nih-gov/www.ncbi.nlm.nih.gov/books/NBK378974/index.html?report=reader

289 lines
135 KiB
Text

<!DOCTYPE html>
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
<head>
<!-- For pinger, set start time and add meta elements. -->
<script type="text/javascript">var ncbi_startTime = new Date();</script>
<!-- Logger begin -->
<meta name="ncbi_db" content="books">
<meta name="ncbi_pdid" content="book-part">
<meta name="ncbi_acc" content="NBK378974">
<meta name="ncbi_domain" content="gene">
<meta name="ncbi_report" content="reader">
<meta name="ncbi_type" content="fulltext">
<meta name="ncbi_objectid" content="">
<meta name="ncbi_pcid" content="/NBK378974/?report=reader">
<meta name="ncbi_pagename" content="Woodhouse-Sakati Syndrome - GeneReviews&reg; - NCBI Bookshelf">
<meta name="ncbi_bookparttype" content="chapter">
<meta name="ncbi_app" content="bookshelf">
<!-- Logger end -->
<!--component id="Page" label="meta"/-->
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Woodhouse-Sakati Syndrome - GeneReviews&reg; - NCBI Bookshelf</title>
<meta charset="utf-8">
<meta name="apple-mobile-web-app-capable" content="no">
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
<meta name="jr-col-layout" content="auto">
<meta name="jr-prev-unit" content="/books/n/gene/whs/?report=reader">
<meta name="jr-next-unit" content="/books/n/gene/x-ag/?report=reader">
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
<meta name="citation_inbook_title" content="GeneReviews&reg; [Internet]">
<meta name="citation_title" content="Woodhouse-Sakati Syndrome">
<meta name="citation_publisher" content="University of Washington, Seattle">
<meta name="citation_date" content="2021/07/08">
<meta name="citation_author" content="Saeed A Bohlega">
<meta name="citation_author" content="Ali Abusrair">
<meta name="citation_pmid" content="27489925">
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK378974/">
<meta name="citation_keywords" content="Hypogonadism, Alopecia, Diabetes Mellitus, Intellectual Disability, and Extrapyramidal Syndrome">
<meta name="citation_keywords" content="Hypogonadism, Alopecia, Diabetes Mellitus, Intellectual Disability, and Extrapyramidal Syndrome">
<meta name="citation_keywords" content="DDB1- and CUL4-associated factor 17">
<meta name="citation_keywords" content="DCAF17">
<meta name="citation_keywords" content="Woodhouse-Sakati Syndrome">
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
<meta name="DC.Title" content="Woodhouse-Sakati Syndrome">
<meta name="DC.Type" content="Text">
<meta name="DC.Publisher" content="University of Washington, Seattle">
<meta name="DC.Contributor" content="Saeed A Bohlega">
<meta name="DC.Contributor" content="Ali Abusrair">
<meta name="DC.Date" content="2021/07/08">
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK378974/">
<meta name="description" content="Virtually all individuals with Woodhouse-Sakati syndrome (WSS) have the endocrine findings of hypogonadism (evident at puberty) and progressive childhood-onset hair thinning that often progresses to alopecia totalis in adulthood. More than half of individuals have the neurologic findings of progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), moderate bilateral postlingual sensorineural hearing loss, and mild intellectual disability. To date, more than 40 families (including 33 with a molecularly confirmed diagnosis) with a total of 88 affected individuals have been reported in the literature.">
<meta name="og:title" content="Woodhouse-Sakati Syndrome">
<meta name="og:type" content="book">
<meta name="og:description" content="Virtually all individuals with Woodhouse-Sakati syndrome (WSS) have the endocrine findings of hypogonadism (evident at puberty) and progressive childhood-onset hair thinning that often progresses to alopecia totalis in adulthood. More than half of individuals have the neurologic findings of progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), moderate bilateral postlingual sensorineural hearing loss, and mild intellectual disability. To date, more than 40 families (including 33 with a molecularly confirmed diagnosis) with a total of 88 affected individuals have been reported in the literature.">
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK378974/">
<meta name="og:site_name" content="NCBI Bookshelf">
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png">
<meta name="twitter:card" content="summary">
<meta name="twitter:site" content="@ncbibooks">
<meta name="bk-non-canon-loc" content="/books/n/gene/wss/?report=reader">
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK378974/">
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&amp;subset=latin" rel="stylesheet" type="text/css">
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
<meta name="format-detection" content="telephone=no">
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
<meta name="ncbi_phid" content="CE8CAC9D7C8AC9E100000000011A00ED.m_5">
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
<body>
<!-- Book content! -->
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK378974/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
<style type="text/css">.st0{fill:#939598;}</style>
<g>
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
</g>
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/gene/whs/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">Woodhouse-Sakati Syndrome</div><div class="j">GeneReviews&#x000ae; [Internet]</div></div><div class="tail"><a href="/books/n/gene/x-ag/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK378974/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK378974/&amp;text=Woodhouse-Sakati%20Syndrome"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/gene/?report=reader">Title Information</a><a href="/books/n/gene/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK378974/?report=classic">Switch to classic view</a><a href="/books/NBK378974/pdf/Bookshelf_NBK378974.pdf">PDF (1.2M)</a><a href="/books/NBK378974/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK378974%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8CAC9D7C8AC9E100000000011A00ED.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">&#10008;</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">&#10008;</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">&#9664;</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">&#9654;</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK378974_"><span class="title" itemprop="name">Woodhouse-Sakati Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Hypogonadism, Alopecia, Diabetes Mellitus, Intellectual Disability, and Extrapyramidal Syndrome</div><p class="contribs">Bohlega SA, Abusrair A.</p><p class="fm-aai"><a href="#_NBK378974_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 20 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="wss.Summary" itemprop="description"><h2 id="_wss_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Virtually all individuals with Woodhouse-Sakati syndrome (WSS) have the endocrine findings of hypogonadism (evident at puberty) and progressive childhood-onset hair thinning that often progresses to alopecia totalis in adulthood. More than half of individuals have the neurologic findings of progressive extrapyramidal movements (dystonic spasms with dystonic posturing with dysarthria and dysphagia), moderate bilateral postlingual sensorineural hearing loss, and mild intellectual disability. To date, more than 40 families (including 33 with a molecularly confirmed diagnosis) with a total of 88 affected individuals have been reported in the literature.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of WSS is established in a proband with suggestive clinical, neuroimaging, and neurophysiologic findings by identification of biallelic pathogenic variants in <i>DCAF17</i> on molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment is symptomatic and should be managed by a multidisciplinary team. Hypogonadism requires hormone replacement therapy to induce secondary sex characteristics and promote bone health at the usual age of puberty. Alopecia is treated symptomatically for cosmetic reasons only. Treatment for dystonia is routine; oral medications are tried first and followed in some instances by botulinum toxin injection and/or deep-brain stimulation. Dysarthria often benefits from consultation with a speech therapist. Those with dysphagia often require measures to reduce oral secretions, use of thickened liquids and pureed foods to avoid aspiration, and eventually a gastrostomy to help maintain caloric intake. Standard treatment for diabetes mellitus, hypothyroidism, hearing loss, and intellectual disability.</p><p><i>Surveillance:</i> Monitoring for endocrine abnormalities is recommended at the following ages: hypogonadism beginning at age 12-14 years; diabetes mellitus and hypothyroidism beginning at age 20 years; serum IGF-1 every three to five years following diagnosis; annual neurologic assessment for dystonia; speech and language assessment for dysarthria and dysphagia as needed; annual developmental assessment throughout childhood; annual audiology evaluation.</p><p><i>Agents/circumstances to avoid:</i> Persons with dystonia should avoid situations in which the risk of falling is increased.</p><p><i>Evaluation of relatives at risk:</i> Molecular genetic testing for the <i>DCAF17</i> pathogenic variants identified in the proband is appropriate for evaluation of apparently asymptomatic older and younger sibs to identify as early as possible those who would benefit from early identification and treatment of potential complications.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>WSS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic <i>DCAF17</i> variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.</p></div></div><div id="wss.Diagnosis"><h2 id="_wss_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for Woodhouse-Sakati syndrome (WSS) have been published.</p><div id="wss.Suggestive_Findings"><h3>Suggestive Findings</h3><p>WSS <b>should be suspected</b> in individuals with any combination of the following clinical, family history, neuroimaging, and neurophysiology findings.</p><p>
<b>Endocrine</b>
</p><ul><li class="half_rhythm"><div>Hypogonadism (100% of individuals), hypogonadotropic in males and hypergonadotropic in females</div><ul><li class="half_rhythm"><div>Primary amenorrhea in females</div></li><li class="half_rhythm"><div>Lack of development of secondary sexual characteristics in males and females</div></li></ul></li><li class="half_rhythm"><div>Low insulin-like growth factor 1 (IGF-1) (100%)</div></li><li class="half_rhythm"><div>Adolescent- to young adult-onset diabetes mellitus (66%)</div></li><li class="half_rhythm"><div>Hypothyroidism (30%)</div></li></ul><p><b>Alopecia.</b> Hair loss beginning in childhood or adolescence, resulting in partial-to-complete loss of scalp hair and eyelashes (100%) (<a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">Figure 1A</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">1H</a>)</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figwssF1" co-legend-rid="figlgndwssF1"><a href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figwssF1" rid-ob="figobwssF1"><img class="small-thumb" src="/books/NBK378974/bin/wss-Image001.gif" src-large="/books/NBK378974/bin/wss-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndwssF1"><h4 id="wss.F1"><a href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-ob="figobwssF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Affected individuals from different families with WSS who have variable degrees of alopecia or hair loss and neurologic involvement A. Male age 23 with flat occiput; temporal and frontal alopecia</p></div></div><p>
<b>Neurologic</b>
</p><ul><li class="half_rhythm"><div>Adolescent to young-adult onset of extrapyramidal findings including focal (later generalized) dystonia (65%), chorea, dysarthria, and dysphagia</div></li><li class="half_rhythm"><div>Sensorineural hearing loss (SNHL) with onset in childhood (62%)</div></li><li class="half_rhythm"><div>Intellectual disability (58%)</div></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p><div id="wss.Supportive_Findings"><h4>Supportive Findings</h4><p>
<b>Neuroimaging findings on brain MRI</b>
</p><ul><li class="half_rhythm"><div>Partially empty sella and a small pituitary gland (<a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">Figure 2A</a>) [<a class="bibr" href="#wss.REF.abusrair.2018.2256" rid="wss.REF.abusrair.2018.2256">Abusrair et al 2018</a>]</div></li><li class="half_rhythm"><div>Progressive frontoparietal/periventricular white matter lesions (<a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">Figure 2B</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">2C</a>) [<a class="bibr" href="#wss.REF.abusrair.2018.2256" rid="wss.REF.abusrair.2018.2256">Abusrair et al 2018</a>, <a class="bibr" href="#wss.REF.leh_ricy.2020.462" rid="wss.REF.leh_ricy.2020.462">Leh&#x000e9;ricy et al 2020</a>]</div></li><li class="half_rhythm"><div>Iron deposition in the globus pallidus (<a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">Figure 2D</a>), and to a lesser extent, in the substantia nigra and red nucleus [<a class="bibr" href="#wss.REF.abusrair.2018.2256" rid="wss.REF.abusrair.2018.2256">Abusrair et al 2018</a>, <a class="bibr" href="#wss.REF.lee.2020.1024" rid="wss.REF.lee.2020.1024">Lee et al 2020</a>]</div></li><li class="half_rhythm"><div>Rarely, prominent perivascular spaces and diffusion restriction involving the splenium of the corpus callosum (<a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">Figure 2E</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-figpopup="figwssF2" rid-ob="figobwssF2">2F</a>) [<a class="bibr" href="#wss.REF.abusrair.2018.2256" rid="wss.REF.abusrair.2018.2256">Abusrair et al 2018</a>]</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figwssF2" co-legend-rid="figlgndwssF2"><a href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figwssF2" rid-ob="figobwssF2"><img class="small-thumb" src="/books/NBK378974/bin/wss-Image002.gif" src-large="/books/NBK378974/bin/wss-Image002.jpg" alt="Figure 2. . Brain MRI of individuals with WSS." /></a><div class="icnblk_cntnt" id="figlgndwssF2"><h4 id="wss.F2"><a href="/books/NBK378974/figure/wss.F2/?report=objectonly" target="object" rid-ob="figobwssF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Brain MRI of individuals with WSS. Arrows indicate the following findings: A. Sagittal T<sub>1</sub>-weighted image, showing small pituitary gland and partially empty sella.</p></div></div><p><b>Neurophysiology findings on evoked-potential (EP) analysis</b> [<a class="bibr" href="#wss.REF.abusrair.2020" rid="wss.REF.abusrair.2020">Abusrair et al 2020</a>]</p><ul><li class="half_rhythm"><div>Prolonged P100 latencies on pattern reversal visual EPs</div></li><li class="half_rhythm"><div>Prolonged cortical N19 response on median somatosensory EPs</div></li><li class="half_rhythm"><div>Absent or prolonged P37 cortical response on tibial somatosensory EPs</div></li></ul></div></div><div id="wss.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of WSS <b>is established</b> in a proband with suggestive clinical, neuroimaging, and neurophysiologic findings by identification of biallelic pathogenic variants in <i>DCAF17</i> on molecular genetic testing (see <a href="/books/NBK378974/table/wss.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobwssTmoleculargenetictestingusedin">Table 1</a>).</p><p>Molecular testing approaches can include <b>gene-targeted testing</b> (single-gene testing or multigene panel) and <b>comprehensive</b>
<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#wss.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#wss.Option_1">Option 1</a>), whereas those in whom the diagnosis of WSS has not been considered are more likely to be diagnosed using genomic testing (see <a href="#wss.Option_2">Option 2</a>).</p><div id="wss.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>DCAF17</i> identifies biallelic pathogenic variants in all individuals with typical findings of WSS. <i>DCAF17</i> exon and whole-gene deletion/duplication variants have not been reported. However, gene-targeted deletion/duplication analysis may be useful to confirm homozygosity of a pathogenic variant detected by sequence analysis when parental DNA is not available (see <a href="#wss.Molecular_Genetics">Molecular Genetics</a>).</p><p>Note: Targeted analysis for individuals who are Saudi Arabian or Qatari may be performed first. To date, all affected individuals in these populations have been homozygous for the same founder pathogenic variant, <a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobwssTnotabledcaf17pathogenicvariants">c.436delC</a> [<a class="bibr" href="#wss.REF.alazami.2008.684" rid="wss.REF.alazami.2008.684">Alazami et al 2008</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>].</p><p><b>A multigene panel</b> that includes <i>DCAF17</i> and other genes of interest (see <a href="#wss.Differential_Diagnosis">Differential Diagnosis</a>) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="wss.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
<b>genomic testing</b> does not require the clinician to determine which gene is likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTmoleculargenetictestingusedin"><a href="/books/NBK378974/table/wss.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobwssTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.molecular_genetic_testing_used_in"><a href="/books/NBK378974/table/wss.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobwssTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Woodhouse-Sakati Syndrome </p></div></div></div></div></div><div id="wss.Clinical_Characteristics"><h2 id="_wss_Clinical_Characteristics_">Clinical Characteristics</h2><div id="wss.Clinical_Description"><h3>Clinical Description</h3><p>Woodhouse-Sakati syndrome (WSS) is characterized by the endocrine findings of hypogonadism, diabetes mellitus, and hypothyroidism and progressive childhood-onset alopecia along with neurologic findings of progressive extrapyramidal movements, sensorineural hearing loss, and intellectual disability. To date, 88 individuals from more than 40 families have been reported [<a class="bibr" href="#wss.REF.steindl.2010.594" rid="wss.REF.steindl.2010.594">Steindl et al 2010</a>, <a class="bibr" href="#wss.REF.nanda.2014.83" rid="wss.REF.nanda.2014.83">Nanda et al 2014</a>, <a class="bibr" href="#wss.REF.abdulla.2015.489" rid="wss.REF.abdulla.2015.489">Abdulla et al 2015</a>, <a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>].</p><p>Two clinical types of WSS have been described [<a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>] with variable prognosis. However, intrafamilial variability is common and both types can occur within a family:</p><ul><li class="half_rhythm"><div><b>Type 1.</b> Severe and progressive neurologic disability at a younger age (range 9-17 years) causing significant impairment of the quality of life and activities of daily living. Manifestations include severe intellectual disability and dystonia.</div></li><li class="half_rhythm"><div><b>Type 2.</b> Absent or mild neurologic involvements that do not affect activities of daily living</div></li></ul><div id="wss.Endocrine"><h4>Endocrine</h4><p><b>Hypogonadism,</b> present in all affected individuals, manifests as delayed puberty with lack of secondary sexual characteristics. The nature of hypogonadism has been difficult to characterize as both hypergonadotropic and hypogonadotropic hypogonadism have been described [<a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>]; in about 30% of affected individuals the hormonal profile does not neatly fit either group. Sense of smell is normal.</p><p>Women typically have primary amenorrhea. Detailed endocrine investigation in more than 50 of the women described in the literature typically revealed severely reduced or absent estradiol and high FSH and LH, consistent with hypergonadotropic hypogonadism. There appears to be decreased hypothalamic-pituitary responsiveness, as the FSH and LH are not as high as expected for the degree of ovarian failure [<a class="bibr" href="#wss.REF.woodhouse.1983.216" rid="wss.REF.woodhouse.1983.216">Woodhouse &#x00026; Sakati 1983</a>, <a class="bibr" href="#wss.REF.rachmiel.2011.362" rid="wss.REF.rachmiel.2011.362">Rachmiel et al 2011</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p>The ovaries are streak or underdeveloped, and not visualized by laparotomy, laparoscopy, or autopsy [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>, <a class="bibr" href="#wss.REF.rachmiel.2011.362" rid="wss.REF.rachmiel.2011.362">Rachmiel et al 2011</a>]. Ovarian biopsy showed fibrous tissue with no identifiable oocysts [<a class="bibr" href="#wss.REF.woodhouse.1983.216" rid="wss.REF.woodhouse.1983.216">Woodhouse &#x00026; Sakati 1983</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p>Men have moderately low testosterone and &#x02013; in contrast to women &#x02013; inappropriately low gonadotropins, consistent with hypogonadotropic hypogonadism, which may be of central or central and peripheral etiology. Semen analysis may show azoospermia [<a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>, <a class="bibr" href="#wss.REF.ali.2016.263" rid="wss.REF.ali.2016.263">Ali et al 2016</a>]. One male had cryptorchidism [<a class="bibr" href="#wss.REF.rachmiel.2011.362" rid="wss.REF.rachmiel.2011.362">Rachmiel et al 2011</a>].</p><p>Although the testes are of normal size, testicular biopsy reveals reduced spermatogenesis with predominance of Sertoli cells and few Leydig cells [<a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p><b>Low insulin-like growth factor 1 (IGF-1)</b> is present in all individuals [<a class="bibr" href="#wss.REF.ali.2016.263" rid="wss.REF.ali.2016.263">Ali et al 2016</a>]. Reduction of IGF-1 is more pronounced in females [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>]. The low IGF-1 levels may reflect low sex steroids resulting from hypogonadism.</p><p>The growth pattern is normal and growth hormone levels are usually normal; short stature is not a part of this syndrome [<a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p><b>Diabetes mellitus.</b> Type 2 diabetes (either insulin dependent or non-insulin dependent) was reported in 66% of all individuals and 96% of those older than age 25 years [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p><b>Hypothyroidism</b> of peripheral origin (primary but without evidence of autoimmunity) was found in 30% of individuals, typically around age 20 years [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>].</p><p><b>Other.</b> No abnormalities of the corticotropic axis or prolactin [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>] have been reported.</p></div><div id="wss.Ectodermal"><h4>Ectodermal</h4><p><b>Alopecia.</b> All affected individuals have predominantly frontotemporal alopecia with sparse, thin scalp hair. Hair loss begins in childhood and often progresses to alopecia totalis in the third or fourth decade or earlier. Eyelashes and eyebrows are absent or sparse. In men, facial hair is absent or underdeveloped.</p><p>Scanning electron microscopy of the hair shows longitudinal grooves with no specific abnormalities [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>].</p><p><b>Facial skin</b> is often wrinkled in advanced stages, conferring a progeroid appearance [<a class="bibr" href="#wss.REF.woodhouse.1983.216" rid="wss.REF.woodhouse.1983.216">Woodhouse &#x00026; Sakati 1983</a>, <a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p><b>Anodontia.</b> Total loss of teeth is rare; when it occurs, it is usually seen at a later stage [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</p><p><b>Nails</b> appear to be normal.</p></div><div id="wss.Neurologic"><h4>Neurologic</h4><p><b>Extrapyramidal abnormal movement</b> was seen in more than 56% of reported individuals. In particular, dystonic spasms with dystonic posturing were seen in the majority, including segmental dystonia affecting the craniocervical region, oromandibular region, or one extremity. Often, the first neurologic manifestation is abnormal posturing movements that typically start insidiously in childhood or the early teens. Dysarthria (often with a high-pitched voice) and dysphagia are common.</p><p>In a majority of individuals, dystonia becomes generalized and disabling (<a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">Figure 1B</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">1F</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">1H</a>). Progressive dystonia of the trunk may lead to severe dystonic scoliosis. As the dystonia progresses, gait difficulties ultimately lead to immobility.</p><p>Inter- and intrafamilial variability is common [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>, <a class="bibr" href="#wss.REF.ali.2016.263" rid="wss.REF.ali.2016.263">Ali et al 2016</a> , <a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>]. For example, families with the founder <i>DCAF17</i> pathogenic variant (<a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobwssTnotabledcaf17pathogenicvariants">c.436delC</a>) can have dystonia [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>] or not [<a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>]. Of note, although extrapyramidal features were not mentioned in the original report of <a class="bibr" href="#wss.REF.woodhouse.1983.216" rid="wss.REF.woodhouse.1983.216">Woodhouse and Sakati [1983]</a>, it was found that up to 65% of affected individuals develop variable degrees of dystonia at some point in the disease course (<a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">Figure 1H</a>) [<a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a> ].</p><p><b>Sensorineural hearing loss (SNHL).</b> Moderate bilateral SNHL was noted in 62% of reports. When present, deafness is invariably postlingual, usually starting in adolescence [<a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>].</p><p><b>Intellectual disability</b> is described in 58% of individuals. It is typically mild and usually overshadowed by accompanying severe and disabling dystonia, dysarthria, and SNHL. The authors have observed ten individuals who were able to complete a college education and hold permanent manual occupations [Author, personal observation].</p><p><b>Other.</b> Seizures with onset in early childhood, tremors, and mild Parkinsonism features have rarely been reported [<a class="bibr" href="#wss.REF.alsemari.2007.149" rid="wss.REF.alsemari.2007.149">Al-Semari &#x00026; Bohlega 2007</a>, <a class="bibr" href="#wss.REF.schneider.2008.592" rid="wss.REF.schneider.2008.592">Schneider &#x00026; Bhatia 2008</a>, <a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>].</p><p>Polyneuropathy with stocking glove sensory loss and diminished deep tendon reflexes but normal strength has been reported [<a class="bibr" href="#wss.REF.schneider.2008.592" rid="wss.REF.schneider.2008.592">Schneider &#x00026; Bhatia 2008</a>].</p></div><div id="wss.Other_Findings"><h4>Other Findings</h4><p><b>Dysmorphic facial features</b> include a long triangular face, prominent nasal bridge, widely spaced eyes, and sparse eyebrows, creating a characteristic facial appearance (<a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">Figure 1D</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">1E</a>, <a class="figpopup" href="/books/NBK378974/figure/wss.F1/?report=objectonly" target="object" rid-figpopup="figwssF1" rid-ob="figobwssF1">1G</a>).</p><p><b>Bilateral keratoconus</b> was reported in four individuals [<a class="bibr" href="#wss.REF.alswailem.2006.116" rid="wss.REF.alswailem.2006.116">Al-Swailem et al 2006</a>, <a class="bibr" href="#wss.REF.schneider.2008.592" rid="wss.REF.schneider.2008.592">Schneider &#x00026; Bhatia 2008</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>].</p><p><b>Electrocardiographic (EKG) abnormalities</b> (lengthening of the ST segments and T-wave flattening) were described in the original report [<a class="bibr" href="#wss.REF.woodhouse.1983.216" rid="wss.REF.woodhouse.1983.216">Woodhouse &#x00026; Sakati 1983</a>] but rarely reported subsequently [<a class="bibr" href="#wss.REF.koshy.2008.57" rid="wss.REF.koshy.2008.57">Koshy et al 2008</a>, <a class="bibr" href="#wss.REF.schneider.2008.592" rid="wss.REF.schneider.2008.592">Schneider &#x00026; Bhatia 2008</a>]. Of note, these EKG abnormalities were asymptomatic and individuals with WSS have no major cardiac manifestations.</p></div></div><div id="wss.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>There is no clear genotype-phenotype correlation. Even individuals with the same Saudi Arabian founder <i>DCAF17</i> pathogenic variant (<a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobwssTnotabledcaf17pathogenicvariants">c.436delC</a>) have displayed marked phenotypic variability.</p></div><div id="wss.Prevalence"><h3>Prevalence</h3><p>To date, more than 40 families with an estimated 88 affected individuals have been reported. Of these, 51 individuals from 33 families have had the diagnosis confirmed molecularly.</p><p>The carrier frequency of the Saudi Arabian founder variant (<a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobwssTnotabledcaf17pathogenicvariants">c.436delC</a>) is 0.00243309 [<a class="bibr" href="#wss.REF.abouelhoda.2016.1244" rid="wss.REF.abouelhoda.2016.1244">Abouelhoda et al 2016</a>].</p></div></div><div id="wss.Genetically_Related_Allelic_Disorder"><h2 id="_wss_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>DCAF17</i>.</p></div><div id="wss.Differential_Diagnosis"><h2 id="_wss_Differential_Diagnosis_">Differential Diagnosis</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTdisordersphenotypestoconsiderin"><a href="/books/NBK378974/table/wss.T.disordersphenotypes_to_consider_in/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobwssTdisordersphenotypestoconsiderin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.disordersphenotypes_to_consider_in"><a href="/books/NBK378974/table/wss.T.disordersphenotypes_to_consider_in/?report=objectonly" target="object" rid-ob="figobwssTdisordersphenotypestoconsiderin">Table 2. </a></h4><p class="float-caption no_bottom_margin">Disorders/Phenotypes to Consider in the Differential Diagnosis of Woodhouse-Sakati Syndrome </p></div></div><p>Other disorders to consider in the differential diagnosis of Woodhouse-Sakati syndrome (WSS):</p><ul><li class="half_rhythm"><div><b>Hereditary dystonia.</b> Hereditary dystonia is associated with extensive clinical and genetic heterogeneity (see <a href="/books/n/gene/dystonia-ov/?report=reader">Hereditary Dystonia Overview</a>). Unlike WSS, hypogonadism and alopecia are not known to be features associated with hereditary dystonia.</div></li><li class="half_rhythm"><div><b>Hereditary hearing loss and deafness.</b> Nonsyndromic hereditary hearing loss is characterized by extreme genetic heterogeneity: to date, more than 6,000 causative variants have been identified in more than 110 genes. Syndromic hearing impairment is known to be associated with more than 400 genetic syndromes. (See <a href="/books/n/gene/deafness-overview/?report=reader">Hereditary Hearing Loss and Deafness Overview</a>.)</div></li></ul></div><div id="wss.Management"><h2 id="_wss_Management_">Management</h2><div id="wss.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with Woodhouse-Sakati syndrome (WSS), the evaluations summarized in <a href="/books/NBK378974/table/wss.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobwssTrecommendedevaluationsfollowing">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTrecommendedevaluationsfollowing"><a href="/books/NBK378974/table/wss.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobwssTrecommendedevaluationsfollowing"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.recommended_evaluations_following"><a href="/books/NBK378974/table/wss.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobwssTrecommendedevaluationsfollowing">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Woodhouse-Sakati Syndrome </p></div></div></div><div id="wss.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>No specific treatment exists for WSS. Treatment is aimed at relieving symptoms [<a class="bibr" href="#wss.REF.albanese.2015.1547" rid="wss.REF.albanese.2015.1547">Albanese et al 2015</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTtreatmentofmanifestationsinind"><a href="/books/NBK378974/table/wss.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobwssTtreatmentofmanifestationsinind"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.treatment_of_manifestations_in_ind"><a href="/books/NBK378974/table/wss.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object" rid-ob="figobwssTtreatmentofmanifestationsinind">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Woodhouse-Sakati Syndrome </p></div></div></div><div id="wss.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTrecommendedsurveillanceforindiv"><a href="/books/NBK378974/table/wss.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobwssTrecommendedsurveillanceforindiv"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.recommended_surveillance_for_indiv"><a href="/books/NBK378974/table/wss.T.recommended_surveillance_for_indiv/?report=objectonly" target="object" rid-ob="figobwssTrecommendedsurveillanceforindiv">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Woodhouse-Sakati Syndrome </p></div></div></div><div id="wss.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Persons with dystonia should avoid situations in which the risk of falling is increased.</p></div><div id="wss.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>Molecular genetic testing for known familial <i>DCAF17</i> pathogenic variants is appropriate for the evaluation of apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who will benefit from early identification and treatment of potential complications.</p><p>See <a href="#wss.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="wss.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="wss.Genetic_Counseling"><h2 id="_wss_Genetic_Counseling_">Genetic Counseling</h2><p>
<i>Genetic counseling is the process of providing individuals and families with
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
make informed medical and personal decisions. The following section deals with genetic
risk assessment and the use of family history and genetic testing to clarify genetic
status for family members; it is not meant to address all personal, cultural, or
ethical issues that may arise or to substitute for consultation with a genetics
professional</i>. &#x02014;ED.</p><div id="wss.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Woodhouse-Sakati syndrome (WSS) is inherited in an autosomal recessive manner.</p></div><div id="wss.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
<b>Parents of a proband</b>
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one <i>DCAF17</i> pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a <i>DCAF17</i> pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#wss.REF.j_nsson.2017.519" rid="wss.REF.j_nsson.2017.519">J&#x000f3;nsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
<b>Sibs of a proband</b>
</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a <i>DCAF17</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic <i>DCAF17</i> pathogenic variants and being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>The neurologic phenotype in a sib who inherits biallelic pathogenic variants cannot be predicted based on the phenotype in the proband; an affected sib may have a neurologic phenotype ranging from normal to severe regardless of the neurologic features observed in the proband [<a class="bibr" href="#wss.REF.bohlega.2019.99" rid="wss.REF.bohlega.2019.99">Bohlega et al 2019</a>].</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p><b>Offspring of a proband.</b> Unless an individual with WSS has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>DCAF17</i>.</p><p><b>Other family members.</b> Each sib of the proband&#x02019;s parents is at a 50% risk of being a carrier of a <i>DCAF17</i> pathogenic variant.</p></div><div id="wss.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>DCAF17</i> pathogenic variants in the family.</p></div><div id="wss.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#wss.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
<b>Family planning</b>
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul></div><div id="wss.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>DCAF17</i> pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for WSS are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="wss.Resources"><h2 id="_wss_Resources_">Resources</h2><p>
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
support organizations and/or registries for the benefit of individuals with this disorder
and their families. GeneReviews is not responsible for the information provided by other
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
<ul><li class="half_rhythm"><div>
<b>NBIA Disorders Association</b>
</div><div>
<a href="https://www.nbiadisorders.org/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">www.nbiadisorders.org</a>
</div></li><li class="half_rhythm"><div>
<b>Dystonia Medical Research Foundation</b>
</div><div><b>Phone:</b> 312-755-0198; 800-377-DYST (3978)</div><div><b>Email:</b> dystonia@dystonia-foundation.org</div><div>
<a href="http://www.dystonia-foundation.org" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">dystonia-foundation.org</a>
</div></li><li class="half_rhythm"><div>
<b>Dystonia UK</b>
</div><div>United Kingdom</div><div><b>Email:</b> info@dystonia.org.uk</div><div>
<a href="http://www.dystonia.org.uk" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">dystonia.org.uk</a>
</div></li><li class="half_rhythm"><div>
<b>NBIAcure</b>
</div><div>Center of Excellence for NBIA Clinical Care and Research</div><div>International Registry for NBIA and Related Disorders</div><div>Oregon Health &#x00026; Science University</div><div><b>Email:</b> info@nbiacure.org</div><div>
<a href="http://nbiacure.org" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">www.nbiacure.org</a>
</div></li><li class="half_rhythm"><div>
<b>Treat Iron-Related Childhood Onset Neurodegeneration (TIRCON)</b>
</div><div>Germany</div><div><b>Email:</b> TIRCON@med.uni-muenchen.de</div><div>
<a href="https://tircon.eu/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">www.TIRCON.eu</a>
</div></li></ul>
</div><div id="wss.Molecular_Genetics"><h2 id="_wss_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. &#x02014;</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssmolgenTA"><a href="/books/NBK378974/table/wss.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobwssmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.molgen.TA"><a href="/books/NBK378974/table/wss.molgen.TA/?report=objectonly" target="object" rid-ob="figobwssmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Woodhouse-Sakati Syndrome: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssmolgenTB"><a href="/books/NBK378974/table/wss.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobwssmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.molgen.TB"><a href="/books/NBK378974/table/wss.molgen.TB/?report=objectonly" target="object" rid-ob="figobwssmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Woodhouse-Sakati Syndrome (View All in OMIM) </p></div></div><div id="wss.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>Alternate splicing of <i>DCAF17</i> results in multiple transcripts of variable length. The longest transcript, NM_025000.4, has 14 exons. In comparison another major transcript, NM_001164821.1, lacks two exons in the coding region for a total of 12 exons. Transcript <a href="/nuccore/NM_025000.3" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NM_025000.4</a> encodes DDB1- and CUL4-associated factor 17, a 520 amino-acid protein known as the &#x003b1; isoform (<a href="/protein/NP_079276.2" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NP_079276.2</a>). This is a nucleolar protein of unknown function expressed in various tissues including brain, skin, and liver &#x02013; which correlates to some extent with the multiorgan involvement in individuals with Woodhouse-Sakati syndrome (WSS).</p><p>Reported <i>DCAF17</i> pathogenic variants include small intragenic deletions, nonsense and splice site variants, and small indels [<a class="bibr" href="#wss.REF.alazami.2010.585" rid="wss.REF.alazami.2010.585">Alazami et al 2010</a>, <a class="bibr" href="#wss.REF.habib.2011.26" rid="wss.REF.habib.2011.26">Habib et al 2011</a>, <a class="bibr" href="#wss.REF.abdulla.2015.489" rid="wss.REF.abdulla.2015.489">Abdulla et al 2015</a>, <a class="bibr" href="#wss.REF.ali.2016.263" rid="wss.REF.ali.2016.263">Ali et al 2016</a>]. Pathogenic <i>DCAF17</i> missense variants have not been described.</p><p>Of the 33 families with molecularly confirmed WSS, biallelic compound heterozygous <i>DCAF17</i> pathogenic variants has been reported in only one [<a class="bibr" href="#wss.REF.ali.2016.263" rid="wss.REF.ali.2016.263">Ali et al 2016</a>]. The remaining families were homozygous for <i>DCAF17</i> pathogenic variants. Gene-targeted deletion/duplication analysis may be useful to confirm apparent homozygosity of a pathogenic variant detected by sequence analysis when parental DNA samples are not available.</p><p><b>Mechanism of disease causation.</b> The types of pathogenic variants known to result in WSS predict premature translation termination, missplicing, or nonsense-mediated decay, suggesting that WSS results from loss of DCAF17 function.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figwssTnotabledcaf17pathogenicvariants"><a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobwssTnotabledcaf17pathogenicvariants"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="wss.T.notable_dcaf17_pathogenic_variants"><a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobwssTnotabledcaf17pathogenicvariants">Table 6. </a></h4><p class="float-caption no_bottom_margin">Notable <i>DCAF17</i> Pathogenic Variants </p></div></div></div></div><div id="wss.Chapter_Notes"><h2 id="_wss_Chapter_Notes_">Chapter Notes</h2><div id="wss.Author_History"><h3>Author History</h3><p>Ali Abusrair, MD (2021-present)<br />Fowzan S Alkuraya, MD (Hons), ABP, ABMGG; King Faisal Specialist Hospital and Research Center (2016-2021)<br />Saeed A Bohlega, MD, FRCPC, FAAN (2016-present)</p></div><div id="wss.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>8 July 2021 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>4 August 2016 (bp) Review posted live</div></li><li class="half_rhythm"><div>2 February 2016 (sab) Original submission</div></li></ul></div></div><div id="wss.References"><h2 id="_wss_References_">References</h2><div id="wss.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.abdulla.2015.489">Abdulla MC, Alazami AM, Alungal J, Koya JM, Musambil M. Novel compound heterozygous frameshift mutations of C2orf37 in a familial Indian case of Woodhouse-Sakati syndrome. <span><span class="ref-journal">J Genet. </span>2015;<span class="ref-vol">94</span>:489&ndash;92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26440089" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 26440089</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.abouelhoda.2016.1244">Abouelhoda M, Sobahy T, El-Kalioby M, Patel N, Shamseldin H, Monies D, Al-Tassan N, Ramzan K, Imtiaz F, Shaheen R, Alkuraya FS. Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden. <span><span class="ref-journal">Genet Med. </span>2016;<span class="ref-vol">18</span>:1244&ndash;9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27124789" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 27124789</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.abusrair.2020">Abusrair A, AlHamoud I, Bohlega S. Multimodal evoked potential profiles in Woodhouse-Sakati syndrome. <span><span class="ref-journal">J Clin Neurophysiol. </span>2020.</span> Epub ahead of print. [<a href="https://pubmed.ncbi.nlm.nih.gov/33417382" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 33417382</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.abusrair.2018.2256">Abusrair AH, Bohlega S, Al-Semari A, Al-Ajlan FS, Al-Ahmadi K, Mohamed B, AlDakheel A. Brain MR imaging findings in Woodhouse-Sakati syndrome. <span><span class="ref-journal">AJNR Am J Neuroradiol. </span>2018;<span class="ref-vol">39</span>:2256&ndash;62.</span> [<a href="/pmc/articles/PMC7655421/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC7655421</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30409855" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 30409855</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.agopiantz.2014.1">Agopiantz M, Corbonnois P, Sorlin A, Bonnet C, Klein M, Hubert N, Pascal-Vigneron V, Jonveaux P, Cuny T, Leheup B, Weryha G. Endocrine disorders in Woodhouse-Sakati syndrome: a systematic review of the literature. <span><span class="ref-journal">J Endocrinol Invest. </span>2014;<span class="ref-vol">37</span>:1&ndash;7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24464444" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 24464444</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.alazami.2008.684">Alazami AM, Al-Saif A, Al-Semari A, Bohlega S, Zlitni S, Alzahrani F, Bavi P, Kaya N, Colak D, Khalak H, Baltus A, Peterlin B, Danda S, Bhatia KP, Schneider SA, Sakati N, Walsh CA, Al-Mohanna F, Meyer B, Alkuraya FS. Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2008;<span class="ref-vol">83</span>:684&ndash;91.</span> [<a href="/pmc/articles/PMC2668059/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC2668059</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19026396" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 19026396</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.alazami.2010.585">Alazami AM, Schneider SA, Bonneau D, Pasquier L, Carecchio M, Kojovic M, Steindl K, de Kerdanet M, Nezarati MM, Bhatia KP, Degos B, Goh E, Alkuraya FS. C2orf37 mutational spectrum in Woodhouse-Sakati syndrome patients. <span><span class="ref-journal">Clin Genet. </span>2010;<span class="ref-vol">78</span>:585&ndash;90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20507343" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 20507343</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.albanese.2015.1547">Albanese A, Romito LM, Calandrella D. Therapeutic advances in dystonia. <span><span class="ref-journal">Mov Disord. </span>2015;<span class="ref-vol">30</span>:1547&ndash;56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26301801" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 26301801</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.ali.2016.263">Ali RH, Shah K, Nasir A, Steyaert W, Coucke PJ, Ahmad W. Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome (WSS). <span><span class="ref-journal">Clin Genet. </span>2016;<span class="ref-vol">90</span>:263&ndash;9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26612766" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 26612766</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.alsemari.2007.149">Al-Semari A, Bohlega S. Autosomal-recessive syndrome with alopecia, hypogonadism, progressive extra-pyramidal disorder, white matter disease, sensory neural deafness, diabetes mellitus, and low IGF1. <span><span class="ref-journal">Am J Med Genet A. </span>2007;<span class="ref-vol">143A</span>:149&ndash;60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17167799" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 17167799</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.alswailem.2006.116">Al-Swailem SA, Al-Assiri AA, Al-Torbak AA. Woodhouse Sakati syndrome associated with bilateral keratoconus. <span><span class="ref-journal">Br J Ophthalmol. </span>2006;<span class="ref-vol">90</span>:116&ndash;7.</span> [<a href="/pmc/articles/PMC1856898/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1856898</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16361682" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 16361682</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.benomran.2011.2647">Ben-Omran T, Ali R, Almureikhi M, Alameer S, Al-Saffar M, Walsh CA, Felie JM, Teebi A. Phenotypic heterogeneity in Woodhouse-Sakati syndrome: two new families with a mutation in the C2orf37 gene. <span><span class="ref-journal">Am J Med Genet A. </span>2011;<span class="ref-vol">155A</span>:2647&ndash;53.</span> [<a href="/pmc/articles/PMC6905109/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC6905109</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21964978" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 21964978</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.bohlega.2019.99">Bohlega S, Abusrair AH, Al-Ajlan FS, Alharbi N, Al-Semari A, Bohlega B, Abualsaud D, Alkuraya F. Patterns of neurological manifestations in Woodhouse-Sakati syndrome. <span><span class="ref-journal">Parkinsonism Relat Disord. </span>2019 Dec;<span class="ref-vol">69</span>:99&ndash;103.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31726291" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 31726291</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.crowell.2016.22">Crowell JL, Shah BB. Surgery for dystonia and tremor. <span><span class="ref-journal">Curr Neurol Neurosci Rep. </span>2016;<span class="ref-vol">16</span>:22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26838349" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 26838349</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.habib.2011.26">Habib R, Basit S, Khan S, Khan MN, Ahmad W. A novel splice site mutation in gene C2orf37 underlying Woodhouse-Sakati syndrome (WSS) in a consanguineous family of Pakistani origin. <span><span class="ref-journal">Gene. </span>2011;<span class="ref-vol">490</span>:26&ndash;31.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21963443" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 21963443</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.j_nsson.2017.519">J&#x000f3;nsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519&ndash;22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.koshy.2008.57">Koshy G, Danda S, Thomas N, Mathews V, Viswanathan V. Three siblings with Woodhouse-Sakati syndrome in an Indian family. <span><span class="ref-journal">Clin Dysmorphol. </span>2008;<span class="ref-vol">17</span>:57&ndash;60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18049083" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18049083</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.lee.2020.1024">Lee JH, Yun JY, Gregory A, Hogarth P, Hayflick SJ. Brain MRI pattern recognition in neurodegeneration with brain iron accumulation. <span><span class="ref-journal">Front Neurol. </span>2020;<span class="ref-vol">11</span>:1024.</span> [<a href="/pmc/articles/PMC7511538/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC7511538</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33013674" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 33013674</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.leh_ricy.2020.462">Leh&#x000e9;ricy S, Roze E, Goizet C, Mochel F. MRI of neurodegeneration with brain iron accumulation. <span><span class="ref-journal">Curr Opin Neurol. </span>2020;<span class="ref-vol">33</span>:462&ndash;73.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32657887" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 32657887</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.nanda.2014.83">Nanda A, Pasternack SM, Mahmoudi H, Ishorst N, Grimalt R, Betz RC. Alopecia and hypotrichosis as characteristic findings in Woodhouse-Sakati syndrome: report of a family with mutation in the C2orf37 gene. <span><span class="ref-journal">Pediatr Dermatol. </span>2014;<span class="ref-vol">31</span>:83&ndash;7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24015686" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 24015686</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.rachmiel.2011.362">Rachmiel M, Bistritzer T, Hershkoviz E, Khahil A, Epstein O, Parvari R. Woodhouse-Sakati syndrome in an Israeli-Arab family presenting with youth-onset diabetes mellitus and delayed puberty. <span><span class="ref-journal">Horm Res Paediatr. </span>2011;<span class="ref-vol">75</span>:362&ndash;6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21304230" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 21304230</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.schneider.2008.592">Schneider SA, Bhatia KP. Dystonia in the Woodhouse Sakati syndrome: A new family and literature review. <span><span class="ref-journal">Mov Disord. </span>2008;<span class="ref-vol">23</span>:592&ndash;6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18175354" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 18175354</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.steindl.2010.594">Steindl K, Alazami AM, Bhatia KP, Wuerfel JT, Petersen D, Cartolari R, Neri G, Klein C, Mongiardo B, Alkuraya FS, Schneider SA. A novel C2orf37 mutation causes the first Italian cases of Woodhouse Sakati syndrome. <span><span class="ref-journal">Clin Genet. </span>2010;<span class="ref-vol">78</span>:594&ndash;7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21044051" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 21044051</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="wss.REF.woodhouse.1983.216">Woodhouse NJ, Sakati NA. A syndrome of hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and ECG abnormalities. <span><span class="ref-journal">J Med Genet. </span>1983;<span class="ref-vol">20</span>:216&ndash;9.</span> [<a href="/pmc/articles/PMC1049050/" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pmc">PMC free article<span class="bk_prnt">: PMC1049050</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/6876115" ref="pagearea=cite-ref&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=pubmed">PubMed<span class="bk_prnt">: 6876115</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK378974_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Saeed A Bohlega</span>, MD, FRCPC, FAAN<div class="affiliation small">Professor and Consultant, Department of Neurosciences
King Faisal Specialist Hospital and Research Center
Riyadh, Saudi Arabia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="as.ude.crhsfk@agelohob" class="oemail">as.ude.crhsfk@agelohob</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Ali Abusrair</span>, MD<div class="affiliation small">Neurologist, Department of Neurosciences
King Faisal Specialist Hospital and Research Center
Riyadh, Saudi Arabia<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="as.vog.hom@riarsubaa" class="oemail">as.vog.hom@riarsubaa</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">August 4, 2016</span>; Last Update: <span itemprop="dateModified">July 8, 2021</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> &#x000a9; 1993-2025, University of Washington, Seattle. GeneReviews is
a registered trademark of the University of Washington, Seattle. All rights
reserved.<p class="small">GeneReviews&#x000ae; chapters are owned by the University of Washington. Permission is
hereby granted to reproduce, distribute, and translate copies of content materials for
noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">http://www.genereviews.org/</a>) and copyright (&#x000a9; 1993-2025 University of
Washington) are included with each copy; (ii) a link to the original material is provided
whenever the material is published elsewhere on the Web; and (iii) reproducers,
distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">GeneReviews&#x000ae; Copyright Notice and Usage
Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
of GeneReviews chapters for use in lab reports and clinic notes are a permitted
use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">GeneReviews&#x000ae; Copyright Notice and Usage
Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&amp;targetsite=external&amp;targetcat=link&amp;targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Bohlega SA, Abusrair A. Woodhouse-Sakati Syndrome. 2016 Aug 4 [Updated 2021 Jul 8]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews&#x000ae; [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/whs/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/x-ag/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobwssTmoleculargenetictestingusedin"><div id="wss.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Woodhouse-Sakati Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene&#x000a0;<sup>1</sup></th><th id="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants&#x000a0;<sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
<i>DCAF17</i>
</td><td headers="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis&#x000a0;<sup>3</sup></td><td headers="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td></tr><tr><td headers="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis&#x000a0;<sup>4</sup></td><td headers="hd_h_wss.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="wss.TF.1.1"><p class="no_margin">See <a href="/books/NBK378974/?report=reader#wss.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="wss.TF.1.2"><p class="no_margin">See <a href="#wss.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="wss.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="wss.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobwssTdisordersphenotypestoconsiderin"><div id="wss.T.disordersphenotypes_to_consider_in" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Disorders/Phenotypes to Consider in the Differential Diagnosis of Woodhouse-Sakati Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.disordersphenotypes_to_consider_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.disordersphenotypes_to_consider_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s) / Genetic Mechanism</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrine Findings</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alopecia</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic Findings &#x00026; MRI</th><th id="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ANOS1</i><br /><i>CHD7</i><br /><i>FGFR1</i><br /><i>GNRHR</i><br /><i>IL17RD</i><br /><i>PROKR2</i><br /><i>SOX10</i><br /><i>TACR3</i>&#x000a0;<sup>1</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/kms/?report=reader">Isolated GnRH deficiency</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL<br />AD<br />AR</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Idiopathic hypogonadotropic hypogonadism</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">&#x02013;</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ataxia, epilepsy, &#x00026; congenital paresis of cranial nerves III, IV, VI<br />In IGD: typically, normal-appearing hypothalamus &#x00026; pituitary on MRI.<br />In KS: typically, aplasia or hypoplasia of the olfactory bulbs/sulci/tracts.</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">&#x000b1; Congenital olfactory deficit (KS)</td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ATP13A2</i>
<br />
<a href="/books/n/gene/mt-mpan/?report=reader">C19orf12</a>
<br />
<i>COASY</i>
<br />
<a href="/books/n/gene/acp/?report=reader">CP</a>
<br />
<a href="/books/n/gene/fahn/?report=reader">FA2H</a>
<br />
<a href="/books/n/gene/neuroferritin/?report=reader">FTL</a>
<br />
<a href="/books/n/gene/pkan/?report=reader">PANK2</a>
<br />
<a href="/books/n/gene/inad/?report=reader">PLA2G6</a>
<br />
<a href="/books/n/gene/bpan/?report=reader">WDR45</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/nbia-ov/?report=reader">Neurodegeneration w/brain iron storage disorders</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR<br />XL<br />AD&#x000a0;<sup>2</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dystonia w/postural instability; brain iron accumulation on MRI</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable phenotype &#x00026; variable age of onset</td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>CLPP</i>
<br />
<i>ERAL1</i>
<br />
<i>HARS2</i>
<br />
<i>HSD17B4</i>
<br />
<i>LARS2</i>
<br />
<i>TWNK</i>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/perrault/?report=reader">Perrault syndrome</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early SNHL, learning difficulties, DD, cerebellar ataxia, motor &#x00026; sensory peripheral neuropathy</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Heterogeneous &#x00026; variable; premature ovarian failure</td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>ERCC6</i>
<br />
<i>ERCC8</i>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/cockayne/?report=reader">Cockayne syndrome</a> type III</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">&#x02013;</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature &#x00026; appearance of premature aging</td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>LMNA</i>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/hgps/?report=reader">Hutchinson-Gilford progeria syndrome</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD&#x000a0;<sup>3</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Affected persons do not become sexually mature. Insulin resistance w/o overt development of diabetes mellitus in ~50%</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal motor &#x00026; mental development</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Aged-looking skin, joint abnormalities, &#x00026; loss of subcutaneous fat; conductive hearing loss</td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<i>RBM28</i>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Alopecia, neuropathy, endocrinopathy syndrome (OMIM <a href="http://omim.org/entry/612079" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">612079</a>)&#x000a0;<sup>4</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypogonadotropic hypogonadism &#x00026; adrenal insufficiency</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">+</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cognitive impairment</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>RNF216</i><br /><i>PNPLA6</i>&#x000a0;<sup>5</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gordon Holmes syndrome (OMIM <a href="http://omim.org/entry/212840" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">212840</a>)</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypogonadotropic hypogonadism</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">&#x02013;</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebellar ataxia &#x00026; (to a variable degree) brisk reflexes; white matter lesions</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>TIMM8A</i><br />delXp22.1&#x000a0;<sup>6</sup></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="/books/n/gene/ddon/?report=reader">Deafness-dystonia-optic neuronopathy syndrome</a>
</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XL</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">&#x02013;</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Early-onset SNHL; movement disorder; dementia (onset age ~40 yrs); psychiatric symptoms may appear in childhood &#x00026; progress.</td><td headers="hd_h_wss.T.disordersphenotypes_to_consider_in_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Impaired vision &#x00026; behavior problems; occurs almost exclusively in males.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">&#x02013; = not associated with this disorder; + = associated with this disorder; AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; GnRH gonadotropin-releasing hormone; IGD = isolated gonadotropin-releasing hormone deficiency; KS = Kallmann syndrome; MOI = mode of inheritance; SNHL = sensorineural hearing loss; XL = X-linked</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="wss.TF.2.1"><p class="no_margin">Listed genes represent the most common genetic causes; see <a href="/books/n/gene/kms/?report=reader">Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency</a> for other, less commonly involved genes.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="wss.TF.2.2"><p class="no_margin">Eight of the ten genetically defined types of neurodegeneration with brain iron accumulation are inherited in an autosomal recessive manner. Exceptions are: <a href="/books/n/gene/bpan/?report=reader">beta-propeller protein-associated neurodegeneration</a>, caused by <i>de novo</i> pathogenic variants in <i>WDR45</i>, which is inherited in an X-linked manner with suspected male lethality; and <a href="/books/n/gene/neuroferritin/?report=reader">neuroferritinopathy</a>, caused by pathogenic variants in <i>FTL</i>, which is inherited in an autosomal dominant manner.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="wss.TF.2.3"><p class="no_margin">Almost all individuals with Hutchinson-Gilford progeria syndrome have the disorder as the result of a <i>de novo</i> autosomal dominant pathogenic variant.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="wss.TF.2.4"><p class="no_margin">Only one family reported to date according to OMIM</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="wss.TF.2.5"><p class="no_margin">See <a href="/books/n/gene/pnpla6-dis/?report=reader"><i>PNPLA6</i>-Related Disorders</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="wss.TF.2.6"><p class="no_margin">The diagnosis of deafness-dystonia-optic neuronopathy is established in either a male proband who has a hemizygous <i>TIMM8A</i> pathogenic variant or a female proband who has a heterozygous <i>TIMM8A</i> pathogenic variant or a contiguous gene deletion of Xp22.1 involving <i>TIMM8A</i>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobwssTrecommendedevaluationsfollowing"><div id="wss.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Woodhouse-Sakati Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wss.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Endocrine</b>
</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<ul><li class="half_rhythm"><div>Ask about menstrual cycle (women) or sexual dysfunction (men) to screen for hypogonadism.</div></li><li class="half_rhythm"><div>Serum IGF-1</div></li><li class="half_rhythm"><div>Fasting glucose level, hemoglobin A1c, or oral glucose tolerance test</div></li><li class="half_rhythm"><div>Thyroid function studies incl TSH &#x00026; free T4</div></li></ul>
</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for endocrine findings: hypogonadism, low IGF-1, diabetes mellitus, hypothyroidism</td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<p>
<b>Ectodermal</b>
</p>
</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment of scalp hair</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_1" rowspan="5" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
<p>
<b>Neurologic</b>
</p>
</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic exam for evidence of dystonia (See <a href="/books/n/gene/dystonia-ov/?report=reader">Dystonia Overview</a>.)</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Speech &#x00026; language assessment of dysarthria &#x00026; dysphagia</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment of hearing (See <a href="/books/n/gene/deafness-overview/?report=reader">Hereditary Hearing Loss and Deafness</a>.)</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment of psychomotor development</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In young children</td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Assessment of intellectual ability</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">In persons age &#x0003e;6 yrs</td></tr><tr><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Genetic</b>
<br />
<b>counseling</b>
</td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals&#x000a0;<sup>1</sup></td><td headers="hd_h_wss.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform patients &#x00026; their families re nature, MOI, &#x00026; implications of WSS in order to facilitate medical &#x00026; personal decision making</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="wss.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobwssTtreatmentofmanifestationsinind"><div id="wss.T.treatment_of_manifestations_in_ind" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Woodhouse-Sakati Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.treatment_of_manifestations_in_ind/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.treatment_of_manifestations_in_ind_lrgtbl__"><table><thead><tr><th id="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Hypogonadism</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sex hormone replacement therapy at usual age of puberty to induce &#x00026; maintain secondary sex characteristics &#x00026; promote bone health.</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard replacement hormonal treatment will not promote fertility. It may be possible to stimulate testes w/gonadotropins &#x00026; harvest sperm w/assisted reproductive technology.</td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Low IGF-1</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment w/recombinant IGF-1 is not recommended: no evidence that it improves clinical features of WSS [<a class="bibr" href="#wss.REF.agopiantz.2014.1" rid="wss.REF.agopiantz.2014.1">Agopiantz et al 2014</a>].</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">IGF-1 levels may &#x02191; w/sex hormone replacement therapy.</td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Diabetes mellitus</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Hypothyroidism</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">L-thyroxine replacement therapy</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Sparse hair</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment is symptomatic &#x00026; cosmetic only.</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Dystonia</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><b>Oral medications</b> are usually tried first:
<ul><li class="half_rhythm"><div>Anticholinergics (e.g., trihexyphenidyl) are moderately effective in 40%-50%.</div></li><li class="half_rhythm"><div>Baclofen (Lioresal<sup>&#x000ae;</sup>)</div></li><li class="half_rhythm"><div>Benzodiazepines, especially clonazepam</div></li><li class="half_rhythm"><div>Other medications tried alone or in combination w/the above: levodopa, carbamazepine, &#x00026; dopamine depleting agents (reserpine, tetrabenazine)</div></li></ul>
<b>Botulinum toxin</b> injections directly into dystonic muscles are generally the treatment of choice for adult-onset focal dystonias. For those w/more widespread dystonia in whom specific muscle groups produce disabling symptoms, such injections may also be helpful &#x00026; are often used in combination w/oral medications.</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<ul><li class="half_rhythm"><div>Trihexyphenidyl can be titrated to high doses (~100 mg/day) in younger persons.</div></li><li class="half_rhythm"><div>Anticholinergic side effects, esp cognitive effects, must be monitored closely.</div></li><li class="half_rhythm"><div>If medications fail, surgery to enable deep-brain stimulation of the globus pallidus interna has been an effective treatment for some forms of medically refractory primary generalized dystonia [<a class="bibr" href="#wss.REF.crowell.2016.22" rid="wss.REF.crowell.2016.22">Crowell &#x00026; Shah 2016</a>]. Its use in WSS has not been documented.</div></li></ul>
</td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Dysarthria</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consultation w/a speech therapist may be helpful.</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Dysphagia</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<ul><li class="half_rhythm"><div>Oral secretions in those w/bulbar symptoms can be &#x02193; w/tricylic antidepressants &#x00026; anticholinergic agents, thus reducing need for suctioning.</div></li><li class="half_rhythm"><div>Swallowing difficulties can be alleviated by thickening liquids &#x00026; pureeing solid food, &#x00026; eventually using a gastrostomy tube to help maintain caloric intake &#x00026; hydration.</div></li><li class="half_rhythm"><div>Nutritional mgmt by a knowledgeable nutritionist is helpful.</div></li></ul>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Sensorineural</b>
<br />
<b>hearing loss</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="/books/n/gene/deafness-overview/?report=reader">Hereditary Hearing Loss and Deafness</a> for mgmt.</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Intellectual</b>
<br />
<b>disability</b>
</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Educational support services as needed</td><td headers="hd_h_wss.T.treatment_of_manifestations_in_ind_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobwssTrecommendedsurveillanceforindiv"><div id="wss.T.recommended_surveillance_for_indiv" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Woodhouse-Sakati Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.recommended_surveillance_for_indiv/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.recommended_surveillance_for_indiv_lrgtbl__"><table><thead><tr><th id="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Endocrine</b>
</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ask about menstrual cycle (women) or sexual dysfunction (men) to screen for hypogonadism.</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 12-14 yrs</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Screening for type 2 diabetes mellitus by standard clinical assays incl fasting glucose level, hemoglobin A1c, or oral glucose tolerance test</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 20 yrs</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Thyroid function studies to incl TSH &#x00026; free T4</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Serum IGF-1</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3-5 yrs</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
<b>Neurologic</b>
</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for dystonia</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Speech &#x00026; language assessment for dysarthria &#x00026; dysphagia</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually throughout childhood</td></tr><tr><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Audiology eval</td><td headers="hd_h_wss.T.recommended_surveillance_for_indiv_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobwssmolgenTA"><div id="wss.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Woodhouse-Sakati Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_wss.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_wss.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_wss.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_wss.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_wss.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_wss.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_wss.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="/gene/80067" ref="pagearea=body&amp;targetsite=entrez&amp;targetcat=link&amp;targettype=gene">
<i>DCAF17</i>
</a>
</td><td headers="hd_b_wss.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&#x00026;acc=80067" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">2q31<wbr style="display:inline-block"></wbr>&#8203;.1</a>
</td><td headers="hd_b_wss.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="http://www.uniprot.org/uniprot/Q5H9S7" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">DDB1- and CUL4-associated factor 17</a>
</td><td headers="hd_b_wss.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="http://databases.lovd.nl/shared/genes/DCAF17" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">DCAF17 database</a>
</td><td headers="hd_b_wss.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DCAF17" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">DCAF17</a>
</td><td headers="hd_b_wss.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=DCAF17[gene]" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">DCAF17</a>
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="wss.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
<a href="http://www.genenames.org/index.html" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">HGNC</a>;
chromosome locus from
<a href="http://www.omim.org/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">OMIM</a>;
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">UniProt</a>.
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobwssmolgenTB"><div id="wss.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Woodhouse-Sakati Syndrome (<a href="/omim/241080,612515" ref="pagearea=body&amp;targetsite=entrez&amp;targetcat=term&amp;targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
<a href="/omim/241080" ref="pagearea=body&amp;targetsite=entrez&amp;targetcat=term&amp;targettype=omim">241080</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">WOODHOUSE-SAKATI SYNDROME; WDSKS</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
<a href="/omim/612515" ref="pagearea=body&amp;targetsite=entrez&amp;targetcat=term&amp;targettype=omim">612515</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DDB1- AND CUL4-ASSOCIATED FACTOR 17; DCAF17</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobwssTnotabledcaf17pathogenicvariants"><div id="wss.T.notable_dcaf17_pathogenic_variants" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Notable <i>DCAF17</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK378974/table/wss.T.notable_dcaf17_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wss.T.notable_dcaf17_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_025000.4" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NM_025000<wbr style="display:inline-block"></wbr>&#8203;.4</a>
<br />
<a href="/protein/NP_079276.2" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NP_079276<wbr style="display:inline-block"></wbr>&#8203;.2</a>
</td><td headers="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.436delC&#x000a0;<sup>1</sup></td><td headers="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala147HisfsTer9</td><td headers="hd_h_wss.T.notable_dcaf17_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Saudi Arabian &#x00026; Qatari populations [<a class="bibr" href="#wss.REF.alazami.2008.684" rid="wss.REF.alazami.2008.684">Alazami et al 2008</a>, <a class="bibr" href="#wss.REF.benomran.2011.2647" rid="wss.REF.benomran.2011.2647">Ben-Omran et al 2011</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="http://varnomen.hgvs.org/" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">varnomen<wbr style="display:inline-block"></wbr>&#8203;.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="wss.TF.6.1"><p class="no_margin">This variant has the same nucleotide and protein change designations for either transcript variant <a href="/nuccore/NM_025000.4" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NM_025000<wbr style="display:inline-block"></wbr>&#8203;.4</a> or <a href="/nuccore/NM_001164821.1" ref="pagearea=body&amp;targetsite=external&amp;targetcat=link&amp;targettype=uri">NM_001164821<wbr style="display:inline-block"></wbr>&#8203;.1</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobwssF1"><div id="wss.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK378974/bin/wss-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Affected individuals from different families with WSS who have variable degrees of alopecia or hair loss and neurologic involvement</p><p>A. Male age 23 with flat occiput; temporal and frontal alopecia</p><p>B. Female age 19 with dystonia involving neck, face, mouth, and tongue, arms, and hands</p><p>C. Female age 35 with sparse, short hair, flat occiput, low-set ears, and retrocollis</p><p>D. Male age 14 with sparse hair</p><p>E. Female age 25 with alopecia and wasting of the facial and temporal muscles</p><p>F. Male age 17 with dystonic posturing and lack of breast tissue</p><p>G. Male age 21 with sparse hair with temporal hair loss; long face</p><p>H. Male age 32 with severe generalized dystonia with alopecia totalis</p></div></div></article><article data-type="fig" id="figobwssF2"><div id="wss.F2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK378974/bin/wss-Image002.jpg" alt="Figure 2. . Brain MRI of individuals with WSS." /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>Brain MRI of individuals with WSS. Arrows indicate the following findings:</p><p>A. Sagittal T<sub>1</sub>-weighted image, showing small pituitary gland and partially empty sella.</p><p>B-C. Fluid-attenuated inversion recovery (FLAIR) demonstrating variable degrees of white matter signal intensities at different stages of the disease.</p><p>D. T<sub>2</sub>*-weighted MRI showing iron deposition in the globus pallidus.</p><p>E-F. Diffusion-weighted imaging (DWI) showing diffusion restriction involving the splenium of the corpus callosum.</p></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
<!-- Book content -->
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal105 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
</html>