cardiovascular anomalies. The effects of Whsc1 haploinsufficiency were increased in Nkx2-5 heterozygous mutant hearts, indicating their functional link. Nimura et al. (2009) proposed that WHSC1 functions together with developmental transcription factors to prevent the inappropriate transcription that can lead to various pathophysiologies. </p><p>McQuibban et al. (2010) identified the Drosophila gene CG4589 as the ortholog of LETM1 (604407), which they considered a candidate gene for seizures seen in WHS. The authors assayed the effects of downregulating the CG4589 gene, which they renamed DmLETM1, on mitochondrial function in vivo and in vitro. Conditional inactivation of DmLETM1 function in specific tissues resulted in roughening of the adult eye, mitochondrial swelling, and developmental lethality in third-instar larvae, possibly the result of deregulated mitophagy. Neuronal-specific downregulation of DmLETM1 resulted in impairment of locomotor behavior in the fly and reduced synaptic neurotransmitter release. DmLETM1 complemented growth and mitochondrial K+/H+ exchange (KHE) activity in yeast deficient for LETM1. The authors proposed that DmLETM1 functions as a mitochondrial osmoregulator through its mitochondrial K+/H+ exchange activity and may explain part of the pathophysiologic WHS phenotype. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>De Die-Smulders and Engelen (1996) described a 50-year-old woman with kyphoscoliosis and typical clinical manifestations of Pitt syndrome who was found to have duplication of the segment 11q22-q23. Other family members were not karyotyped. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Lurie et al. (1980)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Altherr, M. R., Bengtsson, U., Elder, F. F. B., Ledbetter, D. H., Wasmuth, J. J., McDonald, M. E., Gusella, J. F., Greenberg, F.
<strong>Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4.</strong>
Am. J. Hum. Genet. 49: 1235-1242, 1991.
[PubMed: 1746553]
</p>
</li>
<li>
<p class="mim-text-font">
Anvret, M., Nordenskjold, M., Stolpe, L., Johansson, L., Brondum-Nielsen, K.
<strong>Molecular analysis of 4p deletion associated with Wolf-Hirschhorn syndrome moving the &#x27;critical segment&#x27; towards the telomere.</strong>
Hum. Genet. 86: 481-483, 1991.
[PubMed: 2016087]
[Full Text: https://doi.org/10.1007/BF00194637]
</p>
</li>
<li>
<p class="mim-text-font">
Battaglia, A., Carey, J. C., Cederholm, P., Viskochil, D. H., Brothman, A. R., Galasso, C.
<strong>Natural history of Wolf-Hirschhorn syndrome: experience with 15 cases.</strong>
Pediatrics 103: 830-836, 1999.
[PubMed: 10103318]
[Full Text: https://doi.org/10.1542/peds.103.4.830]
</p>
</li>
<li>
<p class="mim-text-font">
Battaglia, A., Carey, J. C.
<strong>Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome. (Letter)</strong>
Am. J. Med. Genet. 75: 541 only, 1998.
[PubMed: 9489803]
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980217)75:5&lt;541::aid-ajmg18&gt;3.0.co;2-k]
</p>
</li>
<li>
<p class="mim-text-font">
Battaglia, A., Filippi, T., Carey, J. C.
<strong>Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision.</strong>
Am. J. Med. Genet. C Semin. Med. Genet. 148C: 246-251, 2008.
[PubMed: 18932224]
[Full Text: https://doi.org/10.1002/ajmg.c.30187]
</p>
</li>
<li>
<p class="mim-text-font">
Clemens, M., Martsolf, J. T., Rogers, J. G., Mowery-Rushton, P., Surti, U., McPherson, E.
<strong>Pitt-Rogers-Danks syndrome: the result of a 4p microdeletion.</strong>
Am. J. Med. Genet. 66: 95-100, 1996.
[PubMed: 8957524]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;95::AID-AJMG26&gt;3.0.CO;2-K]
</p>
</li>
<li>
<p class="mim-text-font">
Clemens, M., McPherson, E. W., Surti, U.
<strong>4p microdeletion in a child with Pitt-Rogers-Danks syndrome. (Abstract)</strong>
Am. J. Hum. Genet. 57: A85 only, 1995.
</p>
</li>
<li>
<p class="mim-text-font">
de Die-Smulders, C. E. M., Engelen, J. J. M.
<strong>11q duplication in a patient with Pitt-Rogers-Danks phenotype. (Letter)</strong>
Am. J. Med. Genet. 66: 116-117, 1996.
[PubMed: 8957528]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;116::AID-AJMG30&gt;3.0.CO;2-T]
</p>
</li>
<li>
<p class="mim-text-font">
Donnai, D.
<strong>A further patient with the Pitt-Rogers-Danks syndrome of mental retardation, unusual face, and intrauterine growth retardation.</strong>
Am. J. Med. Genet. 24: 29-32, 1986.
[PubMed: 3706410]
[Full Text: https://doi.org/10.1002/ajmg.1320240105]
</p>
</li>
<li>
<p class="mim-text-font">
Donnai, D.
<strong>Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 66: 101-103, 1996.
[PubMed: 8957525]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;101::AID-AJMG27&gt;3.0.CO;2-V]
</p>
</li>
<li>
<p class="mim-text-font">
Estabrooks, L. L., Lamb, A. N., Kirkman, H. N., Callanan, N. P., Rao, K. W.
<strong>A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.</strong>
Am. J. Hum. Genet. 51: 971-978, 1992.
[PubMed: 1384329]
</p>
</li>
<li>
<p class="mim-text-font">
Gandelman, K.-Y., Gibson, L., Meyn, M. S., Yang-Feng, T. L.
<strong>Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome.</strong>
Am. J. Hum. Genet. 51: 571-578, 1992.
[PubMed: 1379774]
</p>
</li>
<li>
<p class="mim-text-font">
Giglio, S., Broman, K. W., Matsumoto, N., Calvari, V., Gimelli, G., Neumann, T., Ohashi, H., Voullaire, L., Larizza, D., Giorda, R., Weber, J. L., Ledbetter, D. H., Zuffardi, O.
<strong>Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements.</strong>
Am. J. Hum. Genet. 68: 874-883, 2001.
[PubMed: 11231899]
[Full Text: https://doi.org/10.1086/319506]
</p>
</li>
<li>
<p class="mim-text-font">
Giglio, S., Calvari, V., Gregato, G., Gimelli, G., Camanini, S., Giorda, R., Ragusa, A., Guerneri, S., Selicorni, A., Stumm, M., Tonnies, H., Ventura, M., Zollino, M., Neri, G., Barber, J., Wieczorek, D., Rocchi, M., Zuffardi, O.
<strong>Heterozygous submicroscopic inversions involving olfactory receptor--gene clusters mediate the recurrent t(4;8)(p16;p23) translocation.</strong>
Am. J. Hum. Genet. 71: 276-285, 2002.
[PubMed: 12058347]
[Full Text: https://doi.org/10.1086/341610]
</p>
</li>
<li>
<p class="mim-text-font">
Goodship, J., Curtis, A., Cross, I., Brown, J., Emslie, J., Wolstenholme, J., Bhattacharya, S., Burn, J.
<strong>A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation.</strong>
J. Med. Genet. 29: 451-454, 1992.
[PubMed: 1640422]
</p>
</li>
<li>
<p class="mim-text-font">
Gusella, J. F., Tanzi, R. E., Bader, P. I., Phelan, M. C., Stevenson, R., Hayden, M. R., Hofman, K. J., Faryniarz, A. G., Gibbons, K.
<strong>Deletion of Huntington&#x27;s disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome.</strong>
Nature 318: 75-78, 1985.
[PubMed: 2997623]
[Full Text: https://doi.org/10.1038/318075a0]
</p>
</li>
<li>
<p class="mim-text-font">
Hirschhorn, K., Cooper, H. L., Firschein, I. L.
<strong>Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion.</strong>
Humangenetik 1: 479-482, 1965.
[PubMed: 5895684]
[Full Text: https://doi.org/10.1007/BF00279124]
</p>
</li>
<li>
<p class="mim-text-font">
Kant, S. G., Van Haeringen, A., Bakker, E., Stec, I., Donnai, D., Mollevanger, P., Beverstock, G. C., Lindeman-Kusse, M. C., Van Ommen, G.-J. B.
<strong>Pitt-Rogers-Danks syndrome and Wolf-Hirschhorn syndrome are caused by a deletion in the same region on chromosome 4p16.3.</strong>
J. Med. Genet. 34: 569-572, 1997.
[PubMed: 9222965]
[Full Text: https://doi.org/10.1136/jmg.34.7.569]
</p>
</li>
<li>
<p class="mim-text-font">
Kerzendorfer, C., Hannes, F., Colnaghi, R., Abramowicz, I., Carpenter, G., Vermeesch, J. R., O'Driscoll, M.
<strong>Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.</strong>
Hum. Molec. Genet. 21: 2181-2193, 2012.
[PubMed: 22328085]
[Full Text: https://doi.org/10.1093/hmg/dds033]
</p>
</li>
<li>
<p class="mim-text-font">
Kurahashi, H., Shaikh, T. H., Emanuel, B. S.
<strong>Alu-mediated PCR artifacts and the constitutional t(11;22) breakpoint.</strong>
Hum. Molec. Genet. 9: 2727-2732, 2000.
[PubMed: 11063731]
[Full Text: https://doi.org/10.1093/hmg/9.18.2727]
</p>
</li>
<li>
<p class="mim-text-font">
Lindeman-Kusse, M. C., Van Haeringen, A., Hoorweg-Nijman, J. J. G., Brunner, H. G.
<strong>Cytogenetic abnormalities in two new patients with Pitt-Rogers-Dans phenotype.</strong>
Am. J. Med. Genet. 66: 104-112, 1996.
[PubMed: 8957526]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;104::AID-AJMG28&gt;3.0.CO;2-V]
</p>
</li>
<li>
<p class="mim-text-font">
Lizcano-Gil, L. A., Garcia-Cruz, D., Garcia-Cruz, O., Sanchez-Corona, J.
<strong>Pitt-Rogers-Danks syndrome: further delineation.</strong>
Am. J. Med. Genet. 55: 420-422, 1995.
[PubMed: 7762580]
[Full Text: https://doi.org/10.1002/ajmg.1320550407]
</p>
</li>
<li>
<p class="mim-text-font">
Lurie, I. W., Lazjuk, G. I., Ussova, Y. I., Presman, E. B., Gurevich, D. B.
<strong>The Wolf-Hirschhorn syndrome. I. Genetics.</strong>
Clin. Genet. 17: 375-384, 1980.
[PubMed: 7398109]
[Full Text: https://doi.org/10.1111/j.1399-0004.1980.tb00167.x]
</p>
</li>
<li>
<p class="mim-text-font">
Maas, N. M. C., Van Buggenhout, G., Hannes, F., Thienpont, B., Sanlaville, D., Kok, K., Midro, A., Andrieux, J., Anderlid, B.-M., Schoumans, J., Hordijk, R., Devriendt, K., Fryns, J.-P., Vermeesch, J. R.
<strong>Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH).</strong>
J. Med. Genet. 45: 71-80, 2008.
[PubMed: 17873117]
[Full Text: https://doi.org/10.1136/jmg.2007.052910]
</p>
</li>
<li>
<p class="mim-text-font">
McKeown, C., Read, A. P., Dodge, A., Stecko, O., Mercer, A., Harris, R.
<strong>Wolf-Hirschhorn locus is distal to D4S10 on short arm of chromosome 4.</strong>
J. Med. Genet. 24: 410-412, 1987.
[PubMed: 3612716]
[Full Text: https://doi.org/10.1136/jmg.24.7.410]
</p>
</li>
<li>
<p class="mim-text-font">
McQuibban, A. G., Joza, N., Megighian, A., Scorzeto, M., Zanini, D., Reipert, S., Richter, C., Schweyen, R. J., Nowikovsky, K.
<strong>A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome.</strong>
Hum. Molec. Genet. 19: 987-1000, 2010.
[PubMed: 20026556]
[Full Text: https://doi.org/10.1093/hmg/ddp563]
</p>
</li>
<li>
<p class="mim-text-font">
Naf, D., Wilson, L. A., Bergstrom, R. A., Smith, R. S., Goodwin, N. C., Verkerk, A., van Ommen, G. J., Ackerman, S. L., Frankel, W. L., Schimenti, J. C.
<strong>Mouse models for the Wolf-Hirschhorn deletion syndrome.</strong>
Hum. Molec. Genet. 10: 91-98, 2001.
[PubMed: 11152656]
[Full Text: https://doi.org/10.1093/hmg/10.2.91]
</p>
</li>
<li>
<p class="mim-text-font">
Nieminen, P., Kotilainen, J., Aalto, Y., Knuutila, S., Pirinen, S., Thesleff, I.
<strong>MSX1 gene is deleted in Wolf-Hirschhorn syndrome patients with oligodontia.</strong>
J. Dent. Res. 82: 1013-1017, 2003.
[PubMed: 14630905]
[Full Text: https://doi.org/10.1177/154405910308201215]
</p>
</li>
<li>
<p class="mim-text-font">
Nimura, K., Ura, K., Shiratori, H., Ikawa, M., Okabe, M., Schwartz, R. J., Kaneda, Y.
<strong>A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.</strong>
Nature 460: 287-291, 2009.
[PubMed: 19483677]
[Full Text: https://doi.org/10.1038/nature08086]
</p>
</li>
<li>
<p class="mim-text-font">
Oorthuys, J. W. E., Bleeker-Wagemakers, E. M.
<strong>A girl with the Pitt-Rogers-Danks syndrome.</strong>
Am. J. Med. Genet. 32: 140-141, 1989.
[PubMed: 2705474]
[Full Text: https://doi.org/10.1002/ajmg.1320320130]
</p>
</li>
<li>
<p class="mim-text-font">
Partington, M. W., Fagan, K., Soubjaki, V., Turner, G.
<strong>Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome.</strong>
J. Med. Genet. 34: 719-728, 1997.
[PubMed: 9321756]
[Full Text: https://doi.org/10.1136/jmg.34.9.719]
</p>
</li>
<li>
<p class="mim-text-font">
Pitt, D. B., Rogers, J. G., Danks, D. M.
<strong>Mental retardation, unusual face, and intrauterine growth retardation: a new recessive syndrome?</strong>
Am. J. Med. Genet. 19: 307-313, 1984.
[PubMed: 6542309]
[Full Text: https://doi.org/10.1002/ajmg.1320190213]
</p>
</li>
<li>
<p class="mim-text-font">
Quarrell, O. W. J., Snell, R. G., Curtis, M. A., Roberts, S. H., Harper, P. S., Shaw, D. J.
<strong>Paternal origin of the chromosomal deletion resulting in Wolf-Hirschhorn syndrome.</strong>
J. Med. Genet. 28: 256-259, 1991.
[PubMed: 1856831]
[Full Text: https://doi.org/10.1136/jmg.28.4.256]
</p>
</li>
<li>
<p class="mim-text-font">
Rodriguez, L., Zollino, M., Climent, S., Mansilla, E., Lopez-Grondona, F., Martinez-Fernandez, M. L., Murdolo, M., Martinez-Frias, M. L.
<strong>The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a second case.</strong>
Am. J. Med. Genet. 136A: 175-178, 2005.
[PubMed: 15948183]
[Full Text: https://doi.org/10.1002/ajmg.a.30775]
</p>
</li>
<li>
<p class="mim-text-font">
Shannon, N. L., Maltby, E. L., Rigby, A. S., Quarrell, O. W. J.
<strong>An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality.</strong>
J. Med. Genet. 38: 674-679, 2001.
[PubMed: 11584045]
[Full Text: https://doi.org/10.1136/jmg.38.10.674]
</p>
</li>
<li>
<p class="mim-text-font">
Tachdjian, G., Fondacci, C., Tapia, S., Huten, Y., Blot, P., Nessmann, C.
<strong>The Wolf-Hirschhorn syndrome in fetuses.</strong>
Clin. Genet. 42: 281-287, 1992.
[PubMed: 1493641]
[Full Text: https://doi.org/10.1111/j.1399-0004.1992.tb03257.x]
</p>
</li>
<li>
<p class="mim-text-font">
Thies, U., Back, E., Wolff, G., Schroeder-Kurth, T., Hager, H.-D., Schroder, K.
<strong>Clinical, cytogenetic and molecular investigations in three patients with Wolf-Hirschhorn syndrome.</strong>
Clin. Genet. 42: 201-205, 1992.
[PubMed: 1424245]
[Full Text: https://doi.org/10.1111/j.1399-0004.1992.tb03238.x]
</p>
</li>
<li>
<p class="mim-text-font">
Van Buggenhout, G., Melotte, C., Dutta, B., Froyen, G., Van Hummelen, P., Marynen, P., Matthijs, G., de Ravel, T., Devriendt, K., Fryns, J. P., Vermeesch, J. R.
<strong>Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map.</strong>
J. Med. Genet. 41: 691-698, 2004.
[PubMed: 15342700]
[Full Text: https://doi.org/10.1136/jmg.2003.016865]
</p>
</li>
<li>
<p class="mim-text-font">
Verbrugge, J., Choudhary, A. K., Ladda, R.
<strong>Tethered cord, corpus callosum abnormalities, and periventricular cysts in Wolf-Hirschhorn syndrome: Report of two cases and review of the literature.</strong>
Am. J. Med. Genet. 149A: 2280-2284, 2009.
[PubMed: 19764025]
[Full Text: https://doi.org/10.1002/ajmg.a.33022]
</p>
</li>
<li>
<p class="mim-text-font">
Wieczorek, D., Krause, M., Majewski, F., Albrecht, B., Meinecke, P., Riess, O., Gillessen-Kaesbach, G.
<strong>Unexpected high frequency of de novo unbalanced translocations in patients with Wolf-Hirschhorn syndrome (WHS). (Letter)</strong>
J. Med. Genet. 37: 798-804, 2000.
[PubMed: 11183188]
[Full Text: https://doi.org/10.1136/jmg.37.10.798]
</p>
</li>
<li>
<p class="mim-text-font">
Wieland, I., Muschke, P., Wieacker, P.
<strong>Further delineation of Wittwer syndrome and refinement of the mapping region.</strong>
Am. J. Med. Genet. 116A: 57-60, 2003.
[PubMed: 12476452]
[Full Text: https://doi.org/10.1002/ajmg.a.10874]
</p>
</li>
<li>
<p class="mim-text-font">
Wieland, I., Schanze, D., Schanze, I., Volleth, M., Muschke, P., Zenker, M.
<strong>A cryptic unbalanced translocation der(4)t(4;17)(p16.1;q25.3) identifies Wittwer syndrome as a variant of Wolf-Hirschhorn syndrome. (Letter)</strong>
Am. J. Med. Genet. 164A: 3213-3214, 2014.
[PubMed: 25251057]
[Full Text: https://doi.org/10.1002/ajmg.a.36765]
</p>
</li>
<li>
<p class="mim-text-font">
Wittwer, B., Kircheisen, R., Leutelt, J., Orth, U., Gal, A.
<strong>New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3.</strong>
Am. J. Med. Genet. 64: 42-49, 1996.
[PubMed: 8826447]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960712)64:1&lt;42::AID-AJMG6&gt;3.0.CO;2-T]
</p>
</li>
<li>
<p class="mim-text-font">
Wolf, U., Reinwein, H., Porsch, R., Schroter, R., Baitsch, H.
<strong>Defizienz an den kurzen Armen eines Chromosoms Nr. 4.</strong>
Humangenetik 1: 397-413, 1965.
[PubMed: 5868696]
</p>
</li>
<li>
<p class="mim-text-font">
Worthington, J. C., Rigby, A. S., Quarrell, O. W.
<strong>Seizure frequency in adults with Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 146A: 2528-2531, 2008.
[PubMed: 18792972]
[Full Text: https://doi.org/10.1002/ajmg.a.32483]
</p>
</li>
<li>
<p class="mim-text-font">
Wright, T. J., Altherr, M. R., Callen, D., Hirschhorn, K.
<strong>Reply to the letter to the editor by Partington and Turner--&#x27;Wolf-Hirschhorn and Pitt-Rogers-Danks syndrome&#x27;.</strong>
Am. J. Med. Genet. 82: 89-90, 1999.
</p>
</li>
<li>
<p class="mim-text-font">
Wright, T. J., Clemens, M., Quarrell, O., Altherr, M. R.
<strong>Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes caused by overlapping 4p deletions.</strong>
Am. J. Med. Genet. 75: 345-350, 1998.
[PubMed: 9482639]
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980203)75:4&lt;345::aid-ajmg2&gt;3.0.co;2-p]
</p>
</li>
<li>
<p class="mim-text-font">
Wright, T. J., Ricke, D. O., Denison, K., Abmayr, S., Cotter, P. D., Hirschhorn, K., Keinanen, M., McDonald-McGinn, D., Somer, M., Spinner, N., Yang-Feng, T., Zackai, E., Altherr, M. R.
<strong>A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region.</strong>
Hum. Molec. Genet. 6: 317-324, 1997.
[PubMed: 9063753]
[Full Text: https://doi.org/10.1093/hmg/6.2.317]
</p>
</li>
<li>
<p class="mim-text-font">
Zollino, M., Bova, R., Neri, G.
<strong>From Pitt-Rogers-Danks syndrome to Wolf-Hirschhorn syndrome and back?</strong>
Am. J. Med. Genet. 66: 113-115, 1996.
[PubMed: 8957527]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961202)66:1&lt;113::AID-AJMG29&gt;3.0.CO;2-U]
</p>
</li>
<li>
<p class="mim-text-font">
Zollino, M., Di Stefano, C., Zampino, G., Mastroiacovo, P., Wright, T. J., Sorge, G., Selicorni, A., Tenconi, R., Zappala, A., Battaglia, A., Di Rocco, M., Palka, G., Pallotta, R., Altherr, M. R., Neri, G.
<strong>Genotype-phenotype correlations and clinical diagnostic criteria in Wolf-Hirschhorn syndrome.</strong>
Am. J. Med. Genet. 94: 254-261, 2000.
[PubMed: 10995514]
[Full Text: https://doi.org/10.1002/1096-8628(20000918)94:3&lt;254::aid-ajmg13&gt;3.0.co;2-7]
</p>
</li>
<li>
<p class="mim-text-font">
Zollino, M., Lecce, R., Fischetto, R., Murdolo, M., Faravelli, F., Selicorni, A., Butte, C., Memo, L., Capovilla, G., Neri, G.
<strong>Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.</strong>
Am. J. Hum. Genet. 72: 590-597, 2003.
[PubMed: 12563561]
[Full Text: https://doi.org/10.1086/367925]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Carol A. Bocchini - updated : 3/10/2015<br>Cassandra L. Kniffin - updated : 6/5/2013<br>George E. Tiller - updated : 11/10/2011<br>Cassandra L. Kniffin - updated : 10/14/2010<br>Carol A. Bocchini - updated : 6/10/2010<br>Ada Hamosh - updated : 8/27/2009<br>Cassandra L. Kniffin - updated : 4/15/2009<br>Cassandra L. Kniffin - updated : 8/18/2008<br>Marla J. F. O&#x27;Neill - updated : 12/28/2005<br>Gregory S. Antonarakis - updated : 8/9/2005<br>Victor A. McKusick - updated : 11/15/2004<br>Victor A. McKusick - updated : 10/12/2004<br>Victor A. McKusick - updated : 2/26/2003<br>Victor A. McKusick - updated : 8/16/2002<br>Michael J. Wright - updated : 7/30/2002<br>George E. Tiller - updated : 3/12/2001<br>Victor A. McKusick - updated : 10/4/2000<br>Victor A. McKusick - updated : 5/5/1999<br>Victor A. McKusick - updated : 7/8/1998<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 4/21/1997
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 10/1/1987
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 07/17/2017<br>carol : 03/11/2015<br>mcolton : 3/11/2015<br>carol : 3/10/2015<br>alopez : 6/7/2013<br>ckniffin : 6/5/2013<br>alopez : 11/16/2011<br>alopez : 11/16/2011<br>terry : 11/10/2011<br>wwang : 10/19/2010<br>ckniffin : 10/14/2010<br>carol : 9/29/2010<br>terry : 8/9/2010<br>carol : 6/10/2010<br>carol : 6/10/2010<br>alopez : 9/30/2009<br>alopez : 9/8/2009<br>terry : 8/27/2009<br>wwang : 5/7/2009<br>ckniffin : 4/15/2009<br>carol : 2/26/2009<br>carol : 2/25/2009<br>wwang : 8/20/2008<br>ckniffin : 8/18/2008<br>wwang : 12/29/2005<br>terry : 12/28/2005<br>carol : 8/11/2005<br>terry : 8/9/2005<br>tkritzer : 11/18/2004<br>terry : 11/15/2004<br>tkritzer : 10/14/2004<br>terry : 10/12/2004<br>carol : 5/28/2003<br>alopez : 2/27/2003<br>terry : 2/26/2003<br>terry : 11/22/2002<br>tkritzer : 8/23/2002<br>tkritzer : 8/21/2002<br>terry : 8/16/2002<br>tkritzer : 8/6/2002<br>tkritzer : 8/2/2002<br>tkritzer : 8/1/2002<br>terry : 7/30/2002<br>mcapotos : 6/21/2001<br>cwells : 3/27/2001<br>cwells : 3/12/2001<br>cwells : 3/7/2001<br>mcapotos : 10/5/2000<br>mcapotos : 10/5/2000<br>terry : 10/4/2000<br>carol : 5/10/1999<br>terry : 5/5/1999<br>carol : 8/7/1998<br>terry : 7/8/1998<br>mark : 2/24/1998<br>terry : 2/19/1998<br>terry : 2/19/1998<br>jenny : 4/21/1997<br>mark : 10/6/1995<br>mimadm : 6/7/1995<br>carol : 5/14/1993<br>carol : 5/11/1993<br>carol : 4/5/1993<br>carol : 2/3/1993
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
</div>
</div>
</div>
<div class="visible-print-block mim-footer" style="position: relative;">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</sup> 1966-2025 Johns Hopkins University.
<br />
Printed: March 15, 2025
</div>
</div>
</div>
</div>
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
<div class="modal-dialog" role="document">
<div class="modal-content">
<div class="modal-header">
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">&times;</span></button>
<h4 class="modal-title" id="mimDonationPopupModalTitle">
OMIM Donation:
</h4>
</div>
<div class="modal-body">
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Dear OMIM User,
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
To ensure long-term funding for the OMIM project, we have diversified
our revenue stream. We are determined to keep this website freely
accessible. Unfortunately, it is not free to produce. Expert curators
review the literature and organize it to facilitate your work. Over 90%
of the OMIM's operating expenses go to salary support for MD and PhD
science writers and biocurators. Please join your colleagues by making a
donation now and again in the future. Donations are an important
component of our efforts to ensure long-term funding to provide you the
information that you need at your fingertips.
</p>
</div>
</div>
<div class="row">
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
<p>
Thank you in advance for your generous support, <br />
Ada Hamosh, MD, MPH <br />
Scientific Director, OMIM <br />
</p>
</div>
</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
Reference in a new issue View git blame Copy permalink