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<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE" /><meta name="citation_inbook_title" content="GeneReviews® [Internet]" /><meta name="citation_title" content="Wiedemann-Steiner Syndrome" /><meta name="citation_publisher" content="University of Washington, Seattle" /><meta name="citation_date" content="2022/05/26" /><meta name="citation_author" content="Sarah E Sheppard" /><meta name="citation_author" content="Fabiola Quintero-Rivera" /><meta name="citation_pmid" content="35617449" /><meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK580718/" /><meta name="citation_keywords" content="KMT2A-Related Neurodevelopmental Disorder" /><meta name="citation_keywords" content="KMT2A-Related Neurodevelopmental Disorder" /><meta name="citation_keywords" content="Histone-lysine N-methyltransferase 2A" /><meta name="citation_keywords" content="KMT2A" /><meta name="citation_keywords" content="Wiedemann-Steiner Syndrome" /><link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /><meta name="DC.Title" content="Wiedemann-Steiner Syndrome" /><meta name="DC.Type" content="Text" /><meta name="DC.Publisher" content="University of Washington, Seattle" /><meta name="DC.Contributor" content="Sarah E Sheppard" /><meta name="DC.Contributor" content="Fabiola Quintero-Rivera" /><meta name="DC.Date" content="2022/05/26" /><meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK580718/" /><meta name="description" content="Wiedemann-Steiner syndrome (WSS) is characterized by developmental delay, intellectual disability, and characteristic facial features, with or without additional congenital anomalies. The facial features include thick eyebrows with lateral flare, vertically narrow and downslanted palpebral fissures, widely spaced eyes, long eyelashes, wide nasal bridge, broad nasal tip, thin vermilion of the upper lip, and thick scalp hair. About 60% of affected individuals have hypertrichosis cubiti ("hairy elbows"), which was once thought to be pathognomic for the syndrome, with a majority having hypertrichosis of other body parts. Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies." /><meta name="og:title" content="Wiedemann-Steiner Syndrome" /><meta name="og:type" content="book" /><meta name="og:description" content="Wiedemann-Steiner syndrome (WSS) is characterized by developmental delay, intellectual disability, and characteristic facial features, with or without additional congenital anomalies. The facial features include thick eyebrows with lateral flare, vertically narrow and downslanted palpebral fissures, widely spaced eyes, long eyelashes, wide nasal bridge, broad nasal tip, thin vermilion of the upper lip, and thick scalp hair. About 60% of affected individuals have hypertrichosis cubiti ("hairy elbows"), which was once thought to be pathognomic for the syndrome, with a majority having hypertrichosis of other body parts. Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies." /><meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK580718/" /><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/wiedemann-steiner/" /><link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK580718/" /><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="#__NBK580718_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK580718_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/white-sutton/" title="Previous page in this title">< Prev</a><a class="active page_link next" href="/books/n/gene/williams/" 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="_NBK580718_"><span class="title" itemprop="name">Wiedemann-Steiner Syndrome</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>KMT2A</i>-Related Neurodevelopmental Disorder</div><p class="contrib-group"><span itemprop="author">Sarah E Sheppard</span>, MD, PhD and <span itemprop="author">Fabiola Quintero-Rivera</span>, MD.</p><a data-jig="ncbitoggler" href="#__NBK580718_ai__" style="border:0;text-decoration:none">Author Information and Affiliations</a><div style="display:none" class="ui-widget" id="__NBK580718_ai__"><div class="contrib half_rhythm"><span itemprop="author">Sarah E Sheppard</span>, MD, PhD<div class="affiliation small">Unit on Vascular Malformations<br />Division of Intramural Research<br />Eunice Kennedy Shriver National Institute of Child Health and Human Development<br />Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin@drappehs.haras" class="oemail">vog.hin@drappehs.haras</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Fabiola Quintero-Rivera</span>, MD<div class="affiliation small">Division of Genetic and Genomic Medicine<br />Departments of Pathology, Laboratory Medicine, and Pediatrics<br />School of Medicine<br />University of California, Irvine;<br />UC Irvine Health<br />Orange, California<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.icu.sh@qaloibaf" class="oemail">ude.icu.sh@qaloibaf</a></div></div></div></div><p class="small">Initial Posting: <span itemprop="datePublished">May 26, 2022</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="wiedemann-steiner.Summary" itemprop="description"><h2 id="_wiedemann-steiner_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Wiedemann-Steiner syndrome (WSS) is characterized by developmental delay, intellectual disability, and characteristic facial features, with or without additional <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies. The facial features include thick eyebrows with lateral flare, vertically narrow and downslanted palpebral fissures, widely spaced eyes, long eyelashes, wide nasal bridge, broad nasal tip, thin vermilion of the upper lip, and thick scalp hair. About 60% of affected individuals have hypertrichosis cubiti ("hairy elbows"), which was once thought to be pathognomic for the syndrome, with a majority having hypertrichosis of other body parts. Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of WSS is established in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with suggestive findings and 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>KMT2A</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Feeding therapy with possible supplemental tube feeding for those with poor weight gain / failure to thrive; growth hormone therapy for those with growth hormone deficiency; thyroid replacement therapy for hypothyroidism; consideration of IVIG therapy in those with low antibody levels; consideration of prophylactic antibiotics in those with frequent infections; stool softeners or osmotic agents for bowel dysfunction; oculoplasty for blepharoptosis; CPAP, BiPAP, or surgical removal of the tonsils and adenoids for those with obstructive sleep apnea; behavioral therapy; standard treatment for epilepsy, developmental delay / intellectual disability, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> hip dysplasia, cervical vertebral fusion, eye anomalies, congenital heart defects, renal anomalies, uterine anomalies, and metabolic bone disease (which may include vitamin D supplementation).</p><p><i>Surveillance</i>: At each visit: measurement of growth parameters; evaluation of nutritional status; assessment for constipation; evaluation for new neurologic features and seizure activity with EEG follow up as indicated; assessment of clinical signs of medullar compression; monitoring for signs/symptoms of arrhythmia; assessment of developmental progress, behavior, and physical skills; monitoring for frequent infections. Dental evaluation every six months after the eruption of primary teeth. Assessment for premature thelarche or primary amenorrhea in childhood until growth/menarche is complete. Ophthalmologic evaluation annually, or as clinically indicated.</p><p><i>Agents/circumstances to avoid:</i> The authors are aware of one individual with WSS who developed hyperammonemia with the use of the anti-seizure medication valproate. While this is not specific to individuals with WSS, valproate should be used with caution.</p><p><i>Pregnancy management</i>: In affected pregnant women who have a seizure disorder, discussion of the most appropriate anti-seizure medication regimen during pregnancy is recommended. Cervical spine anomalies may lead to immobility or instability, which may complicate airway management. Vertebral anomalies or scoliosis in the thoracic or lumbar spine may complicate spinal or epidural anesthesia.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Most individuals diagnosed with WSS whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have the disorder as 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>. Rarely, individuals diagnosed with WSS have an affected parent. In this situation, WSS can be inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> fashion. Each offspring of an individual with WSS is at a 50% risk of being affected. Once the <i>KMT2A</i> pathogenic variant has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p></div></div><div id="wiedemann-steiner.Diagnosis"><h2 id="_wiedemann-steiner_Diagnosis_">Diagnosis</h2><p>No consensus clinical diagnostic criteria for Wiedemann-Steiner syndrome (WSS) have been published.</p><div id="wiedemann-steiner.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Wiedemann-Steiner syndrome <b>should be suspected</b> in individuals with the following clinical, imaging, and family history findings.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>Distinctive facial features (<a class="figpopup" href="/books/NBK580718/figure/wiedemann-steiner.F1/?report=objectonly" target="object" rid-figpopup="figwiedemannsteinerF1" rid-ob="figobwiedemannsteinerF1">Figures 1</a>, <a class="figpopup" href="/books/NBK580718/figure/wiedemann-steiner.F2/?report=objectonly" target="object" rid-figpopup="figwiedemannsteinerF2" rid-ob="figobwiedemannsteinerF2">2</a>, <a class="figpopup" href="/books/NBK580718/figure/wiedemann-steiner.F3/?report=objectonly" target="object" rid-figpopup="figwiedemannsteinerF3" rid-ob="figobwiedemannsteinerF3">3</a>)</div></li><li class="half_rhythm"><div>Hypertrichosis cubiti ("hairy elbows"), hypertrichosis of the back, and/or hypertrichosis of the lower limbs</div></li><li class="half_rhythm"><div>Sacral dimple</div></li><li class="half_rhythm"><div>Developmental delay / intellectual disability</div></li><li class="half_rhythm"><div>Hypotonia</div></li><li class="half_rhythm"><div>Feeding difficulties</div></li><li class="half_rhythm"><div>Failure to thrive</div></li><li class="half_rhythm"><div>Short stature</div></li><li class="half_rhythm"><div>Constipation</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figwiedemannsteinerF1" co-legend-rid="figlgndwiedemannsteinerF1"><a href="/books/NBK580718/figure/wiedemann-steiner.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figwiedemannsteinerF1" rid-ob="figobwiedemannsteinerF1"><img class="small-thumb" src="/books/NBK580718/bin/wiedemann-steiner-Image001.gif" src-large="/books/NBK580718/bin/wiedemann-steiner-Image001.jpg" alt="Figure 1. . Individuals with characteristic facial features of Wiedemann-Steiner syndrome; first 15 are shown in front and side views." /></a><div class="icnblk_cntnt" id="figlgndwiedemannsteinerF1"><h4 id="wiedemann-steiner.F1"><a href="/books/NBK580718/figure/wiedemann-steiner.F1/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Individuals with characteristic facial features of Wiedemann-Steiner syndrome; first 15 are shown in front and side views. Modified from Sheppard et al [2021]</p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figwiedemannsteinerF2" co-legend-rid="figlgndwiedemannsteinerF2"><a href="/books/NBK580718/figure/wiedemann-steiner.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figwiedemannsteinerF2" rid-ob="figobwiedemannsteinerF2"><img class="small-thumb" src="/books/NBK580718/bin/wiedemann-steiner-Image002.gif" src-large="/books/NBK580718/bin/wiedemann-steiner-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndwiedemannsteinerF2"><h4 id="wiedemann-steiner.F2"><a href="/books/NBK580718/figure/wiedemann-steiner.F2/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Individuals with characteristic facial features of Wiedemann-Steiner syndrome: family groups A. 3 sibs shown in front and side views</p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figwiedemannsteinerF3" co-legend-rid="figlgndwiedemannsteinerF3"><a href="/books/NBK580718/figure/wiedemann-steiner.F3/?report=objectonly" target="object" title="Figure 3. " class="img_link icnblk_img figpopup" rid-figpopup="figwiedemannsteinerF3" rid-ob="figobwiedemannsteinerF3"><img class="small-thumb" src="/books/NBK580718/bin/wiedemann-steiner-Image003.gif" src-large="/books/NBK580718/bin/wiedemann-steiner-Image003.jpg" alt="Figure 3. " /></a><div class="icnblk_cntnt" id="figlgndwiedemannsteinerF3"><h4 id="wiedemann-steiner.F3"><a href="/books/NBK580718/figure/wiedemann-steiner.F3/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerF3">Figure 3. </a></h4><p class="float-caption no_bottom_margin">Eight individuals with Wiedemann-Steiner syndrome shown as they age Modified from Sheppard et al [2021]</p></div></div><p>
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<b>Imaging findings</b>
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</p><ul><li class="half_rhythm"><div>Abnormal brain MRI, most commonly demonstrating abnormalities of the corpus callosum or abnormal myelination</div></li><li class="half_rhythm"><div>Congenital heart disease</div></li><li class="half_rhythm"><div>Genitourinary anomalies, most commonly vesiculouretal reflux with hydronephrosis, cryptorchidism in males, or absent uterus in females</div></li><li class="half_rhythm"><div>Vertebral anomalies, especially fusion anomalies in the cervical spine</div></li></ul><p><b>Family history.</b> Because WSS is typically caused by a <a class="def" href="/books/n/gene/glossary/def-item/de-novo/"><i>de novo</i></a> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, most probands represent a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case (i.e., a single occurrence in a family). Rarely, the family history may be consistent with <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> inheritance (e.g., affected males and females in multiple generations).</p></div><div id="wiedemann-steiner.Establishing_the_Diagn"><h3>Establishing the Diagnosis</h3><p>The diagnosis of WSS <b>is established</b> in a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> with <a href="#wiedemann-steiner.Suggestive_Findings">suggestive findings</a> and a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> pathogenic (or <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>) variant in <i>KMT2A</i> identified by <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (see <a href="/books/NBK580718/table/wiedemann-steiner.T.molecular_genetic_te/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerTmoleculargeneticte">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "<a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a> variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bk_pop" href="#wiedemann-steiner.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> <i>KMT2A</i> variant of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a> does not establish or rule out a diagnosis. (3) Because KMT2A is a <a class="def" href="/books/n/gene/glossary/def-item/histone/">histone</a> methyltransferase that regulates chromatin-mediated transcription (see <a href="#wiedemann-steiner.Molecular_Genetics">Molecular Genetics</a>), it has the ability to alter the <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> state of the genome; as such, assessment of the epigenetic signature may be considered to aid in the interpretation of the pathogenicity of a variant of uncertain clinical significance.</p><p>Molecular genetic testing approaches can include a combination of <b><a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted testing</b> (single-gene testing, <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a>) and <b>comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> (<a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>, <a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a>) depending on the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a>. Methylation studies, such as an <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> signature, can be considered in those individuals who have suggestive findings but in whom no <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>KMT2A</i> has been identified via <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> or genomic testing.</p><p>Gene-targeted testing requires that the clinician determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>(s) are likely involved, whereas comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing does not. Individuals with the distinctive findings described in <a href="#wiedemann-steiner.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#wiedemann-steiner.Option_1">Option 1</a>), whereas those with a <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> indistinguishable from many other inherited disorders with intellectual disability are more likely to be diagnosed using comprehensive genomic testing (see <a href="#wiedemann-steiner.Option_2">Option 2</a>).</p><div id="wiedemann-steiner.Option_1"><h4>Option 1</h4><p>When the phenotypic findings suggest the diagnosis of WSS, <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> approaches can include <b>single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing</b> or use of a <b><a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b>:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Single-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> testing.</b> Sequence analysis of <i>KMT2A</i> is performed first to detect small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants. Note: Depending on the sequencing method used, single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a>, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> to detect exon and whole-gene deletions or duplications.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>An autism / intellectual disability <a class="def" href="/books/n/gene/glossary/def-item/multigene-panel/">multigene panel</a></b> that includes <i>KMT2A</i> and other genes of interest (see <a href="#wiedemann-steiner.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></ul></div><div id="wiedemann-steiner.Option_2"><h4>Option 2</h4><p>When the <a class="def" href="/books/n/gene/glossary/def-item/phenotype/">phenotype</a> is indistinguishable from many other inherited disorders characterized by intellectual disability, comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing may be considered.</p><p><b>Comprehensive</b>
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<b><a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing</b> does not require the clinician to determine which <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> is likely involved. <b>Exome sequencing</b> is most commonly used; <b><a class="def" href="/books/n/gene/glossary/def-item/genome-sequencing/">genome sequencing</a></b> is also possible.</p><p>If testing for single-nucleotide pathogenic variants is normal but the suspicion for WSS remains high, <a class="def" href="/books/n/gene/glossary/def-item/methylation/">methylation</a> testing, including <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> signature, can be considered.</p><p>For an introduction to comprehensive <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> testing click <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div id="wiedemann-steiner.T.molecular_genetic_te" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Wiedemann-Steiner Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.molecular_genetic_te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.molecular_genetic_te_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.molecular_genetic_te_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_wiedemann-steiner.T.molecular_genetic_te_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>KMT2A</i>
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</td><td headers="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~99% <sup>4</sup></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> <sup>5</sup></td><td headers="hd_h_wiedemann-steiner.T.molecular_genetic_te_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><1% <sup>4</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="wiedemann-steiner.TF.1.1"><p class="no_margin">See <a href="/books/NBK580718/#wiedemann-steiner.molgen.TA">Table A. Genes and Databases</a> for <a class="def" href="/books/n/gene/glossary/def-item/chromosome/">chromosome</a> <a class="def" href="/books/n/gene/glossary/def-item/locus/">locus</a> and protein.</p></div></dd><dt>2. </dt><dd><div id="wiedemann-steiner.TF.1.2"><p class="no_margin">See <a href="#wiedemann-steiner.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>3. </dt><dd><div id="wiedemann-steiner.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, <a class="def" href="/books/n/gene/glossary/def-item/likely-benign/">likely benign</a>, of <a class="def" href="/books/n/gene/glossary/def-item/uncertain-significance/">uncertain significance</a>, <a class="def" href="/books/n/gene/glossary/def-item/likely-pathogenic/">likely pathogenic</a>, or pathogenic. Variants may include small intragenic deletions/insertions and <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a>, <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a>, and <a class="def" href="/books/n/gene/glossary/def-item/splice-site/">splice site</a> variants; typically, <a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> or whole-<a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> deletions/duplications are not detected. For issues to consider in interpretation of <a class="def" href="/books/n/gene/glossary/def-item/sequence-analysis/">sequence analysis</a> results, click <a href="/books/n/gene/app2/">here</a>.</p></div></dd><dt>4. </dt><dd><div id="wiedemann-steiner.TF.1.4"><p class="no_margin"><a class="bk_pop" href="#wiedemann-steiner.REF.chan.2019.9">Chan et al [2019]</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a></p></div></dd><dt>5. </dt><dd><div id="wiedemann-steiner.TF.1.5"><p class="no_margin">Gene-targeted <a class="def" href="/books/n/gene/glossary/def-item/deletion-duplication-analysis/">deletion/duplication analysis</a> detects intragenic deletions or duplications. Methods used may include a range of techniques such as <a class="def" href="/books/n/gene/glossary/def-item/quantitative-pcr/">quantitative PCR</a>, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a>-targeted microarray designed to detect single-<a class="def" href="/books/n/gene/glossary/def-item/exon/">exon</a> deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes may not be detected by these methods.</p></div></dd></dl></div></div></div></div></div></div><div id="wiedemann-steiner.Clinical_Characteristi"><h2 id="_wiedemann-steiner_Clinical_Characteristi_">Clinical Characteristics</h2><div id="wiedemann-steiner.Clinical_Description"><h3>Clinical Description</h3><p>Wiedemann-Steiner syndrome (WSS) is characterized by developmental delay, intellectual disability, and characteristic facial features, with or without additional <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies. To date, more than 200 individuals have been reported in the medical literature with a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> in <i>KMT2A</i> [<a class="bk_pop" href="#wiedemann-steiner.REF.jones.2012.358">Jones et al 2012</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.mendelsohn.2014.2079">Mendelsohn et al 2014</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.strom.2014.49">Strom et al 2014</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.bramswig.2015.553">Bramswig et al 2015</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.calvel.2015.289">Calvel et al 2015</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.steel.2015.755">Steel et al 2015</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.yuan.2015.636">Yuan et al 2015</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.miyake.2016.115">Miyake et al 2016</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.stellacci.2016.2389">Stellacci et al 2016</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.aggarwal.2017.285">Aggarwal et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.bogaert.2017.3702">Bogaert et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.enokizono.2017.2821">Enokizono et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.min_ko.2017.237">Min Ko et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sun.2017.510">Sun et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.lebrun.2018.107">Lebrun et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.li.2018.178">Li et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.stoyle.2018.18">Stoyle et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.chan.2019.9">Chan et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.chen.2019.5555">Chen et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.feldman.2019.300">Feldman et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.negri.2019.257">Negri et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.giangiobbe.2020.2877">Giangiobbe et al 2020</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.matis.2020.e3197">Matis et al 2020</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.mendoza.2020.e64">Mendoza 2020</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.demir.2021.46">Demir et al 2021</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.di_fede.2021.88">Di Fede et al 2021</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.nardello.2021.104133">Nardello et al 2021</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]. The following description of the phenotypic features associated with this condition is based on these reports.</p><div id="wiedemann-steiner.T.wiedemannsteiner_syn" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Wiedemann-Steiner Syndrome: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.wiedemannsteiner_syn/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.wiedemannsteiner_syn_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay /</b>
|
||
<br />
|
||
<b>Intellectual disability</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">97%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Characteristic <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~75%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most typically thick eyebrows, long eyelashes, widely spaced eyes, narrow & downslanted palpebral fissures</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypotonia</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~63%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constipation</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">50%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Failure to thrive</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">64%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Feeding difficulties</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">62%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Generally only in infancy & childhood</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT issues</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">63%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">About 60% of the cohort in <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a> had an ENT issue; issues also reported in other cohorts incl obstructive sleep apnea (18%), hearing loss (3%), & submucous cleft palate (3%).</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Hypertrichosis</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">44%-75%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most frequently of the face (thick eyebrows [73%] & long eyelashes [75%]), followed by the back (69%), elbows (58%), & lower limbs (44%)</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Short stature <sup>1</sup></b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~57%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Abnormal brain imaging</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~49%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly abnormal corpus callosum or abnormal myelination</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Dental anomalies <sup>2</sup></b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">57%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl advanced dental age w/premature loss of deciduous teeth & emergence of secondary teeth at atypical earlier age</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Sacral anomaly</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~45%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly sacral dimple, followed by tethered cord & spina bifida occulta</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Vertebral anomalies</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">46%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly fusion anomaly in cervical spine</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Abnormalities in genitourinary system</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~46.8%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Renal anomalies (29%); also uterine, testicular, & external genitalia anomalies</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neuropsychiatric differences</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">17%-38%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperactivity (38%), aggressive behavior (28%), & ASD (17%)</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Ophthalmologic abnormalities</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18%-32%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly strabismus, followed by astigmatism & blepharoptosis</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiac abnormalities</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">29%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most commonly patent ductus arteriosus & ventriculoseptal defects</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrinologic issues</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%-64%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl growth hormone deficiency (30%), premature adrenarche (27%), pituitary abnormality seen on brain MRI (64%), & abnormal bone age (63%)</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Seizures</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">18%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Incl focal, absence, & generalized</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immunologic issues</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">21%-54%</td><td headers="hd_h_wiedemann-steiner.T.wiedemannsteiner_syn_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abnormal immunoglobulin levels, insufficient response to pneumococcal vaccinations, recurrent infections (21%)</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASD = autism spectrum disorder; ENT = ears, nose, throat</p></div></dd><dt>1. </dt><dd><div id="wiedemann-steiner.TF.2.1"><p class="no_margin">Defined as length/height that is more than two standard deviations below the mean for age and sex or less than the fifth centile, or postnatal growth failure</p></div></dd><dt>2. </dt><dd><div id="wiedemann-steiner.TF.2.2"><p class="no_margin"><a class="bk_pop" href="#wiedemann-steiner.REF.aggarwal.2017.285">Aggarwal et al [2017]</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a></p></div></dd></dl></div></div></div><p><b>Characteristic <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> features.</b> Hypertrichosis cubiti, initially thought to be pathognomonic, is present in the majority of affected individuals [<a class="bk_pop" href="#wiedemann-steiner.REF.strom.2014.49">Strom et al 2014</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.aggarwal.2017.285">Aggarwal et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]. Characteristic facial features:</p><ul><li class="half_rhythm"><div>Thick eyebrows</div></li><li class="half_rhythm"><div>Long eyelashes</div></li><li class="half_rhythm"><div>Vertically narrow palpebral fissures</div></li><li class="half_rhythm"><div>Widely spaced eyes</div></li><li class="half_rhythm"><div>Wide nasal bridge with broad or bulbous tip</div></li><li class="half_rhythm"><div>Lateral (or other) flare to the eyebrow</div></li><li class="half_rhythm"><div>Downslanted palpebral fissures</div></li><li class="half_rhythm"><div>Blepharoptosis</div></li><li class="half_rhythm"><div>Exaggerated Cupid's bow</div></li><li class="half_rhythm"><div>Thin vermilion border to the upper lip</div></li><li class="half_rhythm"><div>Posteriorly rotated ears</div></li></ul><p><b>Developmental delay.</b> Most affected individuals have delayed developmental milestones, and some remain nonverbal and nonambulatory [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.li.2018.178">Li et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.chan.2019.9">Chan et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]. The median ages for developmental milestones:</p><ul><li class="half_rhythm"><div><b>Sitting.</b> Ten months (range 6-36 months)</div></li><li class="half_rhythm"><div><b>Standing.</b> 17 months (range 8-60 months)</div></li><li class="half_rhythm"><div><b>Walking.</b> 20 months (range 11-60 months)</div></li><li class="half_rhythm"><div><b>First words.</b> 18 months (range 8-60 months)</div></li></ul><p><b>Intellectual disability and educational achievement.</b> Most affected individuals require some degree of special education, but the majority of adults in one study completed high school.</p><ul><li class="half_rhythm"><div>Some affected individuals are able to maintain jobs as adults.</div></li><li class="half_rhythm"><div>IQ in those tested ranges from 40 to 85 (median 65).</div></li><li class="half_rhythm"><div>For more detailed information on developmental and learning issues, see <a class="bk_pop" href="#wiedemann-steiner.REF.feldman.2019.300">Feldman et al [2019]</a> and <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a>.</div></li></ul><p><b>Behavioral problems.</b> About 30% of affected individuals have aggressive behavior such as self-harm, though some also have physical aggression and tantrums. About 20% of affected individuals have autistic features suggestive of an autism spectrum diagnosis. Many children with WSS are described by their families as sweet and having a happy demeanor [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</p><p><b>Growth.</b> Most individuals have birth weights below the 25th centile.</p><ul><li class="half_rhythm"><div class="half_rhythm">Weight remains below the fifth centile for age in about one third of affected individuals.</div></li><li class="half_rhythm"><div class="half_rhythm">Almost 60% of affected individuals have short stature (defined as height <5th centile for age and sex OR 2 SD below the mean for age and sex OR "postnatal growth failure").</div><div class="half_rhythm">Bone age radiographs were abnormal (delayed, advanced, or disharmonic – i.e., different levels of maturation) in almost 65%.</div></li><li class="half_rhythm"><div class="half_rhythm">About one third of affected individuals have microcephaly (head circumference >5th centile for age OR 2 SD below the mean for age).</div></li></ul><p><b>Gastrointestinal.</b> About two thirds of affected individuals have a history of failure to thrive (FTT) and feeding difficulties, but fewer than one quarter require tube feeding. FTT can be transitory and nasogastric tube feedings can be temporarily useful. Constipation is present in about half of affected individuals and is more common in those with associated FTT.</p><p>
|
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<b>Neurologic</b>
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||
</p><ul><li class="half_rhythm"><div>Sacral anomaly, most commonly a sacral dimple, was seen in about 45% of affected individuals. Other sacral anomalies include spina bifida occulta and tethered cord requiring surgery.</div></li><li class="half_rhythm"><div>Hypotonia is present in about two thirds of affected individuals.</div><ul><li class="half_rhythm"><div>Hypotonia can be present at birth and may lead to recommendation for a gastrostomy tube or nasogastric tube.</div></li><li class="half_rhythm"><div>Some individuals continue to require supplemental nutrition through their gastrostomy tube.</div></li><li class="half_rhythm"><div>Hypotonia appears to improve over time in some.</div></li></ul></li><li class="half_rhythm"><div>Seizures are present in almost one fifth of affected individuals.</div><ul><li class="half_rhythm"><div>Seizure types include absence, partial complex epilepsy, eyelid myoclonia, tonic-clonic, febrile seizures, and infantile spasms [<a class="bk_pop" href="#wiedemann-steiner.REF.helbig.2016.898">Helbig et al 2016</a>].</div></li><li class="half_rhythm"><div>Epileptic encephalopathy has also been reported.</div></li><li class="half_rhythm"><div>Limited treatment information is available; however, multidrug resistance has been reported, and treatment with lamotrigine has been reported to be successful, although some affected individuals have not required treatment [<a class="bk_pop" href="#wiedemann-steiner.REF.koenig.2010.2372">Koenig et al 2010</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.stellacci.2016.2389">Stellacci et al 2016</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</div></li></ul></li><li class="half_rhythm"><div>Central apnea has also been reported.</div></li></ul><p><b>Brain MRI findings.</b> A structural brain abnormality is present in about half of affected individuals who have undergone brain imaging. Examples of findings [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]:</p><ul><li class="half_rhythm"><div>Abnormalities of the corpus callosum</div></li><li class="half_rhythm"><div>Abnormal myelination</div></li><li class="half_rhythm"><div>White matter changes, such as punctate foci of hyperintensity within the white matter, evidence of white matter volume loss, and paucity of white matter</div></li><li class="half_rhythm"><div>Chiari 1 malformation spectrum, which may include relatively narrow foramen magnum and platybasia</div></li><li class="half_rhythm"><div>Periventricular nodular heterotopia</div></li><li class="half_rhythm"><div>Choroid plexus cysts</div></li><li class="half_rhythm"><div>Abnormalities involving the pituitary gland, such as absent pituitary neurohypophysis, abnormal shape of the sella turcica, ectopic posterior bright spot with hypoplasia of hypothalamic pituitary axis, and pituitary hypoplasia (see <b>Endocrinologic</b> in this section)</div></li><li class="half_rhythm"><div>Cortical malformations, including bilateral frontal polymicrogyria [<a class="bk_pop" href="#wiedemann-steiner.REF.grangeia.2020.25">Grangeia et al 2020</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.nardello.2021.104133">Nardello et al 2021</a>]</div></li><li class="half_rhythm"><div>Hypoplastic optic nerves [<a class="bk_pop" href="#wiedemann-steiner.REF.chen.2019.5555">Chen et al 2019</a>]</div></li><li class="half_rhythm"><div>Cerebrospinal fluid anomalies including aqueductal stenosis and third ventricle dilatation [<a class="bk_pop" href="#wiedemann-steiner.REF.arora.2020.953">Arora et al 2020</a>]</div></li><li class="half_rhythm"><div>Cerebral atrophy</div></li><li class="half_rhythm"><div>Vermis hypoplasia [<a class="bk_pop" href="#wiedemann-steiner.REF.di_fede.2021.88">Di Fede et al 2021</a>]</div></li><li class="half_rhythm"><div>Cerebellar atrophy [<a class="bk_pop" href="#wiedemann-steiner.REF.giangiobbe.2020.2877">Giangiobbe et al 2020</a>]</div></li></ul><p><b>Integument/hair.</b> Hypertrichosis is common, occurring in approximately 50%-75% of affected individuals, and includes:</p><ul><li class="half_rhythm"><div>Eyebrows</div></li><li class="half_rhythm"><div>Long eyelashes</div></li><li class="half_rhythm"><div>Thick hair on the scalp</div></li><li class="half_rhythm"><div>Hypertrichosis of the back</div></li><li class="half_rhythm"><div>Hypertrichosis cubiti</div></li><li class="half_rhythm"><div>Hypertrichosis of the lower limbs</div></li></ul><p><b>Skeletal/limb.</b> Vertebral anomalies are the most common musculoskeletal finding, occurring in about half of affected individuals. Most of those who have vertebral anomalies have fusion in the cervical spine, most commonly at C2-C3, though some have abnormalities in the thoracic, lumbar, or sacral spine. Other skeletal anomalies include the following:</p><ul><li class="half_rhythm"><div class="half_rhythm">Rib anomalies (e.g., reduced number of rib pairs, hypoplastic appearance of ribs, cervical ribs) are found in about one third of affected individuals.</div></li><li class="half_rhythm"><div class="half_rhythm">Broad first digits and/or tapering fingers are present in about one quarter of affected individuals, with some individuals having persistent fetal fingertip pads [<a class="bk_pop" href="#wiedemann-steiner.REF.miyake.2016.115">Miyake et al 2016</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.enokizono.2017.2821">Enokizono et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.wang.2021.e1533">Wang et al 2021</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">Fewer than one fifth of affected individuals have scoliosis, which in rare cases can be severe enough to require surgery.</div></li><li class="half_rhythm"><div class="half_rhythm">Pectus excavatum has been described in a small number of affected individuals.</div></li><li class="half_rhythm"><div class="half_rhythm">Hip dysplasia has also been seen in a small number of affected individuals, although none of those with hip dysplasia were breech at birth.</div><div class="half_rhythm">Several individuals required surgery and one required a Pavlik harness.</div></li><li class="half_rhythm"><div class="half_rhythm">One individual had scaphocephaly and another had metopic craniosynostosis [<a class="bk_pop" href="#wiedemann-steiner.REF.nardello.2021.104133">Nardello et al 2021</a>]. The authors are also aware of a second individual with metopic craniosynostosis.</div></li></ul><p><b>Cardiac.</b> Cardiac abnormalities were present in about one third of those who underwent cardiac evaluation. Cardiac issues can include:</p><ul><li class="half_rhythm"><div>Structural cardiac anomalies (patent ductus arteriosus, patent foramen ovale, right aortic arch, aortic insufficiency, bicuspid aortic valve, atrial septal defect, ventricular septal defect, tetralogy of Fallot, aberrant right subclavian artery, mitral valve prolapse, dextrocardia, mitral regurgitation, tricuspid regurgitation, overriding aorta, and thickened aortic valve)</div></li><li class="half_rhythm"><div>Arrhythmia (one affected individual required a pacemaker), including third-degree AV block [<a class="bk_pop" href="#wiedemann-steiner.REF.bogaert.2017.3702">Bogaert et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.li.2018.178">Li et al 2018</a>]</div></li><li class="half_rhythm"><div>Pulmonary hypertension</div></li><li class="half_rhythm"><div>Syncopal episodes</div></li></ul><p><b>Genitourinary.</b> Abnormalities in the genitourinary system are present in almost half of affected individuals.</p><ul><li class="half_rhythm"><div>Renal anomaly was seen in about one quarter and included vesiculouretal reflux with hydronephrosis.</div></li><li class="half_rhythm"><div>Uterine or testicular anomalies were seen in almost 20%, including absent uterus in females and cryptorchidism in males.</div></li><li class="half_rhythm"><div>About 10% have an external genital anomaly, including prominent clitoris, underdeveloped scrotum, and hypospadias.</div></li></ul><p><b>Eyes.</b> A wide variety of ophthalmologic abnormalities are seen, including:</p><ul><li class="half_rhythm"><div>Strabismus</div></li><li class="half_rhythm"><div>Astigmatism</div></li><li class="half_rhythm"><div>Hyperopia</div></li><li class="half_rhythm"><div>Myopia</div></li><li class="half_rhythm"><div>Amblyopia</div></li><li class="half_rhythm"><div>Lacrimal duct abnormalities</div></li><li class="half_rhythm"><div>Ptosis</div></li><li class="half_rhythm"><div>Rarely, cataract, coloboma, or glaucoma</div></li></ul><p><b>ENT.</b> Obstructive sleep apnea is the most common finding, occurring in about one quarter of affected individuals and necessitating tonsillectomy and adenoidectomy in close to 20% of those who have obstructive sleep apnea.</p><p><b>Dental/oral.</b> More than half of affected individuals have a dental issue, the most common of which is advanced dental age characterized by premature loss of deciduous teeth and emergence of secondary teeth at an atypical earlier age. Other features include malocclusion, <a class="def" href="/books/n/gene/glossary/def-item/dysmorphic/">dysmorphic</a> teeth, hypodontia, supernumerary teeth, poor enamel, caries, high-arched palate needing a palate expander, and gum issues.</p><p><b>Endocrinologic.</b> Endocrine abnormalities include:</p><ul><li class="half_rhythm"><div>Short stature (see <b>Growth</b> in this section)</div></li><li class="half_rhythm"><div>Premature adrenarche</div></li><li class="half_rhythm"><div>Menorrhagia, polycystic ovary syndrome, and/or irregular menses</div></li><li class="half_rhythm"><div>Abnormality of the pituitary gland seen on brain MRI (see <b>Brain MRI findings</b> in this section)</div></li><li class="half_rhythm"><div>Growth hormone (GH) deficiency, defined by low serum GH, IGF-1 or GH stimulation test</div></li><li class="half_rhythm"><div>Osteopenia</div></li><li class="half_rhythm"><div>Hypothyroidism (including <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> hypothyroidism and Hashimoto thyroiditis)</div></li><li class="half_rhythm"><div>Hypoparathyroidism</div></li></ul><p><b>Immunologic</b> issues have also been reported, including [<a class="bk_pop" href="#wiedemann-steiner.REF.jones.2012.358">Jones et al 2012</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.stellacci.2016.2389">Stellacci et al 2016</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.bogaert.2017.3702">Bogaert et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]:</p><ul><li class="half_rhythm"><div>Immunodeficiency, including common variable immunodeficiency</div></li><li class="half_rhythm"><div>Insufficient response to vaccinations</div></li><li class="half_rhythm"><div>History of recurrent infections</div></li><li class="half_rhythm"><div>Recurrent fevers of unknown origin</div></li><li class="half_rhythm"><div>Eosinophilia [<a class="bk_pop" href="#wiedemann-steiner.REF.zhang.2019.38">Zhang et al 2019</a>]</div></li></ul><p>One boy had recurrent pulmonary infections and died of sepsis [<a class="bk_pop" href="#wiedemann-steiner.REF.bramswig.2015.553">Bramswig et al 2015</a>].</p><p><b>Prognosis.</b> It is unknown whether life span in WSS is abnormal. Multiple adults have been reported in the literature [<a class="bk_pop" href="#wiedemann-steiner.REF.li.2018.178">Li et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.feldman.2019.300">Feldman et al 2019</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]. While some adults do not work, one attended a daytime rehabilitation program, another owned a construction business, and another was currently in college managing without academic assistance. Adults with WSS could have affected children. Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.</p></div><div id="wiedemann-steiner.GenotypePhenotype_Corr"><h3>Genotype-Phenotype Correlations</h3><p>Some <a class="def" href="/books/n/gene/glossary/def-item/genotype-phenotype-correlations/">genotype-phenotype correlations</a> have been established.</p><ul><li class="half_rhythm"><div>Individuals with <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> variants in <i>KMT2A</i> are more likely to have hypotonia than those with non-loss-of-function variants [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</div></li><li class="half_rhythm"><div>In contrast, participants with non-<a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> variants are more likely to have seizures [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</div></li><li class="half_rhythm"><div>Missense variants in the CXXC DNA-binding <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> (amino acids 1147-1195) may be associated with more significant neurodevelopmental issues [<a class="bk_pop" href="#wiedemann-steiner.REF.min_ko.2017.237">Min Ko et al 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.li.2018.178">Li et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.lebrun.2018.107">Lebrun et al 2018</a>].</div></li></ul></div><div id="wiedemann-steiner.Nomenclature"><h3>Nomenclature</h3><p>In 1970, Dr P Beighton described a father and two of his children with <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> hypertrichosis cubiti or "hairy elbows" syndrome [<a class="bk_pop" href="#wiedemann-steiner.REF.beighton.1970.158">Beighton 1970</a>]. Subsequently, Dr HR Wiedemann and colleagues described a male with growth deficiency, developmental delay, strabismus, renal calyceal dilatation, and characteristic facial features [<a class="bk_pop" href="#wiedemann-steiner.REF.wiedemann.1989">Wiedemann et al 1989</a>]. In 2000, Dr CE Steiner and Dr AP Marques reported a female with features similar to those reported by Beighton and Wiedemann and suggested a common diagnosis [<a class="bk_pop" href="#wiedemann-steiner.REF.steiner.2000.155">Steiner & Marques 2000</a>]. Although "hairy elbows syndrome" has been used to describe WSS in some articles, "Wiedemann-Steiner syndrome" is now commonly used. Alternatively, <i>KMT2A</i>-related neurodevelopmental disorder can be used, following the naming system proposed by <a class="bk_pop" href="#wiedemann-steiner.REF.biesecker.2021.8">Biesecker et al [2021]</a>.</p></div><div id="wiedemann-steiner.Prevalence"><h3>Prevalence</h3><p>The prevalence of WSS is not known. Almost 250 individuals have been reported in the literature. Multiple adults were diagnosed as part of their child's evaluation, so it is possible that WSS could be underdiagnosed [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</p></div></div><div id="wiedemann-steiner.Genetically_Related_Al"><h2 id="_wiedemann-steiner_Genetically_Related_Al_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> pathogenic variants in <i>KMT2A</i>.</p><p><b>Sporadic tumors</b> (including acute leukemia, thymomas, and breast cancer) occurring as single tumors in the absence of any other findings of Wiedemann-Steiner syndrome frequently harbor a <a class="def" href="/books/n/gene/glossary/def-item/somatic-pathogenic-variant/">somatic pathogenic variant</a> in (or a <a class="def" href="/books/n/gene/glossary/def-item/genomic/">genomic</a> rearrangement that includes) <i>KMT2A</i> that is <b>not</b> present in the <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a>. In these circumstances predisposition to these tumors is not heritable. For more information, see <a href="#wiedemann-steiner.Cancer_and_Benign_Tumo">Cancer and Benign Tumors</a>.</p></div><div id="wiedemann-steiner.Differential_Diagnosis"><h2 id="_wiedemann-steiner_Differential_Diagnosis_">Differential Diagnosis</h2><p>The features associated with Wiedemann-Steiner syndrome (WSS) overlap those of a wide range of disorders. <a href="/books/NBK580718/table/wiedemann-steiner.T.key_disorders_in_the/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerTkeydisordersinthe">Table 3</a> summarizes those disorders most commonly considered in individuals with clinical findings consistent with WSS. For less commonly considered disorders in the differential diagnosis, refer to <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a>.</p><div id="wiedemann-steiner.T.key_disorders_in_the" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Key Disorders in the Differential Diagnosis of Wiedemann-Steiner Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.key_disorders_in_the/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.key_disorders_in_the_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Clinical Features of DiffDx Disorder</th></tr><tr><th headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4" id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Overlapping w/WSS</th><th headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4" id="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distinguishing from WSS</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ARID1A</i>
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<br />
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<i>ARID1B</i>
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<br />
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<i>ARID2</i>
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<br />
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<i>DPF2</i>
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<br />
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<i>SMARCA4</i>
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<br />
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<i>SMARCB1</i>
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<br />
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<i>SMARCC2</i>
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<br />
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<i>SMARCE1</i>
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<br />
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<i>SOX4</i>
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<br />
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<i>SOX11</i>
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</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/coffin-siris/">Coffin-Siris syndrome</a>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Syndromic short stature, hypertrichosis w/long eyelashes & prominent eyebrows</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Distal digit hypoplasia (usually 5th digit)</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>BRAF</i>
|
||
<br />
|
||
<i>KRAS</i>
|
||
<br />
|
||
<i>LZTR1</i>
|
||
<br />
|
||
<i>MAP2K1</i>
|
||
<br />
|
||
<i>NRAS</i>
|
||
<br />
|
||
<i>PTPN11</i>
|
||
<br />
|
||
<i>RAF1</i>
|
||
<br />
|
||
<i>RIT1</i>
|
||
<br />
|
||
<i>SOS1</i>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/noonan/">Noonan syndrome</a>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />AR <sup>1</sup></td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature, structural heart abnormalities, pulmonary hypertension, ocular abnormalities, & hypotonia</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Higher frequency of <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart defects (50%-80%), pulmonary valve stenosis, & absence of hypertrichosis</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>BRD4</i>
|
||
<br />
|
||
<i>HDAC8</i>
|
||
<br />
|
||
<i>NIPBL</i>
|
||
<br />
|
||
<i>RAD21</i>
|
||
<br />
|
||
<i>SMC1A</i>
|
||
<br />
|
||
<i>SMC3</i>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/cdls/">Cornelia de Lange syndrome</a>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />XL <sup>2</sup></td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertrichosis, short stature, growth failure, DD/ID, ophthalmologic abnormalities, & recurrent infections</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Limb involvement, upper-extremity deficiencies ranging from severe reduction defects w/complete absence of forearms to various forms of oligodactyly</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>CREBBP</i>
|
||
<br />
|
||
<i>EP300</i>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/rsts/">Rubinstein-Taybi Syndrome</a>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Short stature, DD/ID, hypertrichosis, <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart disease</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperinsulinism, grimacing/typical smile</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>KDM6A</i>
|
||
<br />
|
||
<i>KMT2D</i>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<a href="/books/n/gene/kabuki/">Kabuki syndrome</a>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD<br />XL <sup>3</sup></td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hypertrichosis, short stature, growth deficiency, DD/ID, multiple <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> anomalies</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hyperinsulinism</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<i>TASP1</i>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Suleiman-El-Hattab syndrome (OMIM <a href="https://omim.org/entry/618950" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">618950</a>)</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DD, hypotonia, microcephaly, feeding difficulties w/FTT, recurrent respiratory infections, cardiovascular malformations, happy demeanor, & distinctive facial features <sup>4</sup></td><td headers="hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_1_4 hd_h_wiedemann-steiner.T.key_disorders_in_the_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Prominent glabella</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>; DD = developmental delay; DiffDx = differential diagnosis; FTT = failure to thrive; ID = intellectual disability, MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; WSS = Wiedemann-Steiner syndrome; XL = <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a></p></div></dd><dt>1. </dt><dd><div id="wiedemann-steiner.TF.3.1"><p class="no_margin">Noonan syndrome (NS) is most often inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner. <i>LZTR1</i>-related NS can be inherited in either an autosomal dominant or an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-recessive/">autosomal recessive</a> manner.</p></div></dd><dt>2. </dt><dd><div id="wiedemann-steiner.TF.3.2"><p class="no_margin"><i>NIPBL</i>-related Cornelia de Lange syndrome (CdLS), <i>RAD21</i>-related CdLS, <i>SMC3</i>-related CdLS, and <i>BRD4</i>-related CdLS are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner; <i>HDAC8</i>-related CdLS and <i>SMC1A</i>-related CdLS are inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner.</p></div></dd><dt>3. </dt><dd><div id="wiedemann-steiner.TF.3.3"><p class="no_margin"><i>KMT2D</i>-related Kabuki syndrome (KS) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner; <i>KDM6A</i>-related KS is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/x-linked/">X-linked</a> manner.</p></div></dd><dt>4. </dt><dd><div id="wiedemann-steiner.TF.3.4"><p class="no_margin"><i>TASP1</i> cleaves <i>KMT2A</i>, which may account for the similarity between WSS and Suleiman-El-Hattab syndrome [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</p></div></dd></dl></div></div></div></div><div id="wiedemann-steiner.Management"><h2 id="_wiedemann-steiner_Management_">Management</h2><p>Suggested clinical practice guidelines for Wiedemann-Steiner syndrome (WSS) have been published. See <a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al [2018]</a> (<a href="https://onlinelibrary.wiley.com/doi/10.1111/cge.13254" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>), <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a> (<a href="https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.62124" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>). Note: Institutional access or purchase required.</p><div id="wiedemann-steiner.Evaluations_Following"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with WSS, the evaluations summarized in <a href="/books/NBK580718/table/wiedemann-steiner.T.recommended_evaluati/?report=objectonly" target="object" rid-ob="figobwiedemannsteinerTrecommendedevaluati">Table 4</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div id="wiedemann-steiner.T.recommended_evaluati" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Wiedemann-Steiner Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.recommended_evaluati/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.recommended_evaluati_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Constitutional</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Measurement of growth parameters</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To identify those w/poor growth, incl those who have FTT & those who may have growth hormone deficiency</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl brain MRI, as clinically indicated</div></li><li class="half_rhythm"><div>Consider EEG if seizures are a concern & in those who have a <a class="def" href="/books/n/gene/glossary/def-item/loss-of-function/">loss-of-function</a> pathogenic <i>KMT2A</i> variant.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech-language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Psychiatric/</b>
|
||
<br />
|
||
<b>Behavioral</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persons age >12 mos: screen for behavior concerns incl sleep disturbances, aggressive behaviors, &/or traits suggestive of ASD.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider spinal radiographs, vertebral computed tomography or tonodensometry.</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform mgmt</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Orthopedics / physical medicine & rehab / PT & OT eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To incl assessment of:
|
||
<ul><li class="half_rhythm"><div>Gross motor & fine motor skills</div></li><li class="half_rhythm"><div>Signs/symptoms suggestive of vertebral anomalies & hip dysplasia</div></li><li class="half_rhythm"><div>Mobility, ADL, & need for adaptive devices</div></li><li class="half_rhythm"><div>Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal/</b>
|
||
<br />
|
||
<b>Feeding</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gastroenterology / nutrition / feeding team eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl eval of nutritional status</div></li><li class="half_rhythm"><div>Consider eval for gastrostomy tube placement in those w/FTT.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Evaluate for signs/symptoms of constipation.</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmologic eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For diagnosis & treatment of strabismus, blepharoptosis, refractive disorders, & other rare eye complications</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT/Mouth</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider sleep study.</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess for sleep apnea</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Pediatric dentistry eval in those age >1 yr</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate early loss of deciduous teeth & emergence of secondary dentition</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Echocardiogram & EKG</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To evaluate for <a class="def" href="/books/n/gene/glossary/def-item/congenital/">congenital</a> heart defects & to screen for arrhythmia</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genitourinary</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To assess for renal & bladder abnormalities</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Consider external pelvic ultrasound in female neonates or in females of pubertal age or older. <sup>1</sup></td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To screen for uterine anomalies</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Integument</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dermatologic eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">If desired by family to assist in mgmt of hypertrichosis</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Endocrinology eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess for short stature, growth hormone deficiency, hypothyroidism, & metabolic bone disease</div></li><li class="half_rhythm"><div>May consist of blood tests as well as radiographs (e.g., bone age x-rays) depending on clinical context</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immunologic</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Immunologic eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess for immunodeficiency & vaccine response</div></li><li class="half_rhythm"><div>May incl quantitative immunoglobulins, vaccine titers, lymphocyte profile</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Genetic</b>
|
||
<br />
|
||
<b>counseling</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>2</sup></td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of WSS to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family support</b>
|
||
<br />
|
||
<b>& resources</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_wiedemann-steiner.T.recommended_evaluati_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
||
<ul><li class="half_rhythm"><div>Community or <a href="#wiedemann-steiner.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>; <sup>3</sup></div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ADL = activities of daily living; ASD = autism spectrum disorder; EEG = electroencephalogram; EKG = electrocardiogram; FTT = failure to thrive; MOI = <a class="def" href="/books/n/gene/glossary/def-item/mode-of-inheritance/">mode of inheritance</a>; MRI = magnetic resonance imaging; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="wiedemann-steiner.TF.4.1"><p class="no_margin">Pelvic ultrasound and even pelvic MRI in females who have not experienced recent estrogen may not be able to identify a uterus. Neither of these imaging modalities is sufficient in this scenario to confirm absence of a uterus. Referral to a gynecologist for evaluation could be considered.</p></div></dd><dt>2. </dt><dd><div id="wiedemann-steiner.TF.4.2"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd><dt>3. </dt><dd><div id="wiedemann-steiner.TF.4.3"><p class="no_margin">WSS parent-specific resources may include the WSS Foundation (see <a href="#wiedemann-steiner.Resources">Resources</a>) or the WSS Facebook group.</p></div></dd></dl></div></div></div></div><div id="wiedemann-steiner.Treatment_of_Manifesta"><h3>Treatment of Manifestations</h3><div id="wiedemann-steiner.T.treatment_of_manifes" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Wiedemann-Steiner Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.treatment_of_manifes/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.treatment_of_manifes_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Epilepsy</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist or epileptologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.</div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>1</sup></div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Developmental delay /</b>
|
||
<br />
|
||
<b>Intellectual disability /</b>
|
||
<br />
|
||
<b>Behavioral issues</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#wiedemann-steiner.Developmental_Delay__I">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Congenital hip dysplasia</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per orthopedist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May incl use of Pavlik harness, & in extreme cases may require surgical intervention</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Fusion of cervical vertebrae</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Individual assessment per orthopedist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rarely, affected persons have required laminectomy.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Poor weight gain /</b>
|
||
<br />
|
||
<b>Failure to thrive</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Feeding therapy</div></li><li class="half_rhythm"><div>Nasogastric or gastrostomy tube placement may be required for persistent feeding issues.</div></li></ul>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Low threshold for clinical feeding eval</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Bowel dysfunction</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Stool softeners, prokinetics, osmotic agents, or laxatives as needed</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Strabismus, astigmatism, & other</b>
|
||
<br />
|
||
<b>refractive errors</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment by ophthalmologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Blepharoptosis</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consideration of oculoplastic surgery</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Obstructive sleep apnea</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment may incl CPAP, BiPAP, or surgical removal of tonsils & adenoids.</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Congenital heart</b>
|
||
<br />
|
||
<b>defects & arrhythmias</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per cardiologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May incl medical mgmt w/antiarrhythmic or surgical mgmt</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Renal anomalies</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per nephrologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Uterine anomalies</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per gynecologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth hormone deficiency</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Growth hormone therapy</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">This treatment is typically undertaken by an endocrinologist.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Thyroid dysfunction</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Thyroid hormone replacement therapy</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Metabolic bone disease</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard treatment per endocrinologist</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">May incl vitamin D supplementation</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Frequent infections /</b>
|
||
<br />
|
||
<b>Immune dysfunction</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Consider IVIG in those w/low antibody levels &/or prophylactic antibiotic in those w/frequent infections.</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mgmt by immunologist is recommended.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/Community</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ensure appropriate social work involvement to connect families w/local resources, respite, & support.</div></li><li class="half_rhythm"><div>Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.</div></li></ul>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.treatment_of_manifes_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Ongoing assessment of need for palliative care involvement &/or home nursing</div></li><li class="half_rhythm"><div>Consider involvement in adaptive sports or Special Olympics.</div></li></ul>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">ASM = anti-seizure medication; BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; IVIG = intravenous immunoglobulin; OT = occupational therapy; PT = physical therapy</p></div></dd><dt>1. </dt><dd><div id="wiedemann-steiner.TF.5.1"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></div></div></div><div id="wiedemann-steiner.Developmental_Delay__I"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="wiedemann-steiner.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p>
|
||
<b>Gross motor dysfunction</b>
|
||
</p><ul><li class="half_rhythm"><div>Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., scoliosis, hip dislocation) [<a class="bk_pop" href="#wiedemann-steiner.REF.mendoza.2020.e64">Mendoza 2020</a>].</div></li><li class="half_rhythm"><div>Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</div></li></ul><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction</b> should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.</p></div><div id="wiedemann-steiner.SocialBehavioral_Conce"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="wiedemann-steiner.Surveillance"><h3>Surveillance</h3><div id="wiedemann-steiner.T.recommended_surveill" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Wiedemann-Steiner Syndrome</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.T.recommended_surveill/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.T.recommended_surveill_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Growth/Feeding</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Measure growth parameters & evaluate growth velocity.</div></li><li class="half_rhythm"><div>Evaluate nutritional status.</div></li></ul>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_3" rowspan="10" colspan="1" style="text-align:left;vertical-align:middle;">At each visit <sup>2</sup></td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Gastrointestinal</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for constipation.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Neurologic</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Monitor those w/seizures as clinically indicated. <sup>1</sup></div></li><li class="half_rhythm"><div>Assess for new manifestations such as seizures.</div></li><li class="half_rhythm"><div>Assess for clinical signs of medullar compression, esp in those w/vertebral anomalies.</div></li></ul>
|
||
</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Development</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Psychiatric/</b>
|
||
<br />
|
||
<b>Behavioral</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Behavior assessment for attention & aggressive behaviors</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Musculoskeletal</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Physical medicine, OT/PT assessment of mobility, self-help skills</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Cardiovascular</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for any signs/symptoms of arrhythmia.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Immunologic</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for any signs of frequent infection.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Family/</b>
|
||
<br />
|
||
<b>Community</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>ENT/Mouth</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for signs/symptoms of sleep disturbance.</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Dental eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">After eruption of primary teeth, every 6 mos</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Endocrine</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assessment for premature thelarche or pubertal abnormalities (primary amenorrhea)</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Starting in childhood until growth/menarche is complete</td></tr><tr><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
||
<b>Eyes</b>
|
||
</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology eval</td><td headers="hd_h_wiedemann-steiner.T.recommended_surveill_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually or as clinically indicated</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt>1. </dt><dd><div id="wiedemann-steiner.TF.6.1"><p class="no_margin">May include EEG follow up, as indicated</p></div></dd><dt>2. </dt><dd><div id="wiedemann-steiner.TF.6.2"><p class="no_margin">Visit frequency may vary based on individual needs, but generally visits may be every six months in early childhood and transition to annual visits around school age.</p></div></dd></dl></div></div></div></div><div id="wiedemann-steiner.AgentsCircumstances_to"><h3>Agents/Circumstances to Avoid</h3><p>The authors are aware of one individual with WSS who developed hyperammonemia with the use of the anti-seizure medication valproate. While this is not specific to individuals with WSS, valproate should be used with caution.</p></div><div id="wiedemann-steiner.Evaluation_of_Relative"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#wiedemann-steiner.Related_Genetic_Counse">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="wiedemann-steiner.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Some women with WSS have a seizure disorder that is treated with an anti-seizure medication. In general, women with epilepsy or a seizure disorder of any cause are at greater risk for mortality during pregnancy than pregnant women without a seizure disorder; use of anti-seizure medication during pregnancy reduces this risk. However, exposure to anti-seizure medication may increase the risk for adverse fetal outcome (depending on the drug used, the dose, and the stage of pregnancy at which the medication is taken). Nevertheless, the risk of an adverse outcome to the fetus from anti-seizure medication exposure is often less than that associated with exposure to an untreated maternal seizure disorder. Therefore, use of anti-seizure medication to treat a maternal seizure disorder during pregnancy is typically recommended. Discussion of the risks and benefits of using a given anti-seizure medication during pregnancy should ideally take place prior to conception. Transitioning to a lower-risk medication prior to pregnancy may be possible [<a class="bk_pop" href="#wiedemann-steiner.REF.sarma.2016.467">Sarma et al 2016</a>].</p><p>Cervical spine anomalies may lead to immobility or instability, which may complicate airway management. Vertebral anomalies or scoliosis in the thoracic or lumbar spine may complicate spinal or epidural anesthesia.</p><p>Affected fetuses may be at risk for late prematurity, with average gestation ranging from 36 to 38 weeks [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>].</p><p>See <a href="https://www.mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for further information on medication use during pregnancy.</p></div><div id="wiedemann-steiner.Therapies_Under_Invest"><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="wiedemann-steiner.Genetic_Counseling"><h2 id="_wiedemann-steiner_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="wiedemann-steiner.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Wiedemann-Steiner syndrome (WSS) is inherited in an <a class="def" href="/books/n/gene/glossary/def-item/autosomal-dominant/">autosomal dominant</a> manner.</p></div><div id="wiedemann-steiner.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
||
<b>Parents of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a></b>
|
||
</p><ul><li class="half_rhythm"><div class="half_rhythm">Most individuals diagnosed with WSS whose parents have undergone <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> have the disorder as 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 class="half_rhythm">Rarely, individuals diagnosed with WSS have an affected parent [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">If the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> appears to be the only affected family member (i.e., a <a class="def" href="/books/n/gene/glossary/def-item/simplex/">simplex</a> case), <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> is recommended for the parents of the proband to confirm their genetic status and to allow reliable <a class="def" href="/books/n/gene/glossary/def-item/recurrence-risk/">recurrence risk</a> counseling.</div></li><li class="half_rhythm"><div class="half_rhythm">If the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in the <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> is not identified in either apparently asymptomatic parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> has 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>The <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> inherited a <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> from a parent with <a class="def" href="/books/n/gene/glossary/def-item/germline/">germline</a> (or somatic and germline) <a class="def" href="/books/n/gene/glossary/def-item/mosaicism/">mosaicism</a>.* Note: Testing of parental leukocyte DNA may not detect all instances of <a class="def" href="/books/n/gene/glossary/def-item/somatic-mosaicism/">somatic mosaicism</a> and will not detect a pathogenic variant that is present in the germ cells only.</div></li></ul><div class="half_rhythm">* A parent with somatic and <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> for a <i>KMT2A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> may be mildly/minimally affected [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">The family history of some individuals diagnosed with WSS may appear to be negative because of failure to recognize the disorder in mildly affected family members. Therefore, an apparently negative family history cannot be confirmed without appropriate clinical evaluation of the parents and/or <a class="def" href="/books/n/gene/glossary/def-item/molecular-genetic-testing/">molecular genetic testing</a> (to establish that neither parent is <a class="def" href="/books/n/gene/glossary/def-item/heterozygous/">heterozygous</a> for the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> identified in 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 the sibs of the proband depends on the clinical/genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the <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 is 50%.</div></li><li class="half_rhythm"><div>Clinical variability among affected sibs with the same <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been observed. In a family with six sibs with WSS, all had failure to thrive and feeding difficulties, there was a range of developmental delay, and some had structural malformations whereas others did not [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</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 <i>KMT2A</i> <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 slightly greater than that of the general population because of the possibility of <a class="def" href="/books/n/gene/glossary/def-item/germline-mosaicism/">germline mosaicism</a> in a clinically unaffected parent. Mosaicism for a <i>KMT2A</i> pathogenic variant in a clinically unaffected parent has been described in one family [<a class="bk_pop" href="#wiedemann-steiner.REF.baer.2018.141">Baer et al 2018</a>].</div></li><li class="half_rhythm"><div>If the parents are clinically unaffected after a thorough evaluation for subtle findings but their genetic status is unknown, the risk to the sibs of a <a class="def" href="/books/n/gene/glossary/def-item/proband/">proband</a> appears to be low but increased over that of the general population because of the 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 WSS has a 50% chance of inheriting the <i>KMT2A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>.</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 has the <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a>, members of the parent's family may be at risk.</p></div><div id="wiedemann-steiner.Related_Genetic_Counse"><h3>Related Genetic Counseling Issues</h3><p>
|
||
<b>Family planning</b>
|
||
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/<a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer <a class="def" href="/books/n/gene/glossary/def-item/genetic-counseling/">genetic counseling</a> (including discussion of potential risks to offspring and reproductive options) to young adults who are affected.</div></li></ul></div><div id="wiedemann-steiner.Prenatal_Testing_and_P"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>KMT2A</i> <a class="def" href="/books/n/gene/glossary/def-item/pathogenic-variant/">pathogenic variant</a> has been identified in an affected family member, prenatal and <a class="def" href="/books/n/gene/glossary/def-item/preimplantation-genetic-testing/">preimplantation genetic testing</a> are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of <a class="def" href="/books/n/gene/glossary/def-item/prenatal-testing/">prenatal testing</a>. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="wiedemann-steiner.Resources"><h2 id="_wiedemann-steiner_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>Wiedemann-Steiner Syndrome Foundation</b>
|
||
</div><div>1314 44th Street</div><div>Sacramento 95819</div><div><b>Phone:</b> 916-502-2120</div><div><b>Email:</b> info@wssfoundation.org</div><div>
|
||
<a href="https://www.wssfoundation.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.wssfoundation.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>American Association on Intellectual and Developmental Disabilities (AAIDD)</b>
|
||
</div><div><b>Phone:</b> 202-387-1968</div><div>
|
||
<a href="https://www.aaidd.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aaidd.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>Face Equality International</b>
|
||
</div><div>United Kingdom</div><div>
|
||
<a href="https://faceequalityinternational.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">faceequalityinternational.org</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>MedlinePlus</b>
|
||
</div><div>
|
||
<a href="http://www.nlm.nih.gov/medlineplus/ency/article/001523.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Intellectual Disability</a>
|
||
</div></li><li class="half_rhythm"><div>
|
||
<b>CoRDS Registry</b>
|
||
</div><div>Sanford Research</div><div><b>Phone:</b> 605-312-6300</div><div>
|
||
<a href="https://research.sanfordhealth.org/rare-disease-registry" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CoRDS Registry</a>
|
||
</div></li></ul>
|
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</div><div id="wiedemann-steiner.Molecular_Genetics"><h2 id="_wiedemann-steiner_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="wiedemann-steiner.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Wiedemann-Steiner Syndrome: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK580718/table/wiedemann-steiner.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_wiedemann-steiner.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_wiedemann-steiner.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="/gene/4297" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
||
<i>KMT2A</i>
|
||
</a>
|
||
</td><td headers="hd_b_wiedemann-steiner.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=4297" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">11q23<wbr style="display:inline-block"></wbr>.3</a>
|
||
</td><td headers="hd_b_wiedemann-steiner.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://www.uniprot.org/uniprot/Q03164" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Histone-lysine N-methyltransferase 2A</a>
|
||
</td><td headers="hd_b_wiedemann-steiner.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="http://databases.lovd.nl/shared/genes/KMT2A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KMT2A database</a>
|
||
</td><td headers="hd_b_wiedemann-steiner.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=KMT2A" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KMT2A</a>
|
||
</td><td headers="hd_b_wiedemann-steiner.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
||
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=KMT2A[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KMT2A</a>
|
||
</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div id="wiedemann-steiner.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="wiedemann-steiner.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Wiedemann-Steiner Syndrome (<a href="/omim/159555,605130" 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/NBK580718/table/wiedemann-steiner.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__wiedemann-steiner.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/159555" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">159555</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LYSINE-SPECIFIC METHYLTRANSFERASE 2A; KMT2A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
||
<a href="/omim/605130" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605130</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">WIEDEMANN-STEINER SYNDROME; WDSTS</td></tr></tbody></table></div></div><div id="wiedemann-steiner.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The <i>KMT2A</i> <a class="def" href="/books/n/gene/glossary/def-item/gene-product/">gene product</a> is a DNA-binding protein that methylates <a class="def" href="/books/n/gene/glossary/def-item/histone/">histone</a> H3 and thereby regulates expression of numerous target genes.</p><p>KMT2A is the mammalian homolog of <i>Drosophila</i> Trithorax, which regulates <i>Hox</i> expression. KMT2A is important in hematopoiesis and axial skeletal patterning [<a class="bk_pop" href="#wiedemann-steiner.REF.hess.1997.1799">Hess et al 1997</a>].</p><p><b>Mechanism of disease causation.</b>
|
||
<i>KMT2A</i> pathogenic <a class="def" href="/books/n/gene/glossary/def-item/nonsense-variant/">nonsense</a> variants lead to nonsense-mediated decay, suggesting <a class="def" href="/books/n/gene/glossary/def-item/haploinsufficiency/">haploinsufficiency</a> as the mechanism [<a class="bk_pop" href="#wiedemann-steiner.REF.jones.2012.358">Jones et al 2012</a>]. The pathogenesis of <a class="def" href="/books/n/gene/glossary/def-item/missense/">missense</a> variants may vary by the location, though preliminary studies suggest decreased expression of target genes. The CXXC <a class="def" href="/books/n/gene/glossary/def-item/domain/">domain</a> is thought to be important for binding to target genes and the TAD domain is important for transcriptional activation. A missense variant in the CXXC domain (c.3460C>T; p.Arg1154Trp) resulted in overexpression of the <i>KMT2A</i> transcript and reduction of downstream target genes <i>SIX2</i> and <i>MEIS1</i>, suggestive of impaired DNA binding. Conversely, a missense variant in the TAD domain (c.8558T>G; p.Met2853Trp) did not lead to significant changes in transcript level, but also resulted in a significant reduction in <i>SIX2</i> and <i>MEIS1</i> transcript, suggesting an issue with transcriptional activation [<a class="bk_pop" href="#wiedemann-steiner.REF.lebrun.2018.107">Lebrun et al 2018</a>].</p></div><div id="wiedemann-steiner.Cancer_and_Benign_Tumo"><h3>Cancer and Benign Tumors</h3><p>About 10% of all pediatric and adult leukemias are caused by more than 90 different fusions involving <i>KMT2A</i>, which are thought to lead to disordered <a class="def" href="/books/n/gene/glossary/def-item/epigenetic/">epigenetic</a> regulation and thus abnormal <a class="def" href="/books/n/gene/glossary/def-item/gene/">gene</a> transcription [<a class="bk_pop" href="#wiedemann-steiner.REF.winters.2017.4">Winters & Bernt 2017</a>, <a class="bk_pop" href="#wiedemann-steiner.REF.meyer.2018.273">Meyer et al 2018</a>].</p><p>There is a single report of a family including three sibs with primary mediastinal large B-cell lymphoma and their cousin with diffuse large B-cell lymphoma, both subtypes of non-Hodgkin lymphoma, with a variant in <i>KMT2A</i> (referred to as <i>MLL</i> 5533C>A [His1845Asn] in the article) discovered via <a class="def" href="/books/n/gene/glossary/def-item/exome-sequencing/">exome sequencing</a>. This variant was also found in three healthy family members. The variant was not found in 86 healthy Finnish controls, 92 <a class="def" href="/books/n/gene/glossary/def-item/sporadic/">sporadic</a> non-Hodgkin lymphoma cases, or 14 <a class="def" href="/books/n/gene/glossary/def-item/familial/">familial</a> non-Hodgkin lymphoma cases that were screened [<a class="bk_pop" href="#wiedemann-steiner.REF.saarinen.2013.3428">Saarinen et al 2013</a>].</p></div></div><div id="wiedemann-steiner.Chapter_Notes"><h2 id="_wiedemann-steiner_Chapter_Notes_">Chapter Notes</h2><div id="wiedemann-steiner.Acknowledgments"><h3>Acknowledgments</h3><p>We thank the participants and their families and our co-authors [<a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al 2021</a>]. This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR001880 (S.E.S.). Figures included in this chapter are adapted from <a class="bk_pop" href="#wiedemann-steiner.REF.sheppard.2021.1649">Sheppard et al [2021]</a>.</p></div><div id="wiedemann-steiner.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>26 May 2022 (ma) Review posted live</div></li><li class="half_rhythm"><div>3 August 2021 (fqr) Original submission</div></li></ul></div></div><div id="wiedemann-steiner.References"><h2 id="_wiedemann-steiner_References_">References</h2><div id="wiedemann-steiner.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.aggarwal.2017.285">Aggarwal A, Rodriguez-Buritica DF, Northrup H. Wiedemann-Steiner syndrome: novel pathogenic variant and review of literature. <span><span class="ref-journal">Eur J Med Genet. </span>2017;<span class="ref-vol">60</span>:285–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28359930" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28359930</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.arora.2020.953">Arora V, Puri RD, Bijarnia-Mahay S, Verma IC. Expanding the phenotypic and genotypic spectrum of Wiedemann-Steiner syndrome: first patient from India. <span><span class="ref-journal">Am J Med Genet A. </span>2020;<span class="ref-vol">182</span>:953–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32128942" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32128942</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.baer.2018.141">Baer S, Afenjar A, Smol T, Piton A, Gérard B, Alembik Y, Bienvenu T, Boursier G, Boute O, Colson C, Cordier MP, Cormier-Daire V, Delobel B, Doco-Fenzy M, Duban-Bedu B, Fradin M, Geneviève D, Goldenberg A, Grelet M, Haye D, Heron D, Isidor B, Keren B, Lacombe D, Lèbre AS, Lesca G, Masurel A, Mathieu-Dramard M, Nava C, Pasquier L, Petit A, Philip N, Piard J, Rondeau S, Saugier-Veber P, Sukno S, Thevenon J, Van-Gils J, Vincent-Delorme C, Willems M, Schaefer E, Morin G. Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: a study of 33 French cases. <span><span class="ref-journal">Clin Genet. </span>2018;<span class="ref-vol">94</span>:141–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29574747" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29574747</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.beighton.1970.158">Beighton P. Familial hypertrichosis cubiti: hairy elbows syndrome. <span><span class="ref-journal">J Med Genet. </span>1970;<span class="ref-vol">7</span>:158–60.</span> [<a href="/pmc/articles/PMC1468803/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1468803</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/5519603" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5519603</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.biesecker.2021.8">Biesecker LG, Adam MP, Alkuraya FS, Amemiya AR, Bamshad MJ, Beck AE, Bennett JT, Bird LM, Carey JC, Chung B, Clark RD, Cox TC, Curry C, Dinulos MBP, Dobyns WB, Giampietro PF, Girisha KM, Glass IA, Graham JM Jr, Gripp KW, Haldeman-Englert CR, Hall BD, Innes AM, Kalish JM, Keppler-Noreuil KM, Kosaki K, Kozel BA, Mirzaa GM, Mulvihill JJ, Nowaczyk MJM, Pagon RA, Retterer K, Rope AF, Sanchez-Lara PA, Seaver LH, Shieh JT, Slavotinek AM, Sobering AK, Stevens CA, Stevenson DA, Tan TY, Tan WH, Tsai AC, Weaver DD, Williams MS, Zackai E, Zarate YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics. <span><span class="ref-journal">Am J Hum Genet. </span>2021;<span class="ref-vol">108</span>:8–15.</span> [<a href="/pmc/articles/PMC7820621/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7820621</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33417889" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33417889</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.bogaert.2017.3702">Bogaert DJ, Dullaers M, Kuehn HS, Leroy BP, Niemela JE, De Wilde H, De Schryver S, De Bruyne M, Coppieters F, Lambrecht BN, De Baets F, Rosenzweig SD, De Baere E, Haerynck F. Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes. <span><span class="ref-journal">Sci Rep. </span>2017;<span class="ref-vol">7</span>:3702.</span> [<a href="/pmc/articles/PMC5473876/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5473876</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28623346" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28623346</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.bramswig.2015.553">Bramswig NC, Lüdecke HJ, Alanay Y, Albrecht B, Barthelmie A, Boduroglu K, Braunholz D, Caliebe A, Chrzanowska KH, Czeschik JC, Endele S, Graf E, Guillén-Navarro E, Kiper PÖ, López-González V, Parenti I, Pozojevic J, Utine GE, Wieland T, Kaiser FJ, Wollnik B, Strom TM, Wieczorek D. Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes. <span><span class="ref-journal">Hum Genet. </span>2015;<span class="ref-vol">134</span>:553–68.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25724810" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25724810</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.calvel.2015.289">Calvel P, Kusz-Zamelczyk K, Makrythanasis P, Janecki D, Borel C, Conne B, Vannier A, Béna F, Gimelli S, Fichna P, Antonarakis SE, Nef S, Jaruzelska J. A case of Wiedemann-Steiner syndrome associated with a 46,XY disorder of sexual development and gonadal dysgenesis. <span><span class="ref-journal">Sex Dev. </span>2015;<span class="ref-vol">9</span>:289–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26544196" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26544196</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.chan.2019.9">Chan AJS, Cytrynbaum C, Hoang N, Ambrozewicz PM, Weksberg R, Drmic I, Ritzema A, Schachar R, Walker S, Uddin M, Zarrei M, Yuen RKC, Scherer SW. Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants. <span><span class="ref-journal">NPJ Genom Med. </span>2019;<span class="ref-vol">4</span>:9.</span> [<a href="/pmc/articles/PMC6486600/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6486600</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31044088" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31044088</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.chen.2019.5555">Chen M, Liu R, Wu C, Li X, Wang Y. A novel de novo mutation (p.Pro1310Glnfs*46) in KMT2A caused Wiedemann-Steiner syndrome in a Chinese boy with postnatal growth retardation: a case report. <span><span class="ref-journal">Mol Biol Rep. </span>2019;<span class="ref-vol">46</span>:5555–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31250358" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31250358</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.demir.2021.46">Demir S, Gürkan H, Öz V, Yalçıntepe S, Atlı EI, Atlı E. Wiedemann-Steiner syndrome as a differential diagnosis of Cornelia de Lange syndrome using targeted next-generation sequencing: a case report. <span><span class="ref-journal">Mol Syndromol. </span>2021;<span class="ref-vol">12</span>:46–51.</span> [<a href="/pmc/articles/PMC7983614/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7983614</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33776627" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33776627</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.di_fede.2021.88">Di Fede E, Massa V, Augello B, Squeo G, Scarano E, Perri AM, Fischetto R, Causio FA, Zampino G, Piccione M, Curridori E, Mazza T, Castellana S, Larizza L, Ghelma F, Colombo EA, Gandini MC, Castori M, Merla G, Milani D, Gervasini C. Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann-Steiner and Rubinstein-Taybi syndromes. <span><span class="ref-journal">Eur J Hum Genet. </span>2021;<span class="ref-vol">29</span>:88–98.</span> [<a href="/pmc/articles/PMC7852672/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7852672</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32641752" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32641752</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.enokizono.2017.2821">Enokizono T, Ohto T, Tanaka R, Tanaka M, Suzuki H, Sakai A, Imagawa K, Fukushima H, Iwabuti A, Fukushima T, Sumazaki R, Uehara T, Takenouchi T, Kosaki K. Preaxial polydactyly in an individual with Wiedemann-Steiner syndrome caused by a novel nonsense mutation in KMT2A. <span><span class="ref-journal">Am J Med Genet A. </span>2017;<span class="ref-vol">173</span>:2821–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28815892" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28815892</span></a>]</div></li><li class="half_rhythm"><div class="bk_ref" id="wiedemann-steiner.REF.feldman.2019.300">Feldman HR, Dlouhy SR, Lah MD, Payne KK, Weaver DD. 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A novel deletion mutation in KMT2A identified in a child with ID/DD and blood eosinophilia. <span><span class="ref-journal">BMC Med Genet. </span>2019;<span class="ref-vol">20</span>:38.</span> [<a href="/pmc/articles/PMC6402113/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6402113</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30841869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30841869</span></a>]</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div>
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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/NBK580718/?report=reader">PubReader</a></li><li><a href="/books/NBK580718/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK580718" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK580718" style="display:none" title="Cite this Page"><div class="bk_tt">Sheppard SE, Quintero-Rivera F. Wiedemann-Steiner Syndrome. 2022 May 26. 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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> CTCF-Related Disorder.</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> CTCF-Related Disorder.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Valverde de Morales HG, Wang HL, Garber K, Corces V, Li H. </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 class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/28406602" ref="ordinalpos=1&linkpos=2&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> Myhre Syndrome.</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> Myhre Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Lin AE, Brunetti-Pierri N, Lindsay ME, Schimmenti LA, Starr LJ. </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 class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/39083629" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NFIX-Related Malan Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> NFIX-Related Malan Syndrome.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Priolo M. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">GeneReviews(®). 1993</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/20301377" ref="ordinalpos=1&linkpos=4&log$=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> Phelan-McDermid Syndrome-SHANK3 Related.</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> Phelan-McDermid Syndrome-SHANK3 Related.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">Phelan K, Rogers RC, Boccuto L. </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 class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/31145570" ref="ordinalpos=1&linkpos=5&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> Apert Syndrome.</a><span class="source">[GeneReviews(®). 1993]</span><div 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