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<meta name="ncbi_db" content="books" /><meta name="ncbi_pdid" content="book-part" /><meta name="ncbi_acc" content="NBK1190" /><meta name="ncbi_domain" content="gene" /><meta name="ncbi_report" content="record" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meta name="ncbi_pcid" content="/NBK1190/" /><meta name="ncbi_pagename" content="Duane Syndrome - GeneReviews® - NCBI Bookshelf" /><meta name="ncbi_bookparttype" content="chapter" /><meta name="ncbi_app" content="bookshelf" />
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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Duane Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2019/08/29" /><meta name="citation_author" content="Brenda J Barry" /><meta name="citation_author" content="Mary C Whitman" /><meta name="citation_author" content="David G Hunter" /><meta name="citation_author" content="Elizabeth C Engle" /><meta name="citation_pmid" content="20301369" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1190/" /><meta name="citation_keywords" content="Duane Anomaly, Isolated" /><meta name="citation_keywords" content="Duane Retraction Syndrome" /><meta name="citation_keywords" content="Stilling-Turk-Duane Syndrome" /><meta name="citation_keywords" content="Duane Retraction Syndrome" /><meta name="citation_keywords" content="Stilling-Turk-Duane Syndrome" /><meta name="citation_keywords" content="Duane Anomaly, Isolated" /><meta name="citation_keywords" content="N-chimaerin" /><meta name="citation_keywords" content="Sal-like protein 4" /><meta name="citation_keywords" content="Transcription factor MafB" /><meta name="citation_keywords" content="CHN1" /><meta name="citation_keywords" content="MAFB" /><meta name="citation_keywords" content="SALL4" /><meta name="citation_keywords" content="Duane Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Duane Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Brenda J Barry" /><meta name="DC.Contributor" content="Mary C Whitman" /><meta name="DC.Contributor" content="David G Hunter" /><meta name="DC.Contributor" content="Elizabeth C Engle" /><meta name="DC.Date" content="2019/08/29" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1190/" /><meta name="description" content="Duane syndrome is a strabismus condition clinically characterized by congenital non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined syndromic diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome." /><meta name="og:title" content="Duane Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Duane syndrome is a strabismus condition clinically characterized by congenital non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined syndromic diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1190/" /><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/duane/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1190/" /><link rel="stylesheet" href="/corehtml/pmc/css/figpopup.css" type="text/css" media="screen" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css" /><link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_print.min.css" type="text/css" media="print" /><style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style><script type="text/javascript" src="/corehtml/pmc/js/jquery.hoverIntent.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/common.min.js?_=3.18"> </script><script type="text/javascript" src="/corehtml/pmc/js/large-obj-scrollbars.min.js"> </script><script type="text/javascript">window.name="mainwindow";</script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/book-toc.min.js"> </script><script type="text/javascript" src="/corehtml/pmc/js/bookshelf/2.26/books.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script><meta name="book-collection" content="NONE" />
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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="All GeneReviews" href="/books/n/gene/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png" alt="Cover of GeneReviews®" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>GeneReviews<sup>®</sup> [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK1190_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK1190_dtls__"><div>Adam MP, Feldman J, Mirzaa GM, et al., editors.</div><div>Seattle (WA): <a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>; 1993-2025.</div></div><div class="half_rhythm"><ul class="inline_list"><li style="margin-right:1em"><a class="bk_cntns" href="/books/n/gene/">GeneReviews by Title</a></li></ul></div><div class="bk_noprnt"><form method="get" action="/books/n/gene/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search GeneReviews" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search GeneReviews" submit="false" style="padding: 0.1em 0.4em;" /></div></form><div><ul class="inline_list"><li><a href="/books/n/gene/advanced/">GeneReviews Advanced Search</a></li><li style="margin-left:.5em"><a href="/books/n/gene/helpadvsearch/">Help</a></li></ul></div></div></div><div class="icnblk_cntnt two_col"><div class="pagination bk_noprnt"><a class="active page_link prev" href="/books/n/gene/dbh/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/duarte-gal/" title="Next page in this title">Next ></a></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK1190_"><span class="title" itemprop="name">Duane Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonyms: Duane Anomaly, Isolated; Duane Retraction Syndrome; Stilling-Turk-Duane Syndrome</div><p class="contrib-group"><span itemprop="author">Brenda J Barry</span>, MS, <span itemprop="author">Mary C Whitman</span>, MD, PhD, <span itemprop="author">David G Hunter</span>, MD, PhD, and <span itemprop="author">Elizabeth C Engle</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK1190_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK1190_ai__"><div class="contrib half_rhythm"><span itemprop="author">Brenda J Barry</span>, MS<div class="affiliation small">Research Specialist II, Boston Children's Hospital<br />Department of Neurology, Harvard Medical School<br />Boston, Massachusetts</div><div class="affiliation small">Howard Hughes Medical Institute<br />Chevy Chase, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.dravrah.snerdlihc@2yrrab.adnerb" class="oemail">ude.dravrah.snerdlihc@2yrrab.adnerb</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Mary C Whitman</span>, MD, PhD<div class="affiliation small">Assistant Professor of Ophthalmology, Boston Children's Hospital<br />Harvard Medical School<br />Boston, Massachusetts<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.dravrah.snerdlihc@namtihw.yram" class="oemail">ude.dravrah.snerdlihc@namtihw.yram</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">David G Hunter</span>, MD, PhD<div class="affiliation small">Ophthalmologist-in-Chief, Boston Children's Hospital<br />Professor of Ophthalmology, Harvard Medical School<br />Boston, Massachusetts<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.dravrah.snerdlihc@retnuh.divad" class="oemail">ude.dravrah.snerdlihc@retnuh.divad</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Elizabeth C Engle</span>, MD<div class="affiliation small">Howard Hughes Medical Institute<br />Chevy Chase, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.dravrah.snerdlihc@elgne.htebazile" class="oemail">ude.dravrah.snerdlihc@elgne.htebazile</a></div></div><div class="affiliation small">Senior Associate in Neurology and Ophthalmology, Boston Children's Hospital<br />Professor of Neurology and Ophthalmology, Harvard Medical School<br />Boston, Massachusetts</div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">May 25, 2007</span>; Last Update: <span itemprop="dateModified">August 29, 2019</span>.</p><p><em>Estimated reading time: 33 minutes</em></p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="duane.Summary" itemprop="description"><h2 id="_duane_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Duane syndrome is a strabismus condition clinically characterized by <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of Duane syndrome is usually made by an ophthalmologist based on clinical findings. More than 98% of individuals with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome and no family history lack an identified genetic etiology. Molecular genetic testing for a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>CHN1</i>, <i>MAFB</i>, or <i>SALL4</i> is most appropriate for those with a positive family history of isolated Duane syndrome (although <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> pathogenic variants in these genes have been detected in some <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases) and for those with clinical ocular findings designated as type I or type III Duane syndrome.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Spectacles or contact lenses for refractive error; occlusion or penalization of the better-seeing eye for treatment of amblyopia; prism glasses (usually in older individuals with mild involvement) to improve the compensatory head position; extraocular muscle surgery to address alignment in primary gaze, compensatory head posture, and upshoot or downshoot.</p><p><i>Prevention of secondary complications:</i> Amblyopia therapy to prevent vision loss in the less preferred eye; extraocular muscle surgery to prevent loss of binocular vision in individuals who abandon the compensatory head posture and allow strabismus to become manifest, and to prevent neck muscle problems in those with large compensatory head postures.</p><p><i>Surveillance:</i> Ophthalmologic visits every three to six months during the first years of life to prevent, detect, and treat amblyopia; annual or biannual examinations once the presence of binocular vision and reduced risk for amblyopia is confirmed, and in all individuals older than age seven to 12; no surveillance in adulthood beyond public health guidelines.</p><p><i>Evaluation of relatives at risk:</i> Eye examination within the first year of life so that early diagnosis and treatment can prevent secondary complications.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>The majority of individuals with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome represent <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (i.e., a single occurrence in a family), with a positive family history apparent for only approximately 10% of affected individuals. Duane syndrome resulting from a <i>CHN1, MAFB,</i> or <i>SALL4</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. Most individuals with isolated <i>CHN1-</i>, <i>MAFB-</i>, or <i>SALL4-</i>related Duane syndrome have the disorder as the result of a pathogenic variant inherited from an affected parent. Each child of an individual with Duane syndrome resulting from an identified pathogenic variant has a 50% chance of inheriting the variant. Prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible once the causative pathogenic variant has been identified in an affected family member.</p></div></div><div id="duane.Diagnosis"><h2 id="_duane_Diagnosis_">Diagnosis</h2><p>Duane syndrome is a strabismus condition clinically characterized by <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The diagnosis of Duane syndrome is based on clinical findings and classified into three types (see <a href="/books/NBK1190/table/duane.T.clinical_findings_comparison_of/?report=objectonly" target="object" rid-ob="figobduaneTclinicalfindingscomparisonof">Table 1</a>).</p><p>Most affected individuals with Duane syndrome have <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome (i.e., they do not have other detected <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies). Other individuals fall into well-defined <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> diagnoses (see <a href="#duane.Genetically_Related_Allelic_Disord">Genetically Related Disorders</a> and <a href="#duane.Differential_Diagnosis">Differential Diagnosis</a>). However, many individuals with Duane syndrome have non-ocular findings that are not classified as a particular syndrome; they are included in this review for completeness.</p><p>The vast majority of individuals with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome represent <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (i.e., a single occurrence in a family). A positive family history showing <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance is apparent for approximately 10% of affected individuals [<a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</p><div id="duane.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Duane syndrome, a <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a>, non-progressive eye movement disorder, <b>should be suspected</b> in individuals who present with the following features:</p><ul><li class="half_rhythm"><div>Congenital limited horizontal eye movement with impairment of abduction and/or adduction</div></li><li class="half_rhythm"><div>Globe retraction (co-contraction) accompanied by narrowing of the palpebral fissure (i.e., reduced distance between the upper and lower eyelids) on adduction.</div></li></ul><p>Note: Adduction is movement of the globe toward the midline (the nose); abduction is movement of the globe toward the ear, away ("abducted") from the midline.</p></div><div id="duane.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p><b>Clinical findings.</b> The diagnosis of Duane syndrome <b>is established</b>
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<b>in</b> a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> typically by an ophthalmologist by detection of the specific clinical findings of limited abduction and/or adduction in association with globe retraction on adduction. Individuals can usually be categorized within the three types detailed below, though there may be some overlap among these categories.</p><div id="duane.T.clinical_findings_comparison_of" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Clinical Findings: Comparison of Duane Syndrome Types I-III</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.clinical_findings_comparison_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.clinical_findings_comparison_of_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Finding</th><th id="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Type I (~75%-80% of cases)</th><th id="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Type II (~1%-5%)</th><th id="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Type III (~10%-20%)</th></tr></thead><tbody><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Abduction</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absent to markedly restricted</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal to mildly restricted</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absent to markedly restricted</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Adduction</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Normal to mildly restricted</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absent to markedly restricted</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Absent to markedly restricted</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Globe retraction & palpebral fissure narrowing</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Present on adduction</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Present on adduction</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Present on adduction or attempted adduction</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Upshoot & downshoot of affected globe on adduction</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variably present; more common than in types I or II</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Primary gaze</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Esotropia, variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exotropia, variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Esotropia more common than exotropia, variably present</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anomalous head posture / head turn</b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Turn towards involved side, variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Turn towards uninvolved side, variably present</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Turn towards involved side, variably present</td></tr><tr><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Laterality <sup>1</sup></b>
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</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unilateral or bilateral</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unilateral or bilateral</td><td headers="hd_h_duane.T.clinical_findings_comparison_of_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unilateral or bilateral</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Note: An alternative simpler classification is to note the deviation in primary gaze (esotropic or exotropic Duane syndrome) and specify whether there is limitation of adduction, abduction, or both.</p></div></dd><dt>1. </dt><dd><div id="duane.TF.1.1"><p class="no_margin">The eye findings are more likely to be bilateral in <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> cases and in those in whom a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified in one of the known associated genes [<a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</p></div></dd></dl></div></div></div><p><b>Molecular genetic testing</b> (see <a href="/books/NBK1190/table/duane.T.molecular_genetic_testing_used_i/?report=objectonly" target="object" rid-ob="figobduaneTmoleculargenetictestingusedi">Table 2</a>) is most appropriate for those individuals with:</p><ul><li class="half_rhythm"><div>A positive family history of Duane syndrome.</div><ul><li class="half_rhythm"><div>After finding a <i>CHN1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in seven of 20 families with Duane syndrome, <a class="bk_pop" href="#duane.REF.miyake.2010.215">Miyake et al [2010]</a> screened 140 individuals with Duane syndrome with a negative family history and failed to identify a <i>CHN1</i> pathogenic variant in any individual. Of note, a suspected disease-causing <i>CHN1</i> variant was identified in an affected individual lacking a positive family history [<a class="bk_pop" href="#duane.REF.biler.2017.472">Biler et al 2017</a>], but such reports are rare.</div></li><li class="half_rhythm"><div><a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al [2016]</a> studied 401 individuals with Duane syndrome and found a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>MAFB</i> in four probands. Three of the probands had a positive family history; in the fourth the pathogenic variant was <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>. Also, in one of the <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> pedigrees, the <i>de novo</i> nature of the pathogenic variant was determined for the original <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>, who had unaffected parents.</div></li><li class="half_rhythm"><div>Due to <a class="def" href="/books/n/gene/glossary/def-item/variable-expressivity/">variable expressivity</a>, individuals with a <i>SALL4</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> may present with apparently <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome themselves [<a class="bk_pop" href="#duane.REF.albaradie.2002.1195">Al-Baradie et al 2002</a>, <a class="bk_pop" href="#duane.REF.yang.2013.986">Yang et al 2013</a>], though they may have a positive family history of <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> Duane syndrome.</div></li></ul></li><li class="half_rhythm"><div>Bilateral Duane syndrome. The eye findings are more likely to be bilateral in <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> cases and in those in whom a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is identified in one of the known associated genes [<a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</div></li><li class="half_rhythm"><div>Duane syndrome type I or type III or a combination of those types. Duane syndrome type II has not been observed in those with a positive family history or in individuals with pathogenic variants in the identified genes, suggesting a distinct etiology [<a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</div></li></ul><p>Molecular genetic testing approaches can include <b>concurrent or serial single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b>, use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>, and <b>more comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Concurrent single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>CHN1</i>, <i>MAFB</i>, and <i>SALL4</i> is performed first, and followed by gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> of <i>MAFB</i> and <i>SALL4</i> if no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found.</div><div class="half_rhythm">Note: (1) If serial <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> analysis is to be performed for <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome, <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> <i>CHN1</i> is performed first, followed by sequence analysis of <i>MAFB</i> and gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> if no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> is found. The exception to this would be if there was evidence of hearing loss in addition to Duane syndrome, in which case <i>MAFB</i> followed by <i>CHN1</i> would be more appropriate. If the causative variant is not identified, <i>SALL4</i> sequencing and gene-targeted deletion/duplication analysis should be considered. (2) Since <i>CHN1-</i>related disease occurs through a <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> mechanism and large intragenic deletion or duplication has not been reported, testing for <i>CHN1</i> intragenic deletions or duplication is unlikely to identify a disease-causing variant.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>A <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>CHN1</i>, <i>MAFB</i>, <i>SALL4</i>, and other genes of interest (see <a href="#duane.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> and pathogenic variants in genes that do not explain the underlying <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Note: (1) The genes included in the panel and the diagnostic <a class="def" href="/books/n/gene/glossary/def-item/sensitivity/">sensitivity</a> of the testing used for each <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused <a class="def" href="/books/n/gene/glossary/def-item/exome/">exome</a> analysis that includes genes specified by the clinician. (4) Methods used in a panel may include <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>, <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a>, and/or other non-sequencing-based tests.</div><div class="half_rhythm">For an introduction to multigene panels click <a href="/books/n/gene/app5/#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/#app5.Multigene_Panels_FAQs">here</a>.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>More comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (when available) including <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> and <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a> may be considered. Such testing (which does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>[s] are likely involved) may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).</div><div class="half_rhythm">If <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a> is not diagnostic, <b><a class="def" href="/books/n/gene/glossary/def-item/exome-array/">exome array</a></b> (when clinically available) may be considered to detect (multi)<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications that cannot be detected by <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a>.</div><div class="half_rhythm">For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</div></li></ul><div id="duane.T.molecular_genetic_testing_used_i" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Duane Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.molecular_genetic_testing_used_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.molecular_genetic_testing_used_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1, 2</sup></th><th id="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of Duane Syndrome Attributed to Pathogenic Variants in Gene</th><th id="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>3</sup> Identified by Method</th></tr><tr><th headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>4</sup></th><th headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3" id="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></th></tr></thead><tbody><tr><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CHN1</i>
|
||
</td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Familial: up to 15% <sup>6</sup><br />Simplex: rare <sup>7</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99% <sup>6, 7</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td></tr><tr><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MAFB</i>
|
||
</td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Familial: 4% <sup>9, 10</sup><br />Simplex: rare <sup>9</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">3/4 <sup>9</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1/4 <sup>9</sup></td></tr><tr><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SALL4</i>
|
||
</td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Familial: very rare <sup>11</sup><br />Simplex: not reported <sup>11</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">≤80% <sup>11, 12</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10%-15% <sup>13</sup></td></tr><tr><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Familial: ~80% <sup>14</sup><br />Simplex: >90% <sup>14</sup></td><td headers="hd_h_duane.T.molecular_genetic_testing_used_i_1_1_1_3 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_1 hd_h_duane.T.molecular_genetic_testing_used_i_1_1_2_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="duane.TF.2.1"><p class="no_margin">Genes are listed in alphabetic order.</p></div></dd><dt>2. </dt><dd><div id="duane.TF.2.2"><p class="no_margin">See <a href="/books/NBK1190/#duane.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>3. </dt><dd><div id="duane.TF.2.3"><p class="no_margin">See <a href="#duane.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>.</p></div></dd><dt>4. </dt><dd><div id="duane.TF.2.4"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants and small intragenic deletions/insertions; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>5. </dt><dd><div id="duane.TF.2.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications.</p></div></dd><dt>6. </dt><dd><div id="duane.TF.2.6"><p class="no_margin">Probands with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> Duane syndrome described in: <a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al [2008]</a>, <a class="bk_pop" href="#duane.REF.volk.2010.1351">Volk et al [2010]</a>, <a class="bk_pop" href="#duane.REF.chan.2011.649">Chan et al [2011]</a>, <a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al [2011]</a>, <a class="bk_pop" href="#duane.REF.biler.2017.472">Biler et al [2017]</a></p></div></dd><dt>7. </dt><dd><div id="duane.TF.2.7"><p class="no_margin">Probands with a family history negative for Duane syndrome described in <a class="bk_pop" href="#duane.REF.miyake.2010.215">Miyake et al [2010]</a>, <a class="bk_pop" href="#duane.REF.volk.2010.1351">Volk et al [2010]</a>, and <a class="bk_pop" href="#duane.REF.biler.2017.472">Biler et al [2017]</a>; however, pathogenicity of disease-associated variants was not proven for all variants.</p></div></dd><dt>8. </dt><dd><div id="duane.TF.2.8"><p class="no_margin">No data on detection rate of <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> are available; however, since <i>CHN1</i> pathogenic variants act through a <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> mechanism, detection of large deletions or duplication is unlikely.</p></div></dd><dt>9. </dt><dd><div id="duane.TF.2.9"><p class="no_margin"><a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al [2016]</a> studied 401 probands with Duane syndrome and found a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>MAFB</i> in four probands with Duane syndrome; in three individuals the condition was <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> and in the fourth the pathogenic variant was <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a>. In one of the familial cases, hearing loss was present with the Duane syndrome in three of the four affected family members in three generations. In an additional ten <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases with Duane syndrome and hearing loss, no pathogenic variant in <i>MAFB</i> was identified.</p></div></dd><dt>10. </dt><dd><div id="duane.TF.2.10"><p class="no_margin">Three of 77 individuals with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> Duane syndrome had a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>MAFB</i> [Authors, personal observation].</p></div></dd><dt>11. </dt><dd><div id="duane.TF.2.11"><p class="no_margin">Isolated Duane syndrome was observed in one of eight and one of four affected individuals in two families with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>SALL4</i> detected on <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> [<a class="bk_pop" href="#duane.REF.albaradie.2002.1195">Al-Baradie et al 2002</a>, <a class="bk_pop" href="#duane.REF.yang.2013.986">Yang et al 2013</a>]. A study of 25 individuals with nonfamilial <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome did not identify pathogenic variants on sequence analysis of <i>SALL4</i> [<a class="bk_pop" href="#duane.REF.wabbels.2004.216">Wabbels et al 2004</a>].</p></div></dd><dt>12. </dt><dd><div id="duane.TF.2.12"><p class="no_margin"><a class="bk_pop" href="#duane.REF.albaradie.2002.1195">Al-Baradie et al [2002]</a>, <a class="bk_pop" href="#duane.REF.kohlhase.2002.2979">Kohlhase et al [2002]</a>, <a class="bk_pop" href="#duane.REF.kohlhase.2003.473">Kohlhase et al [2003]</a>, <a class="bk_pop" href="#duane.REF.borozdin.2004b.e102">Borozdin et al [2004b]</a>, <a class="bk_pop" href="#duane.REF.kohlhase.2005.176">Kohlhase et al [2005]</a></p></div></dd><dt>13. </dt><dd><div id="duane.TF.2.13"><p class="no_margin"><a class="bk_pop" href="#duane.REF.borozdin.2004a.e113">Borozdin et al [2004a]</a>, <a class="bk_pop" href="#duane.REF.borozdin.2007.830">Borozdin et al [2007]</a></p></div></dd><dt>14. </dt><dd><div id="duane.TF.2.14"><p class="no_margin"><a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al [2008]</a>, <a class="bk_pop" href="#duane.REF.volk.2010.1351">Volk et al [2010]</a>, <a class="bk_pop" href="#duane.REF.chan.2011.649">Chan et al [2011]</a>, <a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al [2011]</a>, <a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al [2016]</a>, <a class="bk_pop" href="#duane.REF.biler.2017.472">Biler et al [2017]</a>. In the cohort described by the authors, 98% of <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a>, <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome lacked an identified genetic etiology.</p></div></dd></dl></div></div></div><p>Note: The testing recommendations in this section are for individuals with Duane syndrome, either <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> or with one or more non-ocular anomalies that do not constitute an established or recognizable syndrome. If an individual presents with Duane syndrome plus significant anomalies that suggest the possibility of a <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> abnormality, testing with chromosome microarray analysis (CMA) can be considered.</p></div></div><div id="duane.Clinical_Characteristics"><h2 id="_duane_Clinical_Characteristics_">Clinical Characteristics</h2><div id="duane.Clinical_Description"><h3>Clinical Description</h3><p>Duane syndrome is a strabismus condition clinically characterized by <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly is due to failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle, with globe retraction occurring due to abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Affected individuals may also have upshoot or downshoot of the affected eye on attempted adduction. For reasons yet to be determined, the left side is more commonly affected; this is supported by the authors' internal data showing that the left side is affected in 70% of unilateral cases [<a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>; <a class="bk_pop" href="#duane.REF.kekunnaya.2012.164">Kekunnaya et al 2012</a>; Authors, unpublished observation].</p><p>Duane syndrome is often reported as more common in females than in males, particularly in unilateral and <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases [<a class="bk_pop" href="#duane.REF.kekunnaya.2012.164">Kekunnaya et al 2012</a>, <a class="bk_pop" href="#duane.REF.graeber.2013.427">Graeber et al 2013</a>, <a class="bk_pop" href="#duane.REF.kekunnaya.2017.1917">Kekunnaya & Negalur 2017</a>]. Internal data reveal that 56% of individuals with unilateral Duane syndrome are female and 51% of simplex cases are female [Authors, unpublished observation].</p><p>Restriction in vertical movement of the eyes may also be found in some individuals with Duane syndrome, depending on the associated <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> (see <a href="#duane.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>).</p><p><b>Strabismus</b> is the misalignment of the line of sight of the two eyes. Many individuals with Duane syndrome have strabismus in primary gaze; esotropia is more common in Duane syndrome type I and exotropia in Duane syndrome type II.</p><ul><li class="half_rhythm"><div>Although esotropia is more common in most studies, a recent report found that nearly a third of individuals with Duane syndrome seen at a tertiary care center in south India had exotropia [<a class="bk_pop" href="#duane.REF.bhate.2017.117">Bhate et al 2017</a>].</div></li><li class="half_rhythm"><div>While movement of the affected eye is impaired, when the contralateral eye is able to move freely, it allows individuals with strabismus in primary gaze to use a compensatory head turn in order to align the eyes, thus avoiding diplopia and preserving single binocular vision.</div></li></ul><p><b>Amblyopia</b> occurs in approximately 10% of individuals with Duane syndrome; these persons are typically a subset of those with Duane syndrome who lack binocular vision. The amblyopia in Duane syndrome responds to standard therapy if detected early; if not treated early in life, the vision loss from amblyopia is irreversible.</p><p><b>Visual acuity</b> is good except in those individuals with amblyopia.</p><p><b>Other dysinnervation phenomena</b> may occur in individuals with Duane syndrome<b>.</b> These include:</p><ul><li class="half_rhythm"><div>Infraduction of the affected eye in attempted lateral gaze; this occurs in the majority of cases [<a class="bk_pop" href="#duane.REF.rhiu.2018.171">Rhiu et al 2018</a>.] The phenomenon is more likely to be observed in more severely affected individuals.</div></li><li class="half_rhythm"><div>Marcus Gunn jaw-winking phenomenon (upper eyelid movement/fluttering each time the jaw opens and closes) [<a class="bk_pop" href="#duane.REF.isenberg.1983.235">Isenberg & Blechman 1983</a>, <a class="bk_pop" href="#duane.REF.oltmanns.2010">Oltmanns & Khuddus 2010</a>, <a class="bk_pop" href="#duane.REF.gupta.2014.135">Gupta et al 2014</a>].</div></li><li class="half_rhythm"><div>An exaggerated oculo-auricular phenomenon (coactivation of external ear muscles during lateral gaze) [<a class="bk_pop" href="#duane.REF.gilbert.2017.165">Gilbert & Hunter 2017</a>].</div></li><li class="half_rhythm"><div>Crocodile tears (tearing with chewing due to aberrant facial salivary fibers innervating the lacrimal gland) [<a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</div></li></ul><p><b>Neuroimaging.</b> Orbital and brain stem MRI of affected members of two pedigrees with <i>CHN1</i> pathogenic variants did not visualize the abducens nerve in most affected individuals and revealed structurally abnormal lateral rectus muscles in some. The oculomotor and optic nerves were also small [<a class="bk_pop" href="#duane.REF.demer.2007.194">Demer et al 2007</a>]. Decreased superior oblique muscle volume has also been observed on MRI in individuals with <i>CHN1</i> pathogenic variants, supporting trochlear nerve hypoplasia [<a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al 2011</a>].</p><p>Magnetic resonance imaging (MRI) in <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases (without a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in any known <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>) has verified the absence or severe hypoplasia of the abducens nerve, often with normal appearance of the lateral rectus muscle [<a class="bk_pop" href="#duane.REF.demer.2006.135">Demer et al 2006</a>].</p></div><div id="duane.Pathophysiology"><h3>Pathophysiology</h3><p>It is generally believed that Duane syndrome results from maldevelopment of motor neurons in the abducens nucleus and aberrant innervation of the lateral rectus muscle [<a class="bk_pop" href="#duane.REF.y_ksel.2010.2334">Yüksel et al 2010</a>]. Early studies of Duane syndrome reported fibrosis of the lateral rectus or medial rectus muscles, and suggested a primary myopathic etiology for this disorder [<a class="bk_pop" href="#duane.REF.matteucci.1946.345">Matteucci 1946</a>]. Subsequently, several postmortem examinations of individuals with <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> Duane syndrome revealed absence of the abducens motor neurons and ipsilateral cranial nerve VI, and partial innervation of the lateral rectus muscle(s) by branches from the oculomotor nerve [<a class="bk_pop" href="#duane.REF.hotchkiss.1980.870">Hotchkiss et al 1980</a>, <a class="bk_pop" href="#duane.REF.miller.1982.1468">Miller et al 1982</a>]. Electromyography revealed simultaneous activation of the medial and lateral rectus muscles, supporting co-contraction of these two horizontal muscles as the cause of the globe retraction [<a class="bk_pop" href="#duane.REF.scott.1972.140">Scott & Wong 1972</a>].</p><p>The decreased superior oblique muscle volume observed on MRI, supporting trochlear nerve hypoplasia, leads to the suggestion that Duane syndrome resulting from pathogenic variants in <i>CHN1</i> represents a <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cranial dysinnervation disorder that results from errors not only in abducens, but also trochlear and oculomotor axon pathfinding [<a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al 2011</a>].</p><p>Animal models of both <i>CHN1</i> and <i>MAFB</i> pathogenic variants support a neurogenic cause of Duane syndrome. In <i>CHN1</i>-related mouse models, axons of the abducens nerve stall, then retract and die, and the lateral rectus is subsequently innervated by branches from the oculomotor nerve [<a class="bk_pop" href="#duane.REF.nugent.2017.1664">Nugent et al 2017</a>]. In <i>Mafb</i>-knockout mice, the abducens nucleus does not form, and the lateral rectus muscle is innervated by branches from the oculomotor nerve [<a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al 2016</a>].</p></div><div id="duane.Other_Anomalies"><h3>Other Anomalies</h3><p>Most affected individuals with Duane syndrome have <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome without other <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies. Published estimates of individuals with other systemic findings range from lows of under 10% [<a class="bk_pop" href="#duane.REF.kekunnaya.2012.164">Kekunnaya et al 2012</a>] to just over 50% [<a class="bk_pop" href="#duane.REF.marshman.2000.106">Marshman et al 2000</a>]. Far fewer individuals have a constellation of anomalies that falls within recognizable <a class="def" href="/books/n/gene/glossary/def-item/syndromic/">syndromic</a> patterns which are often inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> pattern. In the authors' cohort, approximately 30% of all individuals with a diagnosis of Duane syndrome have non-ocular systemic findings. When individuals who fall within the spectrum of <i>SALL-4</i> related disorders are removed, 25% of individuals have syndromic findings [Authors, unpublished data].</p><p>From the authors' unpublished data, 26.7% of individuals with Duane syndrome who do not have a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in any of the currently known associated genes have non-ocular findings, ranging from minor anomalies such as preauricular tags to more severe conditions such as Hirschsprung disease.</p></div><div id="duane.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p><b><i>CHN1</i>.</b> Individuals with pathogenic variants in <i>CHN1</i> are more likely to have bilateral involvement, vertical movement abnormalities beyond the upshoot and downshoot often seen in Duane syndrome, and a positive family history when compared to individuals with Duane syndrome who do not have a <i>CHN1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> [<a class="bk_pop" href="#duane.REF.chung.2000.500">Chung et al 2000</a>, <a class="bk_pop" href="#duane.REF.demer.2007.194">Demer et al 2007</a>, <a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al 2008</a>, <a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al 2011</a>].</p><p><b><i>MAFB</i>.</b> Individuals with pathogenic variants in <i>MAFB</i> are more likely to have bilateral Duane syndrome and may have mild-to-severe sensorineural hearing loss in addition to the Duane syndrome. Hearing loss was documented in one of four reported pedigrees of otherwise <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome, and confirmed in three of four individuals in that family [<a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al 2016</a>].</p><p><b><i>SALL4.</i></b> Individuals thus far reported with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome associated with <i>SALL4</i> pathogenic variants have family members with <a href="/books/n/gene/drrs/">Duane-radial ray syndrome</a> [<a class="bk_pop" href="#duane.REF.albaradie.2002.1195">Al-Baradie et al 2002</a>, <a class="bk_pop" href="#duane.REF.yang.2013.986">Yang et al 2013</a>]. The eye condition tends to be bilateral rather than unilateral in individuals with <i>SALL4</i> variants [<a class="bk_pop" href="#duane.REF.kohlhase.2005.176">Kohlhase et al 2005</a>].</p></div><div id="duane.Penetrance"><h3>Penetrance</h3><p>Families with Duane syndrome in whom a <i>CHN1</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified may have reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> [<a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al 2008</a>, <a class="bk_pop" href="#duane.REF.chan.2011.649">Chan et al 2011</a>].</p><p>There has been no evidence of reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> in the limited number of families with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome identified with <i>MAFB</i> or <i>SALL4</i> pathogenic variants [<a class="bk_pop" href="#duane.REF.yang.2013.986">Yang et al 2013</a>, <a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al 2016</a>]</p></div><div id="duane.Nomenclature"><h3>Nomenclature</h3><p>Duane syndrome is named for the ophthalmologist Alexander Duane (1858-1926).</p><p>Historically, Duane syndrome was initially proposed to be myogenic in origin. Electromyography of the extraocular muscles, postmortem examinations, and MRI, however, now support a neurogenic etiology [<a class="bk_pop" href="#duane.REF.demer.2007.194">Demer et al 2007</a>]. This is also supported by developmental studies of mouse models [<a class="bk_pop" href="#duane.REF.nugent.2017.1664">Nugent et al 2017</a>] and has led to the proposed renaming of Duane syndrome as the "co-contractive retraction syndrome" (types 1-3) [<a class="bk_pop" href="#duane.REF.hertle.2002.201">Hertle 2002</a>] and classification as one of the <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cranial dysinnervation disorders [<a class="bk_pop" href="#duane.REF.gutowski.2003.573">Gutowski et al 2003</a>, <a class="bk_pop" href="#duane.REF.engle.2006.343">Engle 2006</a>].</p></div><div id="duane.Prevalence"><h3>Prevalence</h3><p>Duane syndrome accounts for 1%-5% of all cases of strabismus.</p><p>Isolated Duane syndrome in <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> and <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases has been identified worldwide. The prevalence of Duane syndrome is estimated at between 1:1,000 and 1:10,000 in the general population [<a class="bk_pop" href="#duane.REF.y_ksel.2010.2334">Yüksel et al 2010</a>, <a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>]</p></div></div><div id="duane.Genetically_Related_Allelic_Disord"><h2 id="_duane_Genetically_Related_Allelic_Disord_">Genetically Related (Allelic) Disorders</h2><p><b><i>CHN1.</i></b> Pathogenic <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> variants in <i>CHN1</i> have also been identified in individuals with vertical strabismus and supraduction deficits in the absence of Duane retraction syndrome [<a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al 2011</a>].</p><p><b><i>MAFB.</i></b> Missense <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> variants in <i>MAFB</i> have previously been identified in individuals with multicentric carpotarsal osteolysis [<a class="bk_pop" href="#duane.REF.zankl.2012.494">Zankl et al 2012</a>] and noncoding variants have been reported in individuals with cleft lip and/or cleft palate [<a class="bk_pop" href="#duane.REF.beaty.2010.525">Beaty et al 2010</a>].</p><p><b><i>SALL4</i>.</b>
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<a href="/books/n/gene/drrs/"><i>SALL4</i>-related disorders</a> include a spectrum of phenotypes previously thought to be distinct entities including Duane-radial ray syndrome or Okihiro syndrome, acro-renal-ocular syndrome, and <i>SALL4</i>-related Holt-Oram syndrome.</p></div><div id="duane.Differential_Diagnosis"><h2 id="_duane_Differential_Diagnosis_">Differential Diagnosis</h2><p><b>Duane syndrome with associated <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies.</b> Approximately 30% of individuals with Duane syndrome have other congenital anomalies, particularly of the ear, kidney, heart, upper limbs, and skeleton. These associated anomalies are typically reported in <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> cases, but also occur together with Duane syndrome as <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> malformation or genetic syndromes.</p><div id="duane.T.disorders_to_consider_in_the_dif" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Disorders to Consider in the Differential Diagnosis of Duane Syndrome with Associated Congenital Anomalies</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.disorders_to_consider_in_the_dif/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.disorders_to_consider_in_the_dif_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of Disorder (in addition to Duane syndrome)</th></tr></thead><tbody><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/tbs/">Townes-Brocks syndrome</a>
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</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SALL1</i>
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</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Anal, ear, limb & renal anomalies</div></li><li class="half_rhythm"><div>Additional ophthalmic findings: coloboma, ptosis, epibulbar dermoid, & crocodile tears</div></li></ul>
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</td></tr><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/hoxa1-dis/"><i>HOXA1</i>-related disorders</a> (Bosley-Salih-Alorainy syndrome, Athabascan brain stem dysgenesis syndrome)</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>HOXA1</i>
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</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Note: Ocular findings are usually Duane syndrome type III or horizontal gaze palsy</div></li><li class="half_rhythm"><div>Bilateral sensorineural hearing loss caused by absent cochlea & rudimentary inner-ear development</div></li><li class="half_rhythm"><div>Subsets of individuals manifest ID, autism, moderate-to-severe central hypoventilation, facial weakness, swallowing difficulties, vocal cord paresis, conotruncal heart defects, & skull & craniofacial abnormalities</div></li></ul>
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</td></tr><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Wildervanck syndrome (cervicooculoacoustic syndrome) (OMIM <a href="https://omim.org/entry/314600" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">314600</a>)</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>1</sup></td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>1</sup></td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Deafness</div></li><li class="half_rhythm"><div>Klippel-Feil anomaly (fused cervical vertebrae)</div></li></ul>
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</td></tr><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Goldenhar syndrome<br />(hemifacial microsomia, oculoauriculovertebral spectrum) (OMIM <a href="https://omim.org/entry/164210" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">164210</a>)</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sporadic<br />AD<br />AR</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Craniofacial, ocular, cardiac, vertebral, & CNS defects, consistent w/maldevelopment of the 1st & 2nd branchial arches</td></tr><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Chromosome 8 anomalies</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sporadic</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 2.</td></tr><tr><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> anomalies</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">NA</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sporadic</td><td headers="hd_h_duane.T.disorders_to_consider_in_the_dif_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnotes 3 & 4.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; CNS = central nervous system; ID = intellectual disability; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; NA = not applicable</p></div></dd><dt>1. </dt><dd><div id="duane.TF.3.1"><p class="no_margin">Most Wildervanck syndrome is <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> and limited to females. A case report describes a male with Wildervanck syndrome and a 3-kb <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> at Xq26.3 encompassing one <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>, <i>FGF13,</i> which encodes a protein that acts intracellularly in neurons throughout brain development [<a class="bk_pop" href="#duane.REF.abuamero.2014.18">Abu-Amero et al 2014</a>].</p></div></dd><dt>2. </dt><dd><div id="duane.TF.3.2"><p class="no_margin">Several individuals with Duane syndrome have been reported to have <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> 8 anomalies: anomalies of the 8q13 DURS1 <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> (OMIM <a href="https://omim.org/entry/126800" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">126800</a>); mosaic trisomy 8 (2 separate reports); <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a> 8q13-q21.2; a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> reciprocal balanced <a class="def" href="/books/n/gene/glossary/def-item/translocation/">translocation</a> consisting of t(6:8)(q26;q13) disrupting <i>CPAH</i>, the <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> for carboxypeptidase; and a <a class="def" href="/books/n/gene/glossary/def-item/duplication/">duplication</a> (or microduplication) of 8q12 [<a class="bk_pop" href="#duane.REF.lehman.2009.436">Lehman et al 2009</a>, <a class="bk_pop" href="#duane.REF.amouroux.2012.580">Amouroux et al 2012</a>, <a class="bk_pop" href="#duane.REF.baroncini.2013.49">Baroncini et al 2013</a>] and 8p11.2 deletion [<a class="bk_pop" href="#duane.REF.abuamero.2015.99">Abu-Amero et al 2015</a>]. Three reports suggest that abnormal dosage of <i>CHD7</i> may cause the resultant <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> on 8q12. Individuals described in these case reports manifest Duane syndrome with various associated <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> abnormalities including other cranial nerve deficits, facial dysmorphisms, intellectual disabilities, and cardiac defects.</p></div></dd><dt>3. </dt><dd><div id="duane.TF.3.3"><p class="no_margin">Other <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> aberrations associated with Duane syndrome have been reported to involve 2q13, 4q27-31, 6p25, 7, 10q24.2q26.3, 12q24.31, 19q13.4, 20q13.12, and 22pter-q13.31. Duane syndrome has been described in one individual with 48,XXYY syndrome and another with atypical Silver-Russell syndrome, Duane syndrome, and maternal <a class="def" href="/books/n/gene/glossary/def-item/uniparental-disomy/">uniparental disomy</a> of chromosome 7.</p></div></dd><dt>4. </dt><dd><div id="duane.TF.3.4"><p class="no_margin">Individuals with Duane syndrome and associated <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> defects should be evaluated further for possible underlying chromosomal rearrangements.</p></div></dd></dl></div></div></div><p><b>Other <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> cranial dysinnervation disorders.</b> The term congenital cranial dysinnervation disorders (CCDDs) refers to disorders of innervation of cranial musculature [<a class="bk_pop" href="#duane.REF.gutowski.2003.573">Gutowski et al 2003</a>]. The ocular CCDDs are also included in the category of complex or incomitant strabismus, in which the degree of misalignment of the eyes varies with the direction of gaze.</p><p>Duane syndrome is the most common of the CCDDs. Other ocular CCDDs include those in <a href="/books/NBK1190/table/duane.T.other_congenital_cranial_dysinne/?report=objectonly" target="object" rid-ob="figobduaneTothercongenitalcranialdysinne">Table 4</a>.</p><div id="duane.T.other_congenital_cranial_dysinne" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Other Congenital Cranial Dysinnervation Disorders to Consider in the Differential Diagnosis of Duane Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.other_congenital_cranial_dysinne/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.other_congenital_cranial_dysinne_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_2" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Disorder</th></tr><tr><th headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4" id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/Duane syndrome</th><th headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4" id="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from Duane syndrome</th></tr></thead><tbody><tr><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/cfeom/">Congenital fibrosis of the extraocular muscles</a> <sup>1</sup></td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>KIF21A</i>
|
||
<br />
|
||
<i>PHOX2A</i>
|
||
<br />
|
||
<i>TUBB2B</i>
|
||
<br />
|
||
<i>TUBB3</i>
|
||
</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br /><p>AR</p></td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Often horizontal gaze restrictions</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ptosis, restricted upgaze</td></tr><tr><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Moebius syndrome<br />(OMIM <a href="https://omim.org/entry/157900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">157900</a>)</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Various</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Horizontal gaze palsy</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Facial weakness, no globe retraction</td></tr><tr><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Horizontal gaze palsy w/<br />progressive scoliosis<br />(OMIM <a href="https://omim.org/entry/607313" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">607313</a>)</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>ROBO3</i>
|
||
</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Horizontal gaze palsy</td><td headers="hd_h_duane.T.other_congenital_cranial_dysinne_1_1_1_4 hd_h_duane.T.other_congenital_cranial_dysinne_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No globe retraction, severe, early onset scoliosis</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">AD = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a>; AR = <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a>; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a></p></div></dd><dt>1. </dt><dd><div id="duane.TF.4.1"><p class="no_margin">Congenital fibrosis of the extraocular muscles (CFEOM) refers to at least seven genetically defined syndromes: CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, and Tukel syndrome.</p></div></dd></dl></div></div></div><p><b>Complex and common forms of strabismus</b> that could be confused with Duane syndrome are shown in <a href="/books/NBK1190/table/duane.T.strabismusassociated_disorders_t/?report=objectonly" target="object" rid-ob="figobduaneTstrabismusassociateddisorderst">Table 5</a>.</p><div id="duane.T.strabismusassociated_disorders_t" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Strabismus-Associated Disorders to Consider in the Differential Diagnosis of Duane Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.strabismusassociated_disorders_t/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.strabismusassociated_disorders_t_lrgtbl__"><table><thead><tr><th id="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of Disorder</th></tr><tr><th headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2" id="hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/Duane syndrome</th><th headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2" id="hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from Duane syndrome</th></tr></thead><tbody><tr><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common strabismus</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Strabismus</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Full eye movements</td></tr><tr><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sixth nerve palsy</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Restricted abduction, may be accompanied by esotropia</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">No globe retraction or fissure narrowing<br />Usually acquired</td></tr><tr><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comitant esotropia w/crossed fixation</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May appear to have abduction limitation</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Full abduction can be elicited if tested monocularly.</td></tr><tr><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Congenital ocular motor apraxia</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May appear to have abduction limitation</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Inability to generate horizontal saccades</td></tr><tr><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Brown syndrome ("superior oblique tendon sheath syndrome")</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May appear to have abduction limitation</td><td headers="hd_h_duane.T.strabismusassociated_disorders_t_1_1_1_2 hd_h_duane.T.strabismusassociated_disorders_t_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Inability to elevate the adducted eye actively or passively</td></tr></tbody></table></div></div></div><div id="duane.Management"><h2 id="_duane_Management_">Management</h2><div id="duane.Evaluations_Following_Initial_Diag"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with Duane syndrome, the following evaluations are recommended if they have not already been completed:</p><ul><li class="half_rhythm"><div>Family history</div></li><li class="half_rhythm"><div>Ophthalmologic examination</div><ul><li class="half_rhythm"><div>Determination of deviation in primary gaze, anomalous head position, and horizontal and vertical gaze restrictions</div></li><li class="half_rhythm"><div>Evaluation for aberrant movements. Globe retraction with narrowing of the palpebral fissure in adduction is the <i>sine qua non</i> of Duane syndrome. Infraduction of the affected eye in attempted abduction is a common finding. Other features sometimes observed include up- and downshoot on adduction and Marcus Gunn jaw winking.</div></li><li class="half_rhythm"><div>Full ophthalmologic exam to assess for refractive errors, amblyopia, or amblyopia risk factors.</div></li></ul></li><li class="half_rhythm"><div>Optional forced duction testing and/or force generation testing in cooperative individuals</div></li><li class="half_rhythm"><div>Photographic documentation to identify changes in the condition and for future review</div></li><li class="half_rhythm"><div>If surgery is planned, consideration of brain and orbital MRI to determine brain stem and orbital anatomy (muscles and nerves)</div></li><li class="half_rhythm"><div>General physical examination to look for systemic anomalies that can be found in individuals with Duane syndrome</div></li><li class="half_rhythm"><div>Hearing evaluation</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor</div></li></ul></div><div id="duane.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>
|
||
<b>Nonsurgical treatment of ophthalmologic findings</b>
|
||
</p><ul><li class="half_rhythm"><div>Refractive errors may be managed with spectacles or contact lenses. Specialist examination is required to detect refractive errors early in life, when affected individuals may be asymptomatic, to prevent amblyopia and avoid compounding the motility problem with a focusing problem.</div></li><li class="half_rhythm"><div>Amblyopia can be treated effectively with occlusion or penalization of the better-seeing eye. Early detection (in the 1st years of life) maximizes the likelihood of a good response to treatment.</div></li><li class="half_rhythm"><div>Prism glasses may improve the compensatory head position in mild cases. They are more likely to be tolerated by older persons.</div></li><li class="half_rhythm"><div>Correction of hypermetropic refractive error in children may reduce the angle of strabismus and thus decrease the angle of head turn.</div></li></ul><p>
|
||
<b>Surgical treatment of ophthalmologic findings (extraocular muscle surgery)</b>
|
||
</p><ul><li class="half_rhythm"><div class="half_rhythm">Surgical intervention is usually pursued when any of the following criteria are met:</div><ul><li class="half_rhythm"><div>Symptomatic compensatory head posture</div></li><li class="half_rhythm"><div>Deviation in primary gaze sufficient to provoke diplopia or amblyopia</div></li><li class="half_rhythm"><div>Disfiguring upshoot or downshoot in adduction</div></li></ul><div class="half_rhythm">Note: Surgery does not generally improve abduction of the affected eye, though transposition procedures may provide partial improvement.</div></li><li class="half_rhythm"><div class="half_rhythm">Tightness of the medial rectus muscle can add to the technical difficulty of the surgical procedure.</div></li><li class="half_rhythm"><div class="half_rhythm">Postoperative overcorrection in side gaze, a common occurrence, can create new-onset diplopia.</div><ul><li class="half_rhythm"><div>In esotropic Duane syndrome, diplopia occurs due to exotropia in gaze away from the affected side.</div></li><li class="half_rhythm"><div>In exotropic Duane syndrome, diplopia occurs due to an increase in esotropia in gaze toward the affected side.</div></li></ul></li></ul><p><b>Principles of surgical approach</b> (reviewed by <a class="bk_pop" href="#duane.REF.kekunnaya.2015.63">Kekunnaya et al [2015]</a> and <a class="bk_pop" href="#duane.REF.doyle.2019.5">Doyle & Hunter [2019]</a>)</p><ul><li class="half_rhythm"><div><b>Esotropic Duane syndrome.</b> Consider recession of the medial rectus muscle or lateral transposition of one or both vertical rectus muscles (with or without simultaneous weakening of the medial rectus muscle by recession or botulinum toxin injections). Vertical rectus muscle transposition may be augmented by simultaneous resection of the transposed muscles or by placing posterior augmentation sutures on the transposed muscles. When globe retraction is mild, recession of the medial rectus muscle may be combined with a modest resection of the lateral rectus muscle. If globe retraction is severe and creates a deformity, consider recession of both the medial and lateral rectus muscles. Contralateral medial rectus recession may be added for large deviations.</div></li><li class="half_rhythm"><div><b>Up- and/or downshoot in adduction.</b> Y-splitting of the lateral rectus muscle reduces upshoot and downshoot in adduction without altering the alignment in primary gaze.</div></li><li class="half_rhythm"><div><b>Exotropic Duane syndrome.</b> Consider recession of the ipsilateral lateral rectus muscle in most cases. In more severe cases, a large lateral rectus recession may be combined with lateral transposition of one or both vertical rectus muscles.</div></li></ul></div><div id="duane.Surveillance"><h3>Surveillance</h3><p>Surveillance is important for prevention of amblyopia, and to treat amblyopia if it occurs.</p><ul><li class="half_rhythm"><div>Routine ophthalmologic visits every three to six months during the first years of life</div></li><li class="half_rhythm"><div>Annual or biannual examinations in affected individuals once the presence of binocular vision and reduced risk for amblyopia is confirmed, and in all individuals older than age seven to 12</div></li><li class="half_rhythm"><div>No surveillance in adulthood beyond public health guidelines</div></li></ul></div><div id="duane.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>Ophthalmologic examination within the first year of life is appropriate in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures. If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in the family is known, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> can be used to clarify the genetic status of at-risk relatives.</p><p>See <a href="#duane.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> purposes.</p></div><div id="duane.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="duane.Genetic_Counseling"><h2 id="_duane_Genetic_Counseling_">Genetic Counseling</h2><p>
|
||
<i>Genetic counseling is the process of providing individuals and families with
|
||
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
||
make informed medical and personal decisions. The following section deals with genetic
|
||
risk assessment and the use of family history and genetic testing to clarify genetic
|
||
status for family members; it is not meant to address all personal, cultural, or
|
||
ethical issues that may arise or to substitute for consultation with a genetics
|
||
professional</i>. —ED.</p><div id="duane.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Typically, Duane syndrome occurs in a single affected family member and the molecular basis of the condition is unknown. Familial Duane syndrome represents about 10% of all Duane syndrome [<a class="bk_pop" href="#duane.REF.gutowski.2015.678">Gutowski & Chilton 2015</a>].</p><p>Duane syndrome resulting from a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>CHN1</i>, <i>MAFB</i>, or <i>SALL4</i> is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div><div id="duane.Risk_to_Family_Members_Autosomal_D"><h3>Risk to Family Members (Autosomal Dominant Inheritance)</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div>Most individuals with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> <i>CHN1</i>, <i>MAFB</i>, or <i>SALL4-</i>related Duane syndrome have the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> inherited from an affected parent.</div></li><li class="half_rhythm"><div>Rarely, an individual with <i>CHN1</i>, <i>MAFB</i>, or <i>SALL4-</i>related Duane syndrome represents a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single affected family member) and has the disorder as the result of a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> found in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> cannot be detected in leukocyte DNA of either parent, possible explanations include a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> pathogenic variant in the proband or <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a parent. Though theoretically possible, no instances of germline mosaicism have been reported.</div></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with Duane syndrome may appear to be negative because of failure to recognize the disorder in family members, reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> (see <a href="#duane.Penetrance">Penetrance</a>), or milder <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Therefore, an apparently negative family history cannot be confirmed unless appropriate ophthalmologic evaluation and/or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have been performed on the parents of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</div></li></ul><p><b>Sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> The risk to sibs of a proband with <a class="def" href="/books/n/gene/glossary/def-item/isolated/">isolated</a> Duane syndrome depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is affected and/or is known to have the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. There may be phenotypic variability within families regarding unilateral vs bilateral involvement or, in <i>CHN1</i>-related Duane syndrome, reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> [<a class="bk_pop" href="#duane.REF.engle.2007.189">Engle et al 2007</a>, <a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al 2008</a>, <a class="bk_pop" href="#duane.REF.chan.2011.649">Chan et al 2011</a>].</div></li><li class="half_rhythm"><div>If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has a known Duane syndrome-related <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> that cannot be detected in the leukocyte DNA of either parent, the <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> to sibs is estimated to be 1% because of the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> [<a class="bk_pop" href="#duane.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the Duane syndrome-related <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> but are clinically unaffected, the risk to the sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at an increased risk for Duane syndrome because of the possibility of reduced <a class="def" href="/books/n/gene/glossary/def-item/penetrance/">penetrance</a> in a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> parent or the theoretic possibility of parental <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a>.</div></li></ul><p><b>Offspring of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>.</b> Each child of an individual with Duane syndrome and an identified <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has a 50% chance of inheriting the pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a>'s parents: if a parent is affected, the parent's family members are at risk.</p></div><div id="duane.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#duane.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>Considerations in families with an apparent <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</b> When neither parent of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> condition has the pathogenic variant or clinical evidence of the disorder, it is likely that the proband has a <i>de novo</i> pathogenic variant. However, possible non-medical explanations including <a class="def" href="/books/n/gene/glossary/def-item/alternate-paternity/">alternate paternity</a> or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.</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/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see <a class="bk_pop" href="#duane.REF.huang.2022.389">Huang et al [2022]</a>.</p></div><div id="duane.Prenatal_Testing_and_Preimplantati"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> for Duane syndrome are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a>. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="duane.Resources"><h2 id="_duane_Resources_">Resources</h2><p>
|
||
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
||
support organizations and/or registries for the benefit of individuals with this disorder
|
||
and their families. GeneReviews is not responsible for the information provided by other
|
||
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/">here</a>.</i></p>
|
||
<ul><li class="half_rhythm"><div>
|
||
<b>National Human Genome Research Institute (NHGRI)</b>
|
||
</div><div>
|
||
<a href="https://www.genome.gov/Genetic-Disorders/Duane-Syndrome" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Learning About Duane Syndrome</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>National Eye Institute</b>
|
||
</div><div><b>Phone:</b> 301-496-5248</div><div><b>Email:</b> 2020@nei.nih.gov</div><div>
|
||
<a href="https://nei.nih.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.nei.nih.gov</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Prevent Blindness America</b>
|
||
</div><div>211 West Wacker Drive</div><div>Suite 1700</div><div>Chicago IL 60606</div><div><b>Phone:</b> 800-331-2020</div><div><b>Email:</b> info@preventblindness.org</div><div>
|
||
<a href="http://www.preventblindness.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.preventblindness.org</a>
|
||
</div></li></ul>
|
||
</div><div id="duane.Molecular_Genetics"><h2 id="_duane_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div id="duane.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Duane Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_duane.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_duane.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_duane.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_duane.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_duane.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_duane.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_duane.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/1123" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>CHN1</i>
|
||
</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1123" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2q31<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/P15882" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">N-chimaerin</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/CHN1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHN1 database</a>
|
||
</td><td headers="hd_b_duane.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=CHN1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHN1</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CHN1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHN1</a>
|
||
</td></tr><tr><td headers="hd_b_duane.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/9935" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>MAFB</i>
|
||
</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=9935" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">20q12</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q9Y5Q3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Transcription factor MafB</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.lovd.nl/MAFB" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MAFB @ LOVD</a>
|
||
</td><td headers="hd_b_duane.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=MAFB" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MAFB</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=MAFB[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MAFB</a>
|
||
</td></tr><tr><td headers="hd_b_duane.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/57167" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>SALL4</i>
|
||
</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=57167" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">20q13<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q9UJQ4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Sal-like protein 4</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/SALL4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SALL4 database</a>
|
||
</td><td headers="hd_b_duane.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=SALL4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SALL4</a>
|
||
</td><td headers="hd_b_duane.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SALL4[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SALL4</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="duane.TFA.1"><p class="no_margin">Data are compiled from the following standard references: <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> from
|
||
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
||
<a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> from
|
||
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
||
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
||
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
||
<a href="/books/n/gene/app1/">here</a>.</p></div></dd></dl></div></div></div><div id="duane.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Duane Syndrome (<a href="/omim/118423,604356,607343,608968,617041" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/118423" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">118423</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CHIMERIN 1; CHN1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/604356" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604356</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DUANE RETRACTION SYNDROME 2; DURS2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/607343" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607343</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SAL-LIKE 4; SALL4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/608968" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608968</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MAF bZIP TRANSCRIPTION FACTOR B; MAFB</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/617041" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">617041</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DUANE RETRACTION SYNDROME 3 WITH OR WITHOUT DEAFNESS; DURS3</td></tr></tbody></table></div></div><div id="duane.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CHN1</i> encodes chimaerin. <i>CHN1</i> has several alternatively spliced transcript variants encoding multiple N-chimaerin <a class="def" href="/books/n/gene/glossary/def-item/isoforms/">isoforms</a>. N-chimaerin has three domains:</p><ul><li class="half_rhythm"><div>N-terminal SH2 <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a></div></li><li class="half_rhythm"><div>C-terminal RhoGAP <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a></div></li><li class="half_rhythm"><div>Central C1 <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> similar to protein kinase C</div></li></ul><p>No pathogenic variants have been identified in the N-terminal SH2 <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a>. The longest isoform <a href="https://www.ncbi.nlm.nih.gov/protein/NP_001813.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001813.1</a> has 459 amino acid residues. All identified pathogenic variants are <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> variants that increase N-chimaerin (α2-chimerin RacGAP) activity. Several pathogenic variants appear to enhance N-chimaerin <a class="def" href="/books/n/gene/glossary/def-item/translocation/">translocation</a> to the cell membrane or enhance its ability to self-associate.</p><p><i>MAFB</i> encodes a 323-amino acid <a class="def" href="/books/n/gene/glossary/def-item/transcription-factor/">transcription factor</a> of the basic leucine zipper (LZ) family. There are three critical functional domains:</p><ul><li class="half_rhythm"><div>Extended homology region (EHR)</div></li><li class="half_rhythm"><div>Basic region (BR) required for DNA binding</div></li><li class="half_rhythm"><div>LZ <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> required for dimerization</div></li></ul><p><i>SALL4</i> encodes sal-like protein 4 (SALL4), a protein essential to several developmental processes [<a class="bk_pop" href="#duane.REF.elling.2006.16319">Elling et al 2006</a>].</p><p><b>Mechanism of disease causation.</b> Several animal models demonstrate that <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> variants in N-chimaerin and partial <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> <i>MAFB</i> variants result in Duane syndrome.</p><p>N-chimaerin:</p><ul><li class="half_rhythm"><div>A chick in vivo system was used to demonstrate that N-chimaerin overactivity results in axons terminated prematurely adjacent to the dorsal rectus muscle [<a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al 2008</a>].</div></li><li class="half_rhythm"><div>Knock-in mice with the p.Leu20Phe <i>Chn1</i> substitution have globe retraction, stalling and death of the abducens nerve, and subsequent misinnervation of the lateral rectus by axons from the oculomotor nerve. By contrast, <i>Chn1</i> knockout mice show initial defasiculation and wandering of the abducens nerve, but a subset of fibers properly innervates the lateral rectus, supporting the hypothesis that Duane syndrome is caused by <a class="def" href="/books/n/gene/glossary/def-item/gain-of-function/">gain-of-function</a> variants [<a class="bk_pop" href="#duane.REF.nugent.2017.1664">Nugent et al 2017</a>].</div></li></ul><p><i>MAFB</i>:</p><ul><li class="half_rhythm"><div>Homozygous <i>Mafb</i> knockout mice: Duane syndrome and inner ear defects, perinatal lethal [<a class="bk_pop" href="#duane.REF.blanchi.2003.1091">Blanchi et al 2003</a>]</div></li><li class="half_rhythm"><div>Heterozygous <i>Mafb</i> knockout mice (50% <i>Mafb</i> function): Duane syndrome, without hearing deficits</div></li><li class="half_rhythm"><div>Homozygous <i>kreisler</i> mice (<50% <i>Mafb</i> function): Duane syndrome and inner ear defects</div></li><li class="half_rhythm"><div>Heterozygous <i>kreisler</i> mice (>50% Mafb function): no <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>.</div></li></ul><p>These allelic series in mice indicate that different tissues have different sensitivity to loss of <i>MAFB</i> function. The sensorineural hearing loss results from common cavity deformities of the inner ear. The combined findings of Duane syndrome and inner-ear anomalies pointed to a disruption of early hindbrain development as found in individuals with pathogenic variants in <i>HOXA1</i> [<a class="bk_pop" href="#duane.REF.tischfield.2005.1035">Tischfield et al 2005</a>] and in <i>Mafb</i> knockout mice [<a class="bk_pop" href="#duane.REF.moriguchi.2006.5715">Moriguchi et al 2006</a>, <a class="bk_pop" href="#duane.REF.yu.2013.e01341">Yu et al 2013</a>]. Loss of 50% of <i>MAFB</i> function perturbs abducens nucleus development and causes Duane syndrome. By contrast, while 50% <i>MAFB</i> function is sufficient for inner ear development, greater than 50% loss causes inner ear defects [<a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al 2016</a>].</p><div id="duane.T.duane_syndrome_notable_pathogeni" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Duane Syndrome: Notable Pathogenic Variants by Gene</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1190/table/duane.T.duane_syndrome_notable_pathogeni/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__duane.T.duane_syndrome_notable_pathogeni_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CHN1</i>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001822.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001822<wbr style="display:inline-block"></wbr>.5</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_001813.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001813<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.378T>G</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ile126Met</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Segregated w/disease but also found at low frequency in the population [<a class="bk_pop" href="#duane.REF.miyake.2008.839">Miyake et al 2008</a>, <a class="bk_pop" href="#duane.REF.chan.2011.649">Chan et al 2011</a>]</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.422C>T</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro141Leu</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.443A>T</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr148Pro</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperactivating variant found to expand phenotypic spectrum to vertical strabismus & supraduction deficits in the absence of Duane syndrome [<a class="bk_pop" href="#duane.REF.miyake.2011.6321">Miyake et al 2011</a>]</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>MAFB</i>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_005461.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_005461<wbr style="display:inline-block"></wbr>.4</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_005452.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_005452<wbr style="display:inline-block"></wbr>.2</a>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.440delG</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly147AlafsTer78</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Isolated Duane syndrome</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.644delA</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln215ArgfsTer10</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> <a class="def" href="/books/n/gene/glossary/def-item/deletion/">deletion</a></td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.803delA</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn268MetfsTer125</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dominant-negative variant assoc w/Duane syndrome & sensorineural hearing loss in 3 of 4 affected family members [<a class="bk_pop" href="#duane.REF.park.2016.1220">Park et al 2016</a>]</td></tr><tr><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>SALL4</i>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_020436.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_020436<wbr style="display:inline-block"></wbr>.4</a>
|
||
<br />
|
||
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_065169.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_065169<wbr style="display:inline-block"></wbr>.1</a>
|
||
</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1919dupT</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Met640IlefsTer25</td><td headers="hd_h_duane.T.duane_syndrome_notable_pathogeni_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Pathogenic variants in <i>SALL4</i> are typically assoc w/other <a href="/books/n/gene/drrs/"><i>SALL4-</i>related disorders</a>.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>.hgvs.org</a>). See <a href="/books/n/gene/app3/">Quick Reference</a> for an explanation of nomenclature.</p></div></dd><dt>1. </dt><dd><div id="duane.TF.6.1"><p class="no_margin">Genes from <a href="/books/NBK1190/table/duane.T.clinical_findings_comparison_of/?report=objectonly" target="object" rid-ob="figobduaneTclinicalfindingscomparisonof">Table 1</a> in alphabetic order.</p></div></dd></dl></div></div></div></div></div><div id="duane.Chapter_Notes"><h2 id="_duane_Chapter_Notes_">Chapter Notes</h2><div id="duane.Author_Notes"><h3>Author Notes</h3><p>Boston Children's Hospital<br />Intellectual and Developmental Disabilities Research Center (IDDRC) <a href="https://www.iddrc.org/index.php" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">website</a></p><p>Department of Neurology, Howard Hughes Medical Institute<br />Engle Laboratory <a href="https://www.childrenshospital.org/research/labs/engle-laboratory" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">website</a></p></div><div id="duane.Author_History"><h3>Author History</h3><p>Caroline V Andrews, MSc; Harvard Medical School (2007-2019)<br />Brenda J Barry, MS (2019-present)<br />Elizabeth C Engle, MD (2007-present)<br />David G Hunter, MD, PhD (2007-present)<br />Mary C Whitman, MD, PhD (2019-present)</p></div><div id="duane.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>29 August 2019 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>19 March 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>5 July 2012 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>18 February 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 May 2007 (me) Review posted live</div></li><li class="half_rhythm"><div>23 February 2007 (ee) Original submission</div></li></ul></div></div><div id="duane.References"><h2 id="_duane_References_">References</h2><div id="duane.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="duane.REF.abuamero.2015.99">Abu-Amero
|
||
KK, Kondkar
|
||
A, Hellani
|
||
AM, Oystreck
|
||
DT, Khan
|
||
AO, Bosley
|
||
TM. Nicotinic receptor mutation in a mildly dysmorphic girl with Duane retraction syndrome.
|
||
Ophthalmic Genet.
|
||
2015;36:99-104.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/24001015" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24001015</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duane.REF.abuamero.2014.18">Abu-Amero
|
||
KK, Kondkar
|
||
AA, Alorainy
|
||
IA, Khan
|
||
AO, Al-Enazy
|
||
LA, Oystreck
|
||
DT, Bosley
|
||
TM. Xq26.3 microdeletion in a male with Wildervanck Syndrome.
|
||
Ophthalmic Genet.
|
||
2014;35:18-24.
|
||
[<a href="https://pubmed.ncbi.nlm.nih.gov/23373430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23373430</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duane.REF.albaradie.2002.1195">Al-Baradie
|
||
R, Yamada
|
||
K, St Hilaire
|
||
C, Chan
|
||
WM, Andrews
|
||
C, McIntosh
|
||
N, Nakano
|
||
M, Martonyi
|
||
EJ, Raymond
|
||
WR, Okumura
|
||
S, Okihiro
|
||
MM, Engle
|
||
EC. Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family.
|
||
Am J Hum Genet.
|
||
2002;71:1195-9.
|
||
[<a href="/pmc/articles/PMC385096/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC385096</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12395297" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12395297</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duane.REF.amouroux.2012.580">Amouroux
|
||
C, Vincent
|
||
M, Blanchet
|
||
P, Puechberty
|
||
J, Schneider
|
||
A, Chaze
|
||
AM, Girard
|
||
M, Tournaire
|
||
M, Jorgensen
|
||
C, Morin
|
||
D, Sarda
|
||
P, Lefort
|
||
G, Geneviève
|
||
D. Duplication 8q12: confirmation of a novel recognizable phenotype with duane retraction syndrome and developmental delay.
|
||
Eur J Hum Genet.
|
||
2012;20:580-3.
|
||
[<a href="/pmc/articles/PMC3330221/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3330221</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22258531" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22258531</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duane.REF.baroncini.2013.49">Baroncini
|
||
A, Bertuzzo
|
||
S, Quarantini
|
||
R, Ricciardelli
|
||
P, Giorda
|
||
R, Bonaglia MC1. 8q12 microduplication including CHD7: clinical report on a new patient with Duane retraction syndrome type 3.
|
||
Mol Cytogenet.
|
||
2013;6:49.
|
||
[<a href="/pmc/articles/PMC4176195/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4176195</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24206642" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24206642</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="duane.REF.beaty.2010.525">Beaty
|
||
TH, Murray
|
||
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK1190/?report=reader">PubReader</a></li><li><a href="/books/NBK1190/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK1190" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK1190" style="display:none" title="Cite this Page"><div class="bk_tt">Barry BJ, Whitman MC, Hunter DG, et al. Duane Syndrome. 2007 May 25 [Updated 2019 Aug 29]. 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id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301534" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> PAX6-Related Aniridia.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> PAX6-Related Aniridia.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Moosajee M, Hingorani M, Moore AT. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li 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