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Entry
- #117550 - SOTOS SYNDROME; SOTOS
- OMIM
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<span class="h4">#117550</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/117550"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#nomenclature">Nomenclature</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#heterogeneity">Heterogeneity</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=SOTOS SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0112103" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/117550" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0112103" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:117550" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 75968004<br />
<strong>ICD10CM:</strong> Q87.3<br />
<strong>ORPHA:</strong> 821<br />
<strong>DO:</strong> 0112103<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
117550
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
SOTOS SYNDROME; SOTOS
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CEREBRAL GIGANTISM<br />
CHROMOSOME 5q35 DELETION SYNDROME<br />
SOTOS SYNDROME 1, FORMERLY; SOTOS1, FORMERLY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/800?start=-3&limit=10&highlight=800">
5q35.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Sotos syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117550"> 117550 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
NSD1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606681"> 606681 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/117550" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/117550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/117550" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Mean full term birth length 55.2cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861719&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861719</a>]</span><br /> -
Length at or greater than 97th percentile through early adolescence <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861720&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861720</a>]</span><br /> -
Adult height often normal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861721&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861721</a>]</span><br /> -
Mean male adult height 184.3cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861722&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861722</a>]</span><br /> -
Mean female adult height 172.9cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861723&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861723</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Mean full term birth weight 3.9kg <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861724&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861724</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Birth length often more increased than weight <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861725&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861725</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Dolichocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72239002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72239002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221358&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221358</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000268</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000268" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000268</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Dolichocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Prognathism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72855002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72855002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109504005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109504005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22810007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22810007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.213" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.213</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0399526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0399526</a>, <a href="https://bioportal.bioontology.org/search?q=C0033324&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033324</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Prognathism-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Pointed chin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844505&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844505</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000307</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000307</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7974ac288cfc8dbf20fe3f16a7844d32" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Chin,Pointed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7974ac288cfc8dbf20fe3f16a7844d32&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Otitis media <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65363002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65363002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H66.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H66.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H66.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H66.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/382.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">382.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000388</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000388</a>]</span><br /> -
Conductive hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44057004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44057004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018777&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018777</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000405</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Downslanting palpebral fissures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246800008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246800008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423110&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423110</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000494" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000494</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000494" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000494</a>]</span><br /> -
Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
Hyperopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38101003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38101003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- High arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=c606b0119d4a894ebd5ee0242c136e29" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Palate,High-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=c606b0119d4a894ebd5ee0242c136e29&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Premature tooth eruption <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16000003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16000003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266054&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266054</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006288</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006288</a>]</span><br /> -
Tooth agenesis, first and second premolars <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549563</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Atrial septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Patent ductus arteriosus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83330001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83330001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/747.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">747.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Advanced bone age <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123982003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123982003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0545053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0545053</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005616</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005616</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Joint laxity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298203008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298203008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a>, <a href="https://bioportal.bioontology.org/search?q=C0086437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br /> -
Genu valgum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299330008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299330008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52012001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52012001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.06" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.06</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158484</a>, <a href="https://bioportal.bioontology.org/search?q=C0576093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span><br /> -
Long arm span <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835106&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835106</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Large hands <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249752003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249752003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426870&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426870</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001176" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001176</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001176" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001176</a>]</span><br /> -
Disharmonic maturation of phalanges and carpal bones <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861726&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861726</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pes planus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23407003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23407003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203534009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203534009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53226007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53226007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.61</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/734" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">734</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016202</a>, <a href="https://bioportal.bioontology.org/search?q=C0392477&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392477</a>, <a href="https://bioportal.bioontology.org/search?q=C0264133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0264133</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001763" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001763</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001763" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001763</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=1f893093d35c2d1df583eed57a47b6cb" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Pes_Planus-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=1f893093d35c2d1df583eed57a47b6cb&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Large feet <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299462005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299462005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576225&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576225</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001833" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001833</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001833" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001833</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Nails </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin brittle fingernails <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861727&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861727</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sparse hair in frontoparietal area <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861728&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861728</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Variable mental retardation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859755&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859755</a>]</span><br /> -
Neonatal hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/240080003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">240080003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205294008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33010005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33010005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/P94.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">P94.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0343239&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0343239</a>, <a href="https://bioportal.bioontology.org/search?q=C0270971&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270971</a>, <a href="https://bioportal.bioontology.org/search?q=C2267233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2267233</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span><br /> -
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
Poor coordination <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0563243&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0563243</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002370" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002370</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002370" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002370</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Behavioral problems <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/277843001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">277843001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5886745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5886745</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000708" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000708</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000708" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000708</a>]</span><br /> -
Expressive language delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229734008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229734008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0454641&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0454641</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002474</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002474</a>]</span><br /> -
Partial to complete agenesis of corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857278&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857278</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001338" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001338</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001338" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001338</a>]</span><br /> -
Persistent cavum septum pellucidum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002389</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002389</a>]</span><br /> -
Large cisterna magna <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002280</a>]</span><br /> -
Ventriculomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413808003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413808003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1531647&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1531647</a>, <a href="https://bioportal.bioontology.org/search?q=C3278923&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278923</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002119" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002119</a>]</span><br /> -
Prominent trigone and occipital horns <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861718&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861718</a>]</span><br />
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<strong> NEOPLASIA </strong>
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- Wilms tumor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25081006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25081006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027708&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027708</a>, <a href="https://bioportal.bioontology.org/search?q=C1333015&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1333015</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002667" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002667</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002667" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002667</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- De novo mutation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2985439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2985439</a>]</span><br /> -
Majority of cases are sporadic<br /> -
Few familial (parent offspring) cases reported<br /> -
Slight increased risk for malignancy<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the nuclear receptor binding SET domain protein 1 gene (NSD1, <a href="/entry/606681#0001">606681.0001</a>)<br />
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<p>A number sign (#) is used with this entry because Sotos syndrome (SOTOS) is caused by heterozygous mutation in the NSD1 gene (<a href="/entry/606681">606681</a>) or by a deletion in the 5q35 region including genomic sequence in addition to the NSD1 gene.</p>
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<strong>Description</strong>
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<p>Sotos syndrome (SOTOS) is a neurologic disorder characterized by overgrowth from the prenatal stage through childhood, with advanced bone age, an unusual face with large skull, acromegalic features and pointed chin, occasional brain anomalies and seizures, and impaired intellectual development (summary by <a href="#34" class="mim-tip-reference" title="Kurotaki, N., Imaizumi, K., Harada, N., Masuno, M., Kondoh, T., Nagai, T., Ohashi, H., Naritomi, K., Tsukahara, M., Makita, Y., Sugimoto, T., Sonoda, T., and 11 others. &lt;strong&gt;Haploinsufficiency of NSD1 causes Sotos syndrome.&lt;/strong&gt; Nature Genet. 30: 365-366, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11896389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11896389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng863&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11896389">Kurotaki et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11896389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Weaver syndrome (<a href="/entry/277590">277590</a>), which shows considerable phenotypic overlap with Sotos syndrome, has been shown to be caused by mutation in the EZH2 gene (<a href="/entry/601573">601573</a>) on chromosome 7q36.</p>
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<p><a href="#51" class="mim-tip-reference" title="Sotos, J. F., Dodge, P. R., Muirhead, D., Crawford, J. D., Talbot, N. B. &lt;strong&gt;Cerebral gigantism in childhood: a syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder.&lt;/strong&gt; New Eng. J. Med. 271: 109-116, 1964.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14148233/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14148233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196407162710301&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14148233">Sotos et al. (1964)</a> described 5 children with a disorder characterized by excessively rapid growth, acromegalic features, and a nonprogressive cerebral disorder with mental retardation. High-arched palate and prominent jaw were noted in several of them. Birth length was between the 90th and 97th centiles in all. Bone age was advanced in most. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14148233" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Hook, E. B., Reynolds, J. W. &lt;strong&gt;Cerebral gigantism: endocrinological and clinical observations of six patients including a congenital giant, concordant monozygotic twins, and a child who achieved adult gigantic size.&lt;/strong&gt; J. Pediat. 70: 900-914, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4290694/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4290694&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(67)80263-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4290694">Hook and Reynolds (1967)</a> reported that affected children have large hands and feet from birth. Growth is rapid in the first years of life but final height may not be excessive. Bone age is advanced. The skull is large with moderate prognathism. Mild dilation of the cerebral ventricles, nonspecific EEG changes, and seizures have been observed. Poor coordination and mental retardation are features. In 2 patients, <a href="#4" class="mim-tip-reference" title="Bejar, R. L., Smith, G. F., Park, S., Spellacy, W. N., Wolfson, S. L., Nyhan, W. L. &lt;strong&gt;Cerebral gigantism: concentrations of amino acids in plasma and muscle.&lt;/strong&gt; J. Pediat. 76: 105-111, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4312004/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4312004&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(70)80138-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4312004">Bejar et al. (1970)</a> found abnormal dermatoglyphics, normal growth hormone levels, and high levels of valine, isoleucine and leucine in the blood. The glycine-to-valine ratio seemed particularly useful in distinguishing patients from controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4290694+4312004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Ruvalcaba, R. H. A., Myhre, S., Smith, D. W. &lt;strong&gt;Sotos syndrome with intestinal polyposis and pigmentary changes of the genitalia.&lt;/strong&gt; Clin. Genet. 18: 413-416, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7449178/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7449178&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1980.tb01785.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7449178">Ruvalcaba et al. (1980)</a> found hamartomatous polyps of the intestine and melanin spots of the penis in 2 males with the Sotos syndrome. <a href="#22" class="mim-tip-reference" title="Halal, F. &lt;strong&gt;Cerebral gigantism, intestinal polyposis, and pigmentary spotting of the genitalia. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 15: 161, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6859117/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6859117&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320150125&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6859117">Halal (1983)</a> reported that the older of the boys she reported with cerebral gigantism had pigmented spots on the genitalia and that the father had been found to have a rectal polyp--findings like those in the 2 unrelated adult males reported by <a href="#45" class="mim-tip-reference" title="Ruvalcaba, R. H. A., Myhre, S., Smith, D. W. &lt;strong&gt;Sotos syndrome with intestinal polyposis and pigmentary changes of the genitalia.&lt;/strong&gt; Clin. Genet. 18: 413-416, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7449178/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7449178&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1980.tb01785.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7449178">Ruvalcaba et al. (1980)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6859117+7449178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Kaneko, H., Tsukahara, M., Tachibana, H., Kurashige, H., Kuwano, A., Kajii, T. &lt;strong&gt;Congenital heart defects in Sotos sequence.&lt;/strong&gt; Am. J. Med. Genet. 26: 569-576, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3565472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3565472&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320260310&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3565472">Kaneko et al. (1987)</a> found congenital heart defects in 5 of 10 patients with typical Sotos syndrome. <a href="#42" class="mim-tip-reference" title="Noreau, D. R., Al-Ata, J., Jutras, L., Teebi, A. S. &lt;strong&gt;Congenital heart defects in Sotos syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 327-328, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781915/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781915&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;327::aid-ajmg16&gt;3.0.co;2-t&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781915">Noreau et al. (1998)</a> found that 3 of 14 Sotos syndrome patients had congenital heart defects. In a literature review, they found another 17 patients with variable cardiac defects, mostly closure defects, making an overall incidence of approximately 8%. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9781915+3565472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Goldstein, D. J., Ward, R. E., Moore, E., Fremion, A. S., Wappner, R. S. &lt;strong&gt;Overgrowth, congenital hypotonia, nystagmus, strabismus, and mental retardation: variant of dominantly inherited Sotos sequence?&lt;/strong&gt; Am. J. Med. Genet. 29: 783-792, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3400723/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3400723&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320290408&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3400723">Goldstein et al. (1988)</a> described 2 unrelated children with macrocephaly, excessive growth, strabismus, hypotonia and developmental delay, and improvement with age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3400723" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review, <a href="#10" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. &lt;strong&gt;Sotos syndrome.&lt;/strong&gt; J. Med. Genet. 27: 571-576, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2231650/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2231650&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.27.9.571&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2231650">Cole and Hughes (1990)</a> emphasized that the handicaps in Sotos syndrome are fewer than previously believed and tend to improve with age. The latter feature makes identification of affected adults difficult. <a href="#11" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. &lt;strong&gt;Sotos syndrome: a study of the diagnostic criteria and natural history.&lt;/strong&gt; J. Med. Genet. 31: 20-32, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7512144/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7512144&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.31.1.20&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7512144">Cole and Hughes (1994)</a> clinically assessed 79 patients with a provisional diagnosis of Sotos syndrome and evaluated their photographs between ages 1 and 6 years. These photographs, together with photographs of first-degree relatives, also at ages 1 to 6 years, were reviewed by 4 clinical geneticists. In 41 probands, but no first-degree relatives, the facial gestalt was thought to be characteristic of Sotos syndrome. Comparison of anthropometric measurements, bone age, and developmental delay in these 41 probands showed marked differences between them and the remaining 38 probands. Length was identified as the most significantly increased prenatal parameter. In childhood, occipitofrontal head circumference (OFC), height, and weight were all increased. OFC remained above the 97th percentile in all but one case throughout childhood and adulthood, whereas height and weight had a tendency to return toward the mean. This 'normalization' was more pronounced in females and was probably related to their early puberty. Early developmental delay and an advanced bone age were seen in 100% and 84% of cases, respectively. <a href="#11" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. &lt;strong&gt;Sotos syndrome: a study of the diagnostic criteria and natural history.&lt;/strong&gt; J. Med. Genet. 31: 20-32, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7512144/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7512144&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.31.1.20&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7512144">Cole and Hughes (1994)</a> suggested that facial gestalt, growth pattern, bone age, and developmental delay are the major diagnostic criteria. Using these criteria, no affected first-degree relatives were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7512144+2231650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Scarpa, P., Faggioli, R., Voghenzi, A. &lt;strong&gt;Familial Sotos syndrome: longitudinal study of two additional cases.&lt;/strong&gt; Genet. Counsel. 5: 155-159, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7917124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7917124&lt;/a&gt;]" pmid="7917124">Scarpa et al. (1994)</a> described a sister and brother with macrocrania and coarse face (frontal bossing, highly arched palate, prognathism, pointed chin, large ears). Psychomotor development of the sister, who also had advanced osseous maturation, improved significantly at the age of 7 years. Accelerated growth with normal bone age, optic atrophy, renal agenesis with contralateral double kidney, and significant mental retardation (IQ, 45) were shown in the brother at 3.5 years of age. The father of these children was tall, with macrocrania and large hands and feet. He had had learning difficulties in school and was a manual laborer. <a href="#46" class="mim-tip-reference" title="Scarpa, P., Faggioli, R., Voghenzi, A. &lt;strong&gt;Familial Sotos syndrome: longitudinal study of two additional cases.&lt;/strong&gt; Genet. Counsel. 5: 155-159, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7917124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7917124&lt;/a&gt;]" pmid="7917124">Scarpa et al. (1994)</a> suggested that these children and their father showed different manifestations of Sotos syndrome. <a href="#1" class="mim-tip-reference" title="Allanson, J. E., Cole, T. R. P. &lt;strong&gt;Sotos syndrome: evolution of facial phenotype subjective and objective assessment.&lt;/strong&gt; Am. J. Med. Genet. 65: 13-20, 1996. Note: Erratum: Am. J. Med. Genet. 79: 229-230, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8914735/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8914735&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1&lt;13::AID-AJMG2&gt;3.0.CO;2-Z&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8914735">Allanson and Cole (1996)</a> presented anthropometric evaluation of the head in 45 patients with Sotos syndrome between age 1 and 25 years. With increasing age, the face lengthens and the chin becomes more striking. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7917124+8914735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Opitz, J. M., Weaver, D. W., Reynolds, J. F., Jr. &lt;strong&gt;The syndromes of Sotos and Weaver: reports and review.&lt;/strong&gt; Am. J. Med. Genet. 79: 294-304, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781911/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;294::aid-ajmg12&gt;3.0.co;2-m&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781911">Opitz et al. (1998)</a> reported an affected mother and daughter. The mother was described as a large infant and 'as tall as her teacher in school.' Her adult height was 185.4 cm, and she had mandibular prognathism and a prominent pointed chin. The daughter showed a prominent forehead with sparseness of frontal hair and a 'ruddy' or flushed complexion, especially of the nose and perioral area. She had prominent features of the congenital hypotonia/lymphedema sequence with hypermobile joints, especially at the knees and ankles, lymphedema nails (especially toenails), and a high total ridge count (TRC) of the fingertip dermatoglyphics. The mother also had a high TRC and a receding frontal hairline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9781911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#44" class="mim-tip-reference" title="Robertson, S. P., Bankier, A. &lt;strong&gt;Sotos syndrome and cutis laxa.&lt;/strong&gt; J. Med. Genet. 36: 51-56, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9950366/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9950366&lt;/a&gt;]" pmid="9950366">Robertson and Bankier (1999)</a> reported 3 children with anthropometric and dysmorphologic features of classic Sotos syndrome in association with redundant skin folds, joint hypermobility, and, in 2 of the 3, vesicoureteric reflux. <a href="#44" class="mim-tip-reference" title="Robertson, S. P., Bankier, A. &lt;strong&gt;Sotos syndrome and cutis laxa.&lt;/strong&gt; J. Med. Genet. 36: 51-56, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9950366/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9950366&lt;/a&gt;]" pmid="9950366">Robertson and Bankier (1999)</a> thought the associated features suggested a coexisting connective tissue disorder. All the patients had a normal bone age. Although Sotos syndrome in its classically described form was not present, <a href="#44" class="mim-tip-reference" title="Robertson, S. P., Bankier, A. &lt;strong&gt;Sotos syndrome and cutis laxa.&lt;/strong&gt; J. Med. Genet. 36: 51-56, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9950366/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9950366&lt;/a&gt;]" pmid="9950366">Robertson and Bankier (1999)</a> concluded that this entity might reflect a related, perhaps allelic, condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9950366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#53" class="mim-tip-reference" title="Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. &lt;strong&gt;Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.&lt;/strong&gt; Am. J. Hum. Genet. 77: 193-204, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15942875/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15942875&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432082&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15942875">Tatton-Brown et al. (2005)</a> reviewed the clinical phenotype of 239 individuals with NSD1 abnormalities and found that facial dysmorphism, learning disability, and childhood overgrowth were present in 90% of individuals; however, both height and head circumference were within the normal range in 10% of individuals, indicating that overgrowth is not obligatory for the diagnosis of Sotos syndrome. A broad spectrum of associated clinical features was also present, the occurrence of which was largely independent of genotype: individuals with identical mutations had different phenotypes, all features present in patients with microdeletions were also observed in patients with mutations, and there was no correlation between deletion size and clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15942875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Kotilainen, J., Pohjola, P., Pirinen, S., Arte, S., Nieminen, P. &lt;strong&gt;Premolar hypodontia is a common feature in Sotos syndrome with a mutation in the NSD1 gene.&lt;/strong&gt; Am. J. Med. Genet. 149A: 2409-2414, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19876911/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19876911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33062&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19876911">Kotilainen et al. (2009)</a> studied the dental manifestations of Sotos syndrome and found that one or more premolar teeth were absent in 9 (69%) of 13 affected children and adolescents. All of the patients with hypodontia had a heterozygous mutation in the NSD1 gene. The patient with the most severe phenotype of tooth agenesis, involving not only the second premolars and third molars but also 1 mandibular incisor, had a microdeletion encompassing the entire NSD1 gene, whereas the 4 patients with the mildest tooth phenotype included both patients with only missense mutations, suggesting that the severity of tooth agenesis might be related to the type of mutation. More than half of the patients had enamel defects or excessive tooth wear. Dental age, based on tooth formation, was within the normal range. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19876911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Fryssira, H., Drossatou, P., Sklavou, R., Barambouti, F., Manolaki, N. &lt;strong&gt;Two cases of Sotos syndrome with novel mutations of the NSD1 gene.&lt;/strong&gt; Genet. Counsel. 21: 53-59, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20420030/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20420030&lt;/a&gt;]" pmid="20420030">Fryssira et al. (2010)</a> reported 2 boys with typical features of Sotos syndrome and mutations in the NSD1 gene; 1 patient also had cryptorchidism and vertebral anomalies. The authors noted that despite the wide range of phenotypic features, molecular analysis can correctly identify Sotos syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20420030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Grand, K., Gonzalez-Gandolfi, C., Ackermann, A. M., Aljeaid, D., Bedoukian, E., Bird, L. M., De Leon, D. D., Diaz, J., Hopkin, R. J., Kadakia, S. P., Keena, B., Klein, K. O., and 11 others. &lt;strong&gt;Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.&lt;/strong&gt; Am. J. Med. Genet. 179A: 542-551, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30719864/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30719864&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30719864[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61062&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30719864">Grand et al. (2019)</a> reported 7 patients with Sotos syndrome with mutations in the NSD1 gene who had hyperinsulinemic hypoglycemia, expanding the phenotypic spectrum of the disorder. The hyperinsulinemic hypoglycemia was persistent beyond a year of life in at least 3 patients; 2 other patients were less than 1 year of age and thus it was not yet known whether it would be persistent. Most of the patients did not have classic features of Sotos syndrome at presentation, with 6 of 7 patients requiring diagnosis by exome sequencing. The authors concluded that NSD1 haploinsufficiency is sufficient to cause hyperinsulinemic hypoglycemia, suggesting a role for NSD1 in glucose hemostasis. They recommended that Sotos syndrome be considered in neonates presenting with hyperinsulinemic hypoglycemia. All patients had some response when treated with diazoxide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30719864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Tumor Formation</em></strong></p><p>
<a href="#38" class="mim-tip-reference" title="Maldonado, V., Gaynon, P. S., Poznanski, A. K. &lt;strong&gt;Cerebral gigantism associated with Wilms&#x27; tumor.&lt;/strong&gt; Am. J. Dis. Child. 138: 486-488, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6324572/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6324572&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archpedi.1984.02140430062016&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6324572">Maldonado et al. (1984)</a> reported the association of malignant tumors in Sotos syndrome. <a href="#41" class="mim-tip-reference" title="Nance, M. A., Neglia, J. P., Talwar, D., Berry, S. A. &lt;strong&gt;Neuroblastoma in a patient with Sotos&#x27; syndrome.&lt;/strong&gt; J. Med. Genet. 27: 130-132, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2319581/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2319581&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.27.2.130&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2319581">Nance et al. (1990)</a> described a 15-month-old child with Sotos syndrome and a paraspinal neuroblastoma. From this and other evidence, they concluded that children with this disorder may be at an increased risk for developing tumors. <a href="#19" class="mim-tip-reference" title="Gorlin, R. J., Cohen, M. M., Levin L. S. &lt;strong&gt;Overgrowth syndromes and postnatal onset obesity syndromes. Syndromes of the Head and Neck. (3rd ed.)&lt;/strong&gt; New York: Oxford Univ. Press (pub.) 1990. Pp. 323-352."None>Gorlin et al. (1990)</a> estimated a risk of 3.9% of benign or malignant tumors in Sotos syndrome. The same excess of neoplasms is present in other overgrowth syndromes. <a href="#36" class="mim-tip-reference" title="Le Marec, B., Pasquier, L., Dugast, C., Gosselin, M., Odent, S. &lt;strong&gt;Gastric carcinoma in Sotos syndrome (cerebral gigantism).&lt;/strong&gt; Ann. Genet. 42: 113-116, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10434127/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10434127&lt;/a&gt;]" pmid="10434127">Le Marec et al. (1999)</a> reported that one of a monozygotic twin pair, both of whom had Sotos syndrome, developed a diffuse gastric carcinoma containing signet ring cells at the age of 26. The young age of occurrence of this gastric carcinoma suggested a genetic factor. <a href="#37" class="mim-tip-reference" title="Leonard, N. J., Cole, T., Bhargava, R., Honore, L. H., Watt, J. &lt;strong&gt;Sacrococcygeal teratoma in two cases of Sotos syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 95: 182-184, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11078573/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11078573&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1096-8628(20001113)95:2&lt;182::aid-ajmg18&gt;3.0.co;2-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11078573">Leonard et al. (2000)</a> reported 2 children with Sotos syndrome who had benign sacrococcygeal teratomas. Given that Sotos syndrome and sacrococcygeal teratoma are rare events, the authors suggested that these tumors may be due to the effects of overgrowth on tumor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11078573+2319581+6324572+10434127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Two of 7 patients reported by <a href="#20" class="mim-tip-reference" title="Grand, K., Gonzalez-Gandolfi, C., Ackermann, A. M., Aljeaid, D., Bedoukian, E., Bird, L. M., De Leon, D. D., Diaz, J., Hopkin, R. J., Kadakia, S. P., Keena, B., Klein, K. O., and 11 others. &lt;strong&gt;Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.&lt;/strong&gt; Am. J. Med. Genet. 179A: 542-551, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30719864/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30719864&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30719864[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61062&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30719864">Grand et al. (2019)</a> with SOTOS syndrome with hyperinsulinemic hypoglycemia and mutation in the NSD1 gene had a sacrococcygeal teratoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30719864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDiagnosisToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Diagnosis</strong>
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<p><a href="#43" class="mim-tip-reference" title="Opitz, J. M., Weaver, D. W., Reynolds, J. F., Jr. &lt;strong&gt;The syndromes of Sotos and Weaver: reports and review.&lt;/strong&gt; Am. J. Med. Genet. 79: 294-304, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781911/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;294::aid-ajmg12&gt;3.0.co;2-m&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781911">Opitz et al. (1998)</a> discussed the differentiation of 2 overgrowth syndromes, Sotos syndrome and Weaver syndrome (<a href="/entry/277590">277590</a>), and the question of whether the similarities are sufficient to consider them 1 entity. They noted that vertebrate development is constrained into only a very few final or common developmental pathways; therefore, no developmental anomaly seen in humans is unique to ('pathognomonic of') one syndrome. Possible phenotypic differences between the syndromes of Sotos and Weaver pointed out by <a href="#43" class="mim-tip-reference" title="Opitz, J. M., Weaver, D. W., Reynolds, J. F., Jr. &lt;strong&gt;The syndromes of Sotos and Weaver: reports and review.&lt;/strong&gt; Am. J. Med. Genet. 79: 294-304, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781911/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;294::aid-ajmg12&gt;3.0.co;2-m&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781911">Opitz et al. (1998)</a> were the following: the Sotos syndrome may be a cancer syndrome, whereas the Weaver syndrome is not (although a neuroblastoma had been reported in the latter disorder). In Sotos syndrome there is remarkably advanced dental maturation; this is rarely commented on in Weaver syndrome. In Weaver syndrome, there are more conspicuous contractures and a facial appearance that experts find convincingly different from that in Sotos syndrome. <a href="#43" class="mim-tip-reference" title="Opitz, J. M., Weaver, D. W., Reynolds, J. F., Jr. &lt;strong&gt;The syndromes of Sotos and Weaver: reports and review.&lt;/strong&gt; Am. J. Med. Genet. 79: 294-304, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781911/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;294::aid-ajmg12&gt;3.0.co;2-m&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781911">Opitz et al. (1998)</a> favored allelic heterogeneity as the explanation for the similarities between Sotos and Weaver syndromes. They suggested that mapping and isolation of the causative gene or genes would settle the issue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9781911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Melchior, L., Schwartz, M., Duno, M. &lt;strong&gt;dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the first 100 Sotos syndrome mutations.&lt;/strong&gt; Ann. Hum. Genet. 69: 222-226, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15720303/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15720303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1529-8817.2004.00150.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15720303">Melchior et al. (2005)</a> developed a denaturing high-performance liquid chromatography (DHPLC) screening protocol for mutation detection in NSD1 that achieved an efficiency of mutation detection comparable to that of direct sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15720303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Differential Diagnosis</em></strong></p><p>
<a href="#47" class="mim-tip-reference" title="Schaefer, G. B., Bodensteiner, J. B., Buehler, B. A., Lin, A., Cole, T. R. P. &lt;strong&gt;The neuroimaging findings in Sotos syndrome.&lt;/strong&gt; Am. J. Med. Genet. 68: 462-465, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9021022/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9021022&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19970211)68:4&lt;462::aid-ajmg18&gt;3.0.co;2-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9021022">Schaefer et al. (1997)</a> concluded that neuroimaging findings of Sotos syndrome are distinct enough to allow differentiation of this syndrome from other mental retardation syndromes with macrocephaly. The most common abnormality of the cerebral ventricles was prominence of the trigone (90%), followed by prominence of the occipital horns (75%) and ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were increased for age in 70% of the patients and the fluid spaces in the posterior fossa were increased in 70% also. A variety of midline abnormalities were noted but anomalies of the corpus callosum were almost universal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9021022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="nomenclature" class="mim-anchor"></a>
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<strong>Nomenclature</strong>
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<p><a href="#16" class="mim-tip-reference" title="Fryns, J. P. &lt;strong&gt;The Prader-Willi syndrome and the Sotos syndrome: syndromes or sequences? (Letter)&lt;/strong&gt; Clin. Genet. 33: 457-458, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3168318/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3168318&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1988.tb03481.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3168318">Fryns (1988)</a> referred to cases of the fragile X syndrome (FXS; <a href="/entry/300624">300624</a>) in which Sotos syndrome had been diagnosed; he therefore suggested that this disorder be designated the Sotos sequence or the mental retardation-overgrowth sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3168318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
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<strong>Inheritance</strong>
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<p>Most reported cases of Sotos syndrome have been sporadic and may represent new dominant mutations. <a href="#27" class="mim-tip-reference" title="Hook, E. B., Reynolds, J. W. &lt;strong&gt;Cerebral gigantism: endocrinological and clinical observations of six patients including a congenital giant, concordant monozygotic twins, and a child who achieved adult gigantic size.&lt;/strong&gt; J. Pediat. 70: 900-914, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4290694/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4290694&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(67)80263-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4290694">Hook and Reynolds (1967)</a> reported a concordant set of affected identical twins. <a href="#26" class="mim-tip-reference" title="Hooft, C., Schotte, H., Van Hooren, G. &lt;strong&gt;Familial cerebral gigantism.&lt;/strong&gt; Acta Paediat. Belg. 22: 173-186, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5678746/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5678746&lt;/a&gt;]" pmid="5678746">Hooft et al. (1968)</a> described cerebral gigantism in 2 first cousins. <a href="#23" class="mim-tip-reference" title="Hansen, F. J., Friis, B. &lt;strong&gt;Familial occurrence of cerebral gigantism, Sotos&#x27; syndrome.&lt;/strong&gt; Acta Paediat. Scand. 65: 387-389, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1274571/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1274571&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1976.tb04902.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1274571">Hansen and Friis (1976)</a> described affected mother and child. <a href="#58" class="mim-tip-reference" title="Zonana, J., Rimoin, D. L., Fisher, D. A. &lt;strong&gt;Cerebral gigantism--apparent dominant inheritance.&lt;/strong&gt; Birth Defects Orig. Art. Ser. XII(6): 63-69, 1976."None>Zonana et al. (1976)</a> described affected mother and 2 children (male and female). The mother's father may have been affected. <a href="#59" class="mim-tip-reference" title="Zonana, J., Sotos, J. F., Romshe, C. A., Fisher, D. A., Elders, M. J., Rimoin, D. L. &lt;strong&gt;Dominant inheritance of cerebral gigantism.&lt;/strong&gt; J. Pediat. 91: 251-256, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/889595/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;889595&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(77)80822-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="889595">Zonana et al. (1977)</a> reported 3 families showing vertical transmission and equal severity in males and females; no male-to-male transmission was observed. As an addendum, they commented on a fourth instance of affected mother and son. <a href="#49" class="mim-tip-reference" title="Smith, A., Farrar, J. R., Silink, M., Judzewitsch, R. &lt;strong&gt;Investigations in dominant Sotos syndrome.&lt;/strong&gt; Ann. Genet. 24: 226-228, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6977303/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6977303&lt;/a&gt;]" pmid="6977303">Smith et al. (1981)</a> observed affected mother and daughter--the presumed fifth instance of dominant inheritance. The mother had primary hypothyroidism due to Hashimoto disease. <a href="#21" class="mim-tip-reference" title="Halal, F. &lt;strong&gt;Male to male transmission of cerebral gigantism.&lt;/strong&gt; Am. J. Med. Genet. 12: 411-419, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7124794/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7124794&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320120405&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7124794">Halal (1982)</a> reported a family in which the father and 2 of his sons were affected. She knew of no other instance of documented male-to-male transmission. <a href="#57" class="mim-tip-reference" title="Winship, I. M. &lt;strong&gt;Sotos syndrome--autosomal dominant inheritance substantiated.&lt;/strong&gt; Clin. Genet. 28: 243-246, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4064361/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4064361&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1985.tb00393.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4064361">Winship (1985)</a> described a 'Cape Coloured' family with affected father and 4 children by 2 different, unrelated wives. Presumed Sotos syndrome was described in a mother and 2 daughters by <a href="#2" class="mim-tip-reference" title="Bale, A. E., Drum, M. A., Parry, D. M., Mulvihill, J. J. &lt;strong&gt;Familial Sotos syndrome (cerebral gigantism): craniofacial and psychological characteristics.&lt;/strong&gt; Am. J. Med. Genet. 20: 613-624, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2581446/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2581446&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320200407&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2581446">Bale et al. (1985)</a>. They suggested that instances of seemingly autosomal recessive inheritance may be examples of incomplete penetrance, gonadal mosaicism, or genetic heterogeneity. Minor changes in 2 mothers of 2 unrelated affected infants reported by <a href="#18" class="mim-tip-reference" title="Goldstein, D. J., Ward, R. E., Moore, E., Fremion, A. S., Wappner, R. S. &lt;strong&gt;Overgrowth, congenital hypotonia, nystagmus, strabismus, and mental retardation: variant of dominantly inherited Sotos sequence?&lt;/strong&gt; Am. J. Med. Genet. 29: 783-792, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3400723/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3400723&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320290408&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3400723">Goldstein et al. (1988)</a> suggested dominant inheritance of a Sotos sequence. <a href="#6" class="mim-tip-reference" title="Brown, W. T., Wisniewski, K. E., Sudhalter, V., Keogh, M., Tsiouris, J., Miezejeski, C., Schaefer, G. B. &lt;strong&gt;Identical twins discordant for Sotos syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 329-333, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9781916/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9781916&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;329::aid-ajmg17&gt;3.3.co;2-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9781916">Brown et al. (1998)</a> described a pair of 5-year-old male monozygotic twins who were discordant for Sotos syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5678746+4290694+9781916+2581446+4064361+6977303+889595+1274571+3400723+7124794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The possibility of uniparental disomy in Sotos syndrome was investigated by <a href="#50" class="mim-tip-reference" title="Smith, M., Fullwood, P., Qi, Y., Palmer, S., Upadhyaya, M., Cole, T. &lt;strong&gt;No evidence for uniparental disomy as a common cause of Sotos syndrome.&lt;/strong&gt; J. Med. Genet. 34: 10-12, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9032642/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9032642&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.1.10&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9032642">Smith et al. (1997)</a>. Using 112 dinucleotide repeat DNA polymorphisms, they examined parental inheritance of all autosomal pairs, except chromosome 15, in 29 patients with Sotos syndrome. All informative cases showed biparental inheritance and no cases of UPD were found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9032642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="heterogeneity" class="mim-anchor"></a>
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<p>In a study of the metacarpophalangeal pattern profile (MCPP) in Sotos syndrome, <a href="#7" class="mim-tip-reference" title="Butler, M. G., Meaney, F. J., Kittur, S., Hersh, J. H., Hornstein, L. &lt;strong&gt;Metacarpophalangeal pattern profile analysis in Sotos syndrome.&lt;/strong&gt; Am. J. Med. Genet. 20: 625-629, 1985. Note: Erratum: Am. J. Med. Genet. 24: 761 only, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3993685/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3993685&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=3993685[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320200408&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3993685">Butler et al. (1985)</a> found no evidence of heterogeneity and developed a diagnostic tool using MCPP variables, which they suggested may be useful. <a href="#8" class="mim-tip-reference" title="Butler, M. G., Meaney, F. J. &lt;strong&gt;Metacarpophalangeal pattern profile analysis in Sotos syndrome: an update. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 24: 761 only, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3740107/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3740107&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320240421&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3740107">Butler and Meaney (1986)</a> provided an update on the MCPP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3993685+3740107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Mapping</strong>
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<p><a href="#48" class="mim-tip-reference" title="Schrander-Stumpel, C. T. R. M., Fryns, J. P., Hamers, G. G. &lt;strong&gt;Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21)).&lt;/strong&gt; Clin. Genet. 37: 226-229, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2323093/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2323093&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1990.tb03507.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2323093">Schrander-Stumpel et al. (1990)</a> described a 6-year-old boy with Sotos syndrome who also had a de novo, apparently balanced translocation, t(3;6)(p21;p21). They suggested that the autosomal dominant gene for the Sotos syndrome may be located either at 3p21 or 6p21. <a href="#54" class="mim-tip-reference" title="Tsukahara, M., Kajii, T. &lt;strong&gt;High resolution-banded chromosomes from patients with Sotos syndrome. (Letter)&lt;/strong&gt; Clin. Genet. 39: 313-314, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2070551/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2070551&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1991.tb03034.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2070551">Tsukahara and Kajii (1991)</a> could find no abnormality in high resolution-banded chromosomes from 5 patients. Involvement of genes at 3p21 was also suggested by the case reported by <a href="#9" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E., Jeffreys, M. J., Williams, G. T., Arnold, M. M. &lt;strong&gt;Small cell lung carcinoma in a patient with Sotos syndrome: are genes at 3p21 involved in both conditions?&lt;/strong&gt; J. Med. Genet. 29: 338-341, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1316442/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1316442&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.29.5.338&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1316442">Cole et al. (1992)</a>; a 22-year-old female with Sotos syndrome, a nonsmoker, died of small cell lung carcinoma (<a href="/entry/182280">182280</a>) for which genetic determinants in the 3p21 region are suggested by loss-of-heterozygosity studies. <a href="#39" class="mim-tip-reference" title="Maroun, C., Schmerler, S., Hutcheon, R. G. &lt;strong&gt;Child with Sotos phenotype and a 5:15 translocation.&lt;/strong&gt; Am. J. Med. Genet. 50: 291-293, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8042674/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8042674&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320500313&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8042674">Maroun et al. (1994)</a> reported the case of a 4-year-old girl with Sotos phenotype and a de novo balanced translocation between 5q and 15q: 46,XX,t(5,15)(q35;q22). They thus suggested 5q35 or 15q22 as the site of an autosomal dominant gene determining Sotos syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1316442+2323093+8042674+2070551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Faivre, L., Viot, G., Prieur, M., Turleau, C., Gosset, P., Romana, S., Munnich, A., Vekemans, M., Cormier-Daire, V. &lt;strong&gt;Apparent Sotos syndrome (cerebral gigantism) in a child with Trisomy 20p11.2-p12.1 mosaicism.&lt;/strong&gt; Am. J. Med. Genet. 91: 273-276, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10766982/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10766982&lt;/a&gt;]" pmid="10766982">Faivre et al. (2000)</a> reported a child with apparent Sotos syndrome and mosaicism for partial duplication of the short arm of chromosome 20 (46,XY,dup(20)(p12.1-p11.2)[12]/46,XY[66]). The somatostatin receptor-4 (SSTR4; <a href="/entry/182454">182454</a>) gene is located at 20p11.2, encompassed by the duplication. The authors proposed that a dosage effect of this gene might be responsible for some of their patient's clinical findings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10766982" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Imaizumi, K., Kimura, J., Matsuo, M., Kurosawa, K., Masuno, M., Niikawa, N., Kuroki, Y. &lt;strong&gt;Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1).&lt;/strong&gt; Am. J. Med. Genet. 107: 58-60, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11807869/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11807869&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.10080&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11807869">Imaizumi et al. (2002)</a> described a de novo balanced reciprocal translocation between the long arms of chromosomes 5 and 8, 46,XX,t(5;8)(q35;q24.1), in a 15-month-old girl with a typical Sotos syndrome phenotype. They proposed that a gene responsible for this disorder is located in the distal long arm region of chromosome 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11807869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>In patients with Sotos syndrome harboring a chromosomal translocation, <a href="#34" class="mim-tip-reference" title="Kurotaki, N., Imaizumi, K., Harada, N., Masuno, M., Kondoh, T., Nagai, T., Ohashi, H., Naritomi, K., Tsukahara, M., Makita, Y., Sugimoto, T., Sonoda, T., and 11 others. &lt;strong&gt;Haploinsufficiency of NSD1 causes Sotos syndrome.&lt;/strong&gt; Nature Genet. 30: 365-366, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11896389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11896389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng863&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11896389">Kurotaki et al. (2002)</a> isolated the NSD1 (<a href="/entry/606681">606681</a>) gene from the 5q35 breakpoint. They identified 1 nonsense, 3 frameshift, and 20 submicroscopic deletion mutations of NSD1 among 42 sporadic cases of Sotos syndrome. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11896389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To the 42 cases of Sotos syndrome reported by <a href="#34" class="mim-tip-reference" title="Kurotaki, N., Imaizumi, K., Harada, N., Masuno, M., Kondoh, T., Nagai, T., Ohashi, H., Naritomi, K., Tsukahara, M., Makita, Y., Sugimoto, T., Sonoda, T., and 11 others. &lt;strong&gt;Haploinsufficiency of NSD1 causes Sotos syndrome.&lt;/strong&gt; Nature Genet. 30: 365-366, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11896389/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11896389&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng863&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11896389">Kurotaki et al. (2002)</a>, <a href="#33" class="mim-tip-reference" title="Kurotaki, N., Harada, N., Shimokawa, O., Miyake, N., Kawame, H., Uetake, K., Makita, Y., Kondoh, T., Ogata, T., Hasegawa, T., Nagai, T., Ozaki, T., and 22 others. &lt;strong&gt;Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion.&lt;/strong&gt; Hum. Mutat. 22: 378-387, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14517949/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14517949&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.10270&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14517949">Kurotaki et al. (2003)</a> added 70 more cases, 53 of whom were Japanese. Among the 112 total cases, they identified 50 microdeletions (45%) and 16 point mutations (14%). They noted a large difference between Japanese and non-Japanese patients in the frequency of microdeletions, which occurred in 49 (52%) of the 95 Japanese but in only 1 (6%) of the 17 non-Japanese. Most of the microdeletions were confirmed to be identical by FISH analysis. <a href="#33" class="mim-tip-reference" title="Kurotaki, N., Harada, N., Shimokawa, O., Miyake, N., Kawame, H., Uetake, K., Makita, Y., Kondoh, T., Ogata, T., Hasegawa, T., Nagai, T., Ozaki, T., and 22 others. &lt;strong&gt;Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion.&lt;/strong&gt; Hum. Mutat. 22: 378-387, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14517949/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14517949&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.10270&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14517949">Kurotaki et al. (2003)</a> identified highly homologous sequences, i.e., possible low copy repeats, in regions flanking proximal and distal breakpoints of the common deletion. This suggested that low copy repeats may mediate the deletion. The frequency of such low copy repeats seemed to vary in different populations, and thus the differences in frequency of microdeletions between Japanese and non-Japanese cases may have been caused by patient selection bias. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11896389+14517949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Finnish father and son with Sotos syndrome, <a href="#25" class="mim-tip-reference" title="Hoglund, P., Kurotaki, N., Kytola, S., Miyake, N., Somer, M., Matsumoto, N. &lt;strong&gt;Familial Sotos syndrome is caused by a novel 1 bp deletion of the NSD1 gene. (Letter)&lt;/strong&gt; J. Med. Genet. 40: 51-54, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12525543/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12525543&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.40.1.51&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12525543">Hoglund et al. (2003)</a> identified a heterozygous mutation in the NSD1 gene (<a href="/entry/606681#0009">606681.0009</a>). The authors noted that the findings in this family confirm that familial Sotos syndrome is caused by mutation in the NSD1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525543" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Beckwith-Wiedemann syndrome (BWS; <a href="/entry/130650">130650</a>) is, like Sotos syndrome, an overgrowth syndrome. Deregulation of imprinted growth regulatory genes within the 11p15 region is the major cause of BWS. Similarly, defects of the NSD1 gene account for more than 60% of cases of Sotos syndrome. Owing to the clinical overlap between the 2 syndromes, <a href="#3" class="mim-tip-reference" title="Baujat, G., Rio, M., Rossignol, S., Sanlaville, D., Lyonnet, S., Le Merrer, M., Munnich, A., Gicquel, C., Cormier-Daire, V., Colleaux, L. &lt;strong&gt;Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 74: 715-720, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14997421/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14997421&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14997421[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/383093&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14997421">Baujat et al. (2004)</a> investigated whether unexplained cases of Sotos syndrome could be related to 11p15 anomalies and, conversely, whether unexplained BWS cases could be related to NSD1 deletions or mutations. Two 11p15 anomalies were identified in a series of 20 patients with Sotos syndrome, and 2 NSD1 mutations (<a href="/entry/606681#0011">606681.0011</a>-<a href="/entry/606681#0012">606681.0012</a>) were identified in a series of 52 patients with BWS. The results suggested that the 2 disorders may have more similarities than previously thought and that NSD1 could be involved in imprinting of the 11p15 region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14997421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#55" class="mim-tip-reference" title="Turkmen, S., Gillessen-Kaesbach, G., Meinecke, P., Albrecht, B., Neumann, L. M., Hesse, V., Palanduz, S., Balg, S., Majewski, F., Fuchs, S., Zschieschang, P., Greiwe, M., Mennicke, K., Kreuz, F. R., Dehmel, H. J., Rodeck, B., Kunze, J., Tinschert, S., Mundlos, S., Horn, D. &lt;strong&gt;Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.&lt;/strong&gt; Europ. J. Hum. Genet. 11: 858-865, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14571271/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14571271&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5201050&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14571271">Turkmen et al. (2003)</a> screened the NSD1 gene for mutations in 20 patients and 1 familial case with Sotos syndrome, 5 patients with Weaver syndrome, 6 patients with unclassified overgrowth and mental retardation, and 6 patients with macrocephaly and mental retardation. They identified 19 mutations, 17 previously undescribed, in 18 Sotos patients and the familial case (90%). The best correlation between the molecular and clinical findings was for facial gestalt in conjunction with overgrowth, macrocephaly, and developmental delay. <a href="#55" class="mim-tip-reference" title="Turkmen, S., Gillessen-Kaesbach, G., Meinecke, P., Albrecht, B., Neumann, L. M., Hesse, V., Palanduz, S., Balg, S., Majewski, F., Fuchs, S., Zschieschang, P., Greiwe, M., Mennicke, K., Kreuz, F. R., Dehmel, H. J., Rodeck, B., Kunze, J., Tinschert, S., Mundlos, S., Horn, D. &lt;strong&gt;Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.&lt;/strong&gt; Europ. J. Hum. Genet. 11: 858-865, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14571271/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14571271&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5201050&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14571271">Turkmen et al. (2003)</a> found no mutations of the NSD1 gene in the patients with Weaver syndrome or other overgrowth phenotypes and concluded that the great majority of patients with Sotos syndrome have mutations in NSD1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14571271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Douglas, J., Hanks, S., Temple, I. K., Davies, S., Murray, A., Upadhyaya, M., Tomkins, S., Hughes, H. E., Cole, T. R. P., Rahman, N. &lt;strong&gt;NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.&lt;/strong&gt; Am. J. Hum. Genet. 72: 132-143, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12464997/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12464997&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12464997[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/345647&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12464997">Douglas et al. (2003)</a> evaluated 75 patients with childhood overgrowth for intragenic mutations and large deletions in NSD1. Before molecular analyses, the patients were phenotypically scored into 4 groups: 37 patients comprising group 1 had a phenotype typical of Sotos syndrome; 13 patients comprising group 2 had a Sotos-like phenotype but with some atypical features; 7 patients comprising group 3 had been diagnosed with Weaver syndrome (<a href="/entry/277590">277590</a>); and 18 patients comprising group 4 had an overgrowth condition that was neither Sotos nor Weaver syndrome. There was a strong correlation between presence of an NSD1 alteration and clinical phenotype, as 28 of 37 patients (76%) in group 1 had NSD1 mutations or deletions, whereas none of the patients in group 4 had alterations in NSD1. Three of the 7 patients who had been diagnosed with Weaver syndrome had NSD1 mutations (see <a href="/entry/606681#0006">606681.0006</a>). <a href="#53" class="mim-tip-reference" title="Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. &lt;strong&gt;Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.&lt;/strong&gt; Am. J. Hum. Genet. 77: 193-204, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15942875/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15942875&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432082&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15942875">Tatton-Brown et al. (2005)</a> reviewed the phenotype of the 3 patients who carried a diagnosis of Weaver syndrome and in whom <a href="#14" class="mim-tip-reference" title="Douglas, J., Hanks, S., Temple, I. K., Davies, S., Murray, A., Upadhyaya, M., Tomkins, S., Hughes, H. E., Cole, T. R. P., Rahman, N. &lt;strong&gt;NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.&lt;/strong&gt; Am. J. Hum. Genet. 72: 132-143, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12464997/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12464997&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12464997[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/345647&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12464997">Douglas et al. (2003)</a> had identified mutations in the NSD1 gene, and on the basis of multiple pictures at different ages, reclassified 2 of them as having 'typical Sotos syndrome' and the third as 'possible Sotos syndrome.' <a href="#53" class="mim-tip-reference" title="Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. &lt;strong&gt;Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.&lt;/strong&gt; Am. J. Hum. Genet. 77: 193-204, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15942875/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15942875&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432082&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15942875">Tatton-Brown et al. (2005)</a> noted that none of the patients in their series with 'classic' Weaver syndrome had NSD1 mutations, and they concluded that a diagnosis of Weaver syndrome should be given only if the presence of NSD1 abnormalities has been excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15942875+12464997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Kurotaki, N., Stankiewicz, P., Wakui, K., Niikawa, N., Lupski, J. R. &lt;strong&gt;Sotos syndrome common deletion is mediated by directly oriented subunits within inverted Sos-REP low-copy repeats.&lt;/strong&gt; Hum. Molec. Genet. 14: 535-542, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15640245/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15640245&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddi050&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15640245">Kurotaki et al. (2005)</a> characterized 2 complex mosaic low-copy repeats (LCRs) that are centromeric and telomeric to NSD1, which they designated proximal Sos-REP (Sos-PREP, approximately 390 kb) and distal Sos-REP (Sos-DREP, approximately 429 kb), respectively. Among 8 Sotos patients with a common deletion, an approximately 550-kb junction fragment was detected that was generated by nonallelic homologous recombination between Sos-PREP C and Sos-DREP C-prime subunits. This patient-specific junction fragment was not present in 51 Japanese and non-Japanese controls. <a href="#35" class="mim-tip-reference" title="Kurotaki, N., Stankiewicz, P., Wakui, K., Niikawa, N., Lupski, J. R. &lt;strong&gt;Sotos syndrome common deletion is mediated by directly oriented subunits within inverted Sos-REP low-copy repeats.&lt;/strong&gt; Hum. Molec. Genet. 14: 535-542, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15640245/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15640245&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddi050&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15640245">Kurotaki et al. (2005)</a> identified a 2.5-kb unequal crossover hotspot region in 6 of 9 analyzed Sotos patients with the common deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15640245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Douglas, J., Coleman, K., Tatton-Brown, K., Hughes, H. E., Temple, I. K., Cole, T. R. P., Rahman, N., The Childhood Overgrowth Collaboration. &lt;strong&gt;Evaluation of NSD2 and NSD3 in overgrowth syndromes.&lt;/strong&gt; Europ. J. Hum. Genet. 13: 150-153, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15483650/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15483650&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5201298&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15483650">Douglas et al. (2005)</a> did not find truncating mutations or gene deletions in NSD2 (<a href="/entry/602952">602952</a>) and NSD3 (<a href="/entry/607083">607083</a>) in 78 overgrowth syndrome cases in which NSD1 mutations and deletions had been excluded. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15483650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Through analyses of 530 individuals with diverse phenotypes, <a href="#53" class="mim-tip-reference" title="Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. &lt;strong&gt;Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.&lt;/strong&gt; Am. J. Hum. Genet. 77: 193-204, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15942875/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15942875&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432082&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15942875">Tatton-Brown et al. (2005)</a> identified 266 individuals with intragenic NSD1 mutations or 5q35 microdeletions encompassing the NSD1 gene. Of 166 patients with NSD1 abnormalities for whom photographs were available, Sotos syndrome was clinically diagnosed in 164 (99%) independent of the molecular analysis, indicating that NSD1 aberrations are essentially specific to this condition. Analysis of 124 patients from the United Kingdom suggested that 93% of patients who have been clinically diagnosed with Sotos syndrome have identifiable NSD1 abnormalities, of which 83% are intragenic mutations and 10% are 5q35 microdeletions. <a href="#53" class="mim-tip-reference" title="Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. &lt;strong&gt;Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.&lt;/strong&gt; Am. J. Hum. Genet. 77: 193-204, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15942875/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15942875&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/432082&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15942875">Tatton-Brown et al. (2005)</a> identified only 13 familial cases and noted that familial cases were more likely than nonfamilial cases to carry missense mutations (p = 0.005), suggesting that the underlying NSD1 mutation mechanism in Sotos syndrome may influence reproductive fitness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15942875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#56" class="mim-tip-reference" title="van Haelst, M. M., Hoogeboom, J. J. M., Baujat, G., Bruggenwirth, H. T., Van de Laar, I., Coleman, K., Rahman, N., Niermeijer, M. F., Drop, S. L. S., Scambler, P. J. &lt;strong&gt;Familial gigantism caused by an NSD1 mutation.&lt;/strong&gt; Am. J. Med. Genet. 139A: 40-44, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16222665/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16222665&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30973&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16222665">Van Haelst et al. (2005)</a> reported a 3-generation family with gigantism in whom they identified a missense mutation in the NSD1 gene (C2202Y; <a href="/entry/606681#0013">606681.0013</a>). Manifestations in this family included dramatically increased height, weight, and head circumference, long face, large mandible, and large ears. All affected members had normal intelligence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16222665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a female infant with features of both Sotos syndrome and Nevo syndrome (see <a href="/entry/225400">225400</a>), <a href="#31" class="mim-tip-reference" title="Kanemoto, N., Kanemoto, K., Nishimura, G., Kamoda, T., Visser, R., Shimokawa, O., Matsumoto, N. &lt;strong&gt;Nevo syndrome with an NSD1 deletion: a variant of Sotos syndrome?&lt;/strong&gt; Am. J. Med. Genet. 140A: 70-73, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16329110/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16329110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30776&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16329110">Kanemoto et al. (2006)</a> identified heterozygosity for a 2.2-Mb deletion (<a href="/entry/606681#0001">606681.0001</a>) encompassing the NSD1 gene on chromosome 5. The patient was born with flexion contractures of the hands and feet, muscular hypotonia, and hyperbilirubinemia. Her growth was accelerated, but motor and speech development were delayed. At age 17 months, the patient did not speak and had generalized hypotonia, thoracic kyphosis, dolichocephaly, a narrow high-arched palate, large abnormal low-set ears, webbed neck, volar edema, wrist drop, and spindle-shaped fingers. Echocardiography revealed an atrial septal defect and patent ductus arteriosus. Bilateral hydronephrosis was seen by ultrasound, and voiding cystoureterography revealed bilateral vesicoureteral reflux. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16329110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Kaminsky, E. B., Kaul, V., Paschall, J., Church, D. M., Bunke, B., Kunig, D., Moreno-De-Luca, D., Moreno-De-Luca, A., Mulle, J. G., Warren, S. T., Richard, G., Compton, J. G., and 22 others. &lt;strong&gt;An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities.&lt;/strong&gt; Genet. Med. 13: 777-784, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21844811/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21844811&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e31822c79f9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21844811">Kaminsky et al. (2011)</a> presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 5q35 deletion was identified in 8 cases and no controls for a p value of 0.026 and a frequency of 1 in 1,969 cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21844811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
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<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#24" class="mim-tip-reference" title="Hirai, N., Matsune, K., Ohashi, H. &lt;strong&gt;Craniofacial and oral features of Sotos syndrome: differences in patients with submicroscopic deletion and mutation of NSD1 gene.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2933-2939, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22012791/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22012791&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33969&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22012791">Hirai et al. (2011)</a> studied the craniofacial and oral features of 8 Japanese children with Sotos syndrome, including 5 with a submicroscopic deletion at 5q35 and 3 with a mutation in the NSD1 gene. All 8 patients had high palate, excessive tooth wear, and crowding, and all but 1 had hypodontia and deep bite. Hypodontia involved only the second premolars, and there were no differences in the number of missing teeth between patients with the microdeletion or a mutation. Features that were more frequent and more pronounced in patients with the microdeletion included mandibular recession, scissors or posterior crossbite, and small dental arch with labioclination of the maxillary central incisors. Other features seen in a few patients included enamel hypoplasia and ectopic tooth eruption. <a href="#24" class="mim-tip-reference" title="Hirai, N., Matsune, K., Ohashi, H. &lt;strong&gt;Craniofacial and oral features of Sotos syndrome: differences in patients with submicroscopic deletion and mutation of NSD1 gene.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2933-2939, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22012791/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22012791&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33969&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22012791">Hirai et al. (2011)</a> concluded that Sotos syndrome patients should be observed closely for possible dental and oral complications, especially for malocclusion in patients with the microdeletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22012791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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</div>
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</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Boman1980" class="mim-tip-reference" title="Boman, H., Nilsson, D. &lt;strong&gt;Sotos syndrome in two brothers.&lt;/strong&gt; Clin. Genet. 18: 421-427, 1980.">Boman and Nilsson (1980)</a>; <a href="#Dodge1983" class="mim-tip-reference" title="Dodge, P. R., Holmes, S. J., Sotos, J. F. &lt;strong&gt;Cerebral gigantism.&lt;/strong&gt; Dev. Med. Child Neurol. 25: 248-252, 1983.">Dodge et al. (1983)</a>; <a href="#Stephenson1968" class="mim-tip-reference" title="Stephenson, J. N., Mellinger, R. C., Manson, G. &lt;strong&gt;Cerebral gigantism.&lt;/strong&gt; Pediatrics 41: 130-138, 1968.">Stephenson et al.
(1968)</a>
</span>
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<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Allanson1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Allanson, J. E., Cole, T. R. P.
<strong>Sotos syndrome: evolution of facial phenotype subjective and objective assessment.</strong>
Am. J. Med. Genet. 65: 13-20, 1996. Note: Erratum: Am. J. Med. Genet. 79: 229-230, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8914735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8914735</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8914735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19961002)65:1&lt;13::AID-AJMG2&gt;3.0.CO;2-Z" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Bale1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bale, A. E., Drum, M. A., Parry, D. M., Mulvihill, J. J.
<strong>Familial Sotos syndrome (cerebral gigantism): craniofacial and psychological characteristics.</strong>
Am. J. Med. Genet. 20: 613-624, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2581446/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2581446</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2581446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320200407" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Baujat2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Baujat, G., Rio, M., Rossignol, S., Sanlaville, D., Lyonnet, S., Le Merrer, M., Munnich, A., Gicquel, C., Cormier-Daire, V., Colleaux, L.
<strong>Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome.</strong>
Am. J. Hum. Genet. 74: 715-720, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14997421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14997421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14997421[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14997421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/383093" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Bejar1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bejar, R. L., Smith, G. F., Park, S., Spellacy, W. N., Wolfson, S. L., Nyhan, W. L.
<strong>Cerebral gigantism: concentrations of amino acids in plasma and muscle.</strong>
J. Pediat. 76: 105-111, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4312004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4312004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4312004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(70)80138-x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Boman1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Boman, H., Nilsson, D.
<strong>Sotos syndrome in two brothers.</strong>
Clin. Genet. 18: 421-427, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7449180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7449180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7449180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1980.tb01787.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Brown1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, W. T., Wisniewski, K. E., Sudhalter, V., Keogh, M., Tsiouris, J., Miezejeski, C., Schaefer, G. B.
<strong>Identical twins discordant for Sotos syndrome.</strong>
Am. J. Med. Genet. 79: 329-333, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9781916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9781916</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9781916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;329::aid-ajmg17&gt;3.3.co;2-3" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Butler1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Butler, M. G., Meaney, F. J., Kittur, S., Hersh, J. H., Hornstein, L.
<strong>Metacarpophalangeal pattern profile analysis in Sotos syndrome.</strong>
Am. J. Med. Genet. 20: 625-629, 1985. Note: Erratum: Am. J. Med. Genet. 24: 761 only, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3993685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3993685</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=3993685[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3993685" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320200408" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Butler1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Butler, M. G., Meaney, F. J.
<strong>Metacarpophalangeal pattern profile analysis in Sotos syndrome: an update. (Letter)</strong>
Am. J. Med. Genet. 24: 761 only, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3740107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3740107</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3740107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320240421" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="9" class="mim-anchor"></a>
<a id="Cole1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, T. R. P., Hughes, H. E., Jeffreys, M. J., Williams, G. T., Arnold, M. M.
<strong>Small cell lung carcinoma in a patient with Sotos syndrome: are genes at 3p21 involved in both conditions?</strong>
J. Med. Genet. 29: 338-341, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1316442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1316442</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1316442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.29.5.338" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Cole1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, T. R. P., Hughes, H. E.
<strong>Sotos syndrome.</strong>
J. Med. Genet. 27: 571-576, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2231650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2231650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2231650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.27.9.571" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="11" class="mim-anchor"></a>
<a id="Cole1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, T. R. P., Hughes, H. E.
<strong>Sotos syndrome: a study of the diagnostic criteria and natural history.</strong>
J. Med. Genet. 31: 20-32, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7512144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7512144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7512144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.31.1.20" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Dodge1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dodge, P. R., Holmes, S. J., Sotos, J. F.
<strong>Cerebral gigantism.</strong>
Dev. Med. Child Neurol. 25: 248-252, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6602075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6602075</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6602075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1469-8749.1983.tb13750.x" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="13" class="mim-anchor"></a>
<a id="Douglas2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Douglas, J., Coleman, K., Tatton-Brown, K., Hughes, H. E., Temple, I. K., Cole, T. R. P., Rahman, N., The Childhood Overgrowth Collaboration.
<strong>Evaluation of NSD2 and NSD3 in overgrowth syndromes.</strong>
Europ. J. Hum. Genet. 13: 150-153, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15483650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15483650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15483650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/sj.ejhg.5201298" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Douglas2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Douglas, J., Hanks, S., Temple, I. K., Davies, S., Murray, A., Upadhyaya, M., Tomkins, S., Hughes, H. E., Cole, T. R. P., Rahman, N.
<strong>NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.</strong>
Am. J. Hum. Genet. 72: 132-143, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12464997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12464997</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12464997[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12464997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/345647" target="_blank">Full Text</a>]
</p>
</div>
</li>
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<a id="15" class="mim-anchor"></a>
<a id="Faivre2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Faivre, L., Viot, G., Prieur, M., Turleau, C., Gosset, P., Romana, S., Munnich, A., Vekemans, M., Cormier-Daire, V.
<strong>Apparent Sotos syndrome (cerebral gigantism) in a child with Trisomy 20p11.2-p12.1 mosaicism.</strong>
Am. J. Med. Genet. 91: 273-276, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10766982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10766982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10766982" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Fryns1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fryns, J. P.
<strong>The Prader-Willi syndrome and the Sotos syndrome: syndromes or sequences? (Letter)</strong>
Clin. Genet. 33: 457-458, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3168318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3168318</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3168318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1988.tb03481.x" target="_blank">Full Text</a>]
</p>
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<a id="17" class="mim-anchor"></a>
<a id="Fryssira2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fryssira, H., Drossatou, P., Sklavou, R., Barambouti, F., Manolaki, N.
<strong>Two cases of Sotos syndrome with novel mutations of the NSD1 gene.</strong>
Genet. Counsel. 21: 53-59, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20420030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20420030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20420030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Goldstein1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldstein, D. J., Ward, R. E., Moore, E., Fremion, A. S., Wappner, R. S.
<strong>Overgrowth, congenital hypotonia, nystagmus, strabismus, and mental retardation: variant of dominantly inherited Sotos sequence?</strong>
Am. J. Med. Genet. 29: 783-792, 1988.
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[<a href="https://doi.org/10.1002/ajmg.1320290408" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61062" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320120405" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320150125" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1651-2227.1976.tb04902.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33969" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.40.1.51" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(67)80263-4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.10080" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/GIM.0b013e31822c79f9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320260310" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30776" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.33062" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.10270" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng863" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddi050" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1096-8628(20001113)95:2&lt;182::aid-ajmg18&gt;3.0.co;2-8" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archpedi.1984.02140430062016" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320500313" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.1529-8817.2004.00150.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.27.2.130" target="_blank">Full Text</a>]
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<a id="42" class="mim-anchor"></a>
<a id="Noreau1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Noreau, D. R., Al-Ata, J., Jutras, L., Teebi, A. S.
<strong>Congenital heart defects in Sotos syndrome.</strong>
Am. J. Med. Genet. 79: 327-328, 1998.
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;327::aid-ajmg16&gt;3.0.co;2-t" target="_blank">Full Text</a>]
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Opitz, J. M., Weaver, D. W., Reynolds, J. F., Jr.
<strong>The syndromes of Sotos and Weaver: reports and review.</strong>
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[<a href="https://doi.org/10.1002/(sici)1096-8628(19981002)79:4&lt;294::aid-ajmg12&gt;3.0.co;2-m" target="_blank">Full Text</a>]
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<div class="">
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Robertson, S. P., Bankier, A.
<strong>Sotos syndrome and cutis laxa.</strong>
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</p>
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<a id="Ruvalcaba1980" class="mim-anchor"></a>
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<p class="mim-text-font">
Ruvalcaba, R. H. A., Myhre, S., Smith, D. W.
<strong>Sotos syndrome with intestinal polyposis and pigmentary changes of the genitalia.</strong>
Clin. Genet. 18: 413-416, 1980.
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[<a href="https://doi.org/10.1111/j.1399-0004.1980.tb01785.x" target="_blank">Full Text</a>]
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Scarpa, P., Faggioli, R., Voghenzi, A.
<strong>Familial Sotos syndrome: longitudinal study of two additional cases.</strong>
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</p>
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<a id="47" class="mim-anchor"></a>
<a id="Schaefer1997" class="mim-anchor"></a>
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Schaefer, G. B., Bodensteiner, J. B., Buehler, B. A., Lin, A., Cole, T. R. P.
<strong>The neuroimaging findings in Sotos syndrome.</strong>
Am. J. Med. Genet. 68: 462-465, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9021022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9021022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9021022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19970211)68:4&lt;462::aid-ajmg18&gt;3.0.co;2-q" target="_blank">Full Text</a>]
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<a id="Schrander-Stumpel1990" class="mim-anchor"></a>
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Schrander-Stumpel, C. T. R. M., Fryns, J. P., Hamers, G. G.
<strong>Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21)).</strong>
Clin. Genet. 37: 226-229, 1990.
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[<a href="https://doi.org/10.1111/j.1399-0004.1990.tb03507.x" target="_blank">Full Text</a>]
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Smith, A., Farrar, J. R., Silink, M., Judzewitsch, R.
<strong>Investigations in dominant Sotos syndrome.</strong>
Ann. Genet. 24: 226-228, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6977303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6977303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6977303" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Smith1997" class="mim-anchor"></a>
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<p class="mim-text-font">
Smith, M., Fullwood, P., Qi, Y., Palmer, S., Upadhyaya, M., Cole, T.
<strong>No evidence for uniparental disomy as a common cause of Sotos syndrome.</strong>
J. Med. Genet. 34: 10-12, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9032642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9032642</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9032642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.34.1.10" target="_blank">Full Text</a>]
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<a id="Sotos1964" class="mim-anchor"></a>
<div class="">
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Sotos, J. F., Dodge, P. R., Muirhead, D., Crawford, J. D., Talbot, N. B.
<strong>Cerebral gigantism in childhood: a syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder.</strong>
New Eng. J. Med. 271: 109-116, 1964.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14148233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14148233</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14148233" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM196407162710301" target="_blank">Full Text</a>]
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<a id="52" class="mim-anchor"></a>
<a id="Stephenson1968" class="mim-anchor"></a>
<div class="">
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Stephenson, J. N., Mellinger, R. C., Manson, G.
<strong>Cerebral gigantism.</strong>
Pediatrics 41: 130-138, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4169648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4169648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4169648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Tatton-Brown2005" class="mim-anchor"></a>
<div class="">
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Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N.
<strong>Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.</strong>
Am. J. Hum. Genet. 77: 193-204, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15942875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15942875</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15942875[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15942875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/432082" target="_blank">Full Text</a>]
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<a id="Tsukahara1991" class="mim-anchor"></a>
<div class="">
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Tsukahara, M., Kajii, T.
<strong>High resolution-banded chromosomes from patients with Sotos syndrome. (Letter)</strong>
Clin. Genet. 39: 313-314, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2070551/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2070551</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2070551" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1991.tb03034.x" target="_blank">Full Text</a>]
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<a id="Turkmen2003" class="mim-anchor"></a>
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Turkmen, S., Gillessen-Kaesbach, G., Meinecke, P., Albrecht, B., Neumann, L. M., Hesse, V., Palanduz, S., Balg, S., Majewski, F., Fuchs, S., Zschieschang, P., Greiwe, M., Mennicke, K., Kreuz, F. R., Dehmel, H. J., Rodeck, B., Kunze, J., Tinschert, S., Mundlos, S., Horn, D.
<strong>Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.</strong>
Europ. J. Hum. Genet. 11: 858-865, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14571271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14571271</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14571271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/sj.ejhg.5201050" target="_blank">Full Text</a>]
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<a id="van Haelst2005" class="mim-anchor"></a>
<div class="">
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van Haelst, M. M., Hoogeboom, J. J. M., Baujat, G., Bruggenwirth, H. T., Van de Laar, I., Coleman, K., Rahman, N., Niermeijer, M. F., Drop, S. L. S., Scambler, P. J.
<strong>Familial gigantism caused by an NSD1 mutation.</strong>
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[<a href="https://doi.org/10.1002/ajmg.a.30973" target="_blank">Full Text</a>]
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<a id="Winship1985" class="mim-anchor"></a>
<div class="">
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Winship, I. M.
<strong>Sotos syndrome--autosomal dominant inheritance substantiated.</strong>
Clin. Genet. 28: 243-246, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4064361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4064361</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4064361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1985.tb00393.x" target="_blank">Full Text</a>]
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<div class="">
<p class="mim-text-font">
Zonana, J., Rimoin, D. L., Fisher, D. A.
<strong>Cerebral gigantism--apparent dominant inheritance.</strong>
Birth Defects Orig. Art. Ser. XII(6): 63-69, 1976.
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<a id="Zonana1977" class="mim-anchor"></a>
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Zonana, J., Sotos, J. F., Romshe, C. A., Fisher, D. A., Elders, M. J., Rimoin, D. L.
<strong>Dominant inheritance of cerebral gigantism.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/889595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">889595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=889595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(77)80822-6" target="_blank">Full Text</a>]
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Sonja A. Rasmussen - updated : 05/19/2022
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Victor A. McKusick : 6/4/1986
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<strong>#</strong> 117550
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SOTOS SYNDROME; SOTOS
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<em>Alternative titles; symbols</em>
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CEREBRAL GIGANTISM<br />
CHROMOSOME 5q35 DELETION SYNDROME<br />
SOTOS SYNDROME 1, FORMERLY; SOTOS1, FORMERLY
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<strong>SNOMEDCT:</strong> 75968004; &nbsp;
<strong>ICD10CM:</strong> Q87.3; &nbsp;
<strong>ORPHA:</strong> 821; &nbsp;
<strong>DO:</strong> 0112103; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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5q35.3
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Sotos syndrome
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117550
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Autosomal dominant
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3
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NSD1
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606681
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Sotos syndrome (SOTOS) is caused by heterozygous mutation in the NSD1 gene (606681) or by a deletion in the 5q35 region including genomic sequence in addition to the NSD1 gene.</p>
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<strong>Description</strong>
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<p>Sotos syndrome (SOTOS) is a neurologic disorder characterized by overgrowth from the prenatal stage through childhood, with advanced bone age, an unusual face with large skull, acromegalic features and pointed chin, occasional brain anomalies and seizures, and impaired intellectual development (summary by Kurotaki et al., 2002). </p><p>Weaver syndrome (277590), which shows considerable phenotypic overlap with Sotos syndrome, has been shown to be caused by mutation in the EZH2 gene (601573) on chromosome 7q36.</p>
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<strong>Clinical Features</strong>
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<p>Sotos et al. (1964) described 5 children with a disorder characterized by excessively rapid growth, acromegalic features, and a nonprogressive cerebral disorder with mental retardation. High-arched palate and prominent jaw were noted in several of them. Birth length was between the 90th and 97th centiles in all. Bone age was advanced in most. </p><p>Hook and Reynolds (1967) reported that affected children have large hands and feet from birth. Growth is rapid in the first years of life but final height may not be excessive. Bone age is advanced. The skull is large with moderate prognathism. Mild dilation of the cerebral ventricles, nonspecific EEG changes, and seizures have been observed. Poor coordination and mental retardation are features. In 2 patients, Bejar et al. (1970) found abnormal dermatoglyphics, normal growth hormone levels, and high levels of valine, isoleucine and leucine in the blood. The glycine-to-valine ratio seemed particularly useful in distinguishing patients from controls. </p><p>Ruvalcaba et al. (1980) found hamartomatous polyps of the intestine and melanin spots of the penis in 2 males with the Sotos syndrome. Halal (1983) reported that the older of the boys she reported with cerebral gigantism had pigmented spots on the genitalia and that the father had been found to have a rectal polyp--findings like those in the 2 unrelated adult males reported by Ruvalcaba et al. (1980). </p><p>Kaneko et al. (1987) found congenital heart defects in 5 of 10 patients with typical Sotos syndrome. Noreau et al. (1998) found that 3 of 14 Sotos syndrome patients had congenital heart defects. In a literature review, they found another 17 patients with variable cardiac defects, mostly closure defects, making an overall incidence of approximately 8%. </p><p>Goldstein et al. (1988) described 2 unrelated children with macrocephaly, excessive growth, strabismus, hypotonia and developmental delay, and improvement with age. </p><p>In a review, Cole and Hughes (1990) emphasized that the handicaps in Sotos syndrome are fewer than previously believed and tend to improve with age. The latter feature makes identification of affected adults difficult. Cole and Hughes (1994) clinically assessed 79 patients with a provisional diagnosis of Sotos syndrome and evaluated their photographs between ages 1 and 6 years. These photographs, together with photographs of first-degree relatives, also at ages 1 to 6 years, were reviewed by 4 clinical geneticists. In 41 probands, but no first-degree relatives, the facial gestalt was thought to be characteristic of Sotos syndrome. Comparison of anthropometric measurements, bone age, and developmental delay in these 41 probands showed marked differences between them and the remaining 38 probands. Length was identified as the most significantly increased prenatal parameter. In childhood, occipitofrontal head circumference (OFC), height, and weight were all increased. OFC remained above the 97th percentile in all but one case throughout childhood and adulthood, whereas height and weight had a tendency to return toward the mean. This 'normalization' was more pronounced in females and was probably related to their early puberty. Early developmental delay and an advanced bone age were seen in 100% and 84% of cases, respectively. Cole and Hughes (1994) suggested that facial gestalt, growth pattern, bone age, and developmental delay are the major diagnostic criteria. Using these criteria, no affected first-degree relatives were identified. </p><p>Scarpa et al. (1994) described a sister and brother with macrocrania and coarse face (frontal bossing, highly arched palate, prognathism, pointed chin, large ears). Psychomotor development of the sister, who also had advanced osseous maturation, improved significantly at the age of 7 years. Accelerated growth with normal bone age, optic atrophy, renal agenesis with contralateral double kidney, and significant mental retardation (IQ, 45) were shown in the brother at 3.5 years of age. The father of these children was tall, with macrocrania and large hands and feet. He had had learning difficulties in school and was a manual laborer. Scarpa et al. (1994) suggested that these children and their father showed different manifestations of Sotos syndrome. Allanson and Cole (1996) presented anthropometric evaluation of the head in 45 patients with Sotos syndrome between age 1 and 25 years. With increasing age, the face lengthens and the chin becomes more striking. </p><p>Opitz et al. (1998) reported an affected mother and daughter. The mother was described as a large infant and 'as tall as her teacher in school.' Her adult height was 185.4 cm, and she had mandibular prognathism and a prominent pointed chin. The daughter showed a prominent forehead with sparseness of frontal hair and a 'ruddy' or flushed complexion, especially of the nose and perioral area. She had prominent features of the congenital hypotonia/lymphedema sequence with hypermobile joints, especially at the knees and ankles, lymphedema nails (especially toenails), and a high total ridge count (TRC) of the fingertip dermatoglyphics. The mother also had a high TRC and a receding frontal hairline. </p><p>Robertson and Bankier (1999) reported 3 children with anthropometric and dysmorphologic features of classic Sotos syndrome in association with redundant skin folds, joint hypermobility, and, in 2 of the 3, vesicoureteric reflux. Robertson and Bankier (1999) thought the associated features suggested a coexisting connective tissue disorder. All the patients had a normal bone age. Although Sotos syndrome in its classically described form was not present, Robertson and Bankier (1999) concluded that this entity might reflect a related, perhaps allelic, condition. </p><p>Tatton-Brown et al. (2005) reviewed the clinical phenotype of 239 individuals with NSD1 abnormalities and found that facial dysmorphism, learning disability, and childhood overgrowth were present in 90% of individuals; however, both height and head circumference were within the normal range in 10% of individuals, indicating that overgrowth is not obligatory for the diagnosis of Sotos syndrome. A broad spectrum of associated clinical features was also present, the occurrence of which was largely independent of genotype: individuals with identical mutations had different phenotypes, all features present in patients with microdeletions were also observed in patients with mutations, and there was no correlation between deletion size and clinical phenotype. </p><p>Kotilainen et al. (2009) studied the dental manifestations of Sotos syndrome and found that one or more premolar teeth were absent in 9 (69%) of 13 affected children and adolescents. All of the patients with hypodontia had a heterozygous mutation in the NSD1 gene. The patient with the most severe phenotype of tooth agenesis, involving not only the second premolars and third molars but also 1 mandibular incisor, had a microdeletion encompassing the entire NSD1 gene, whereas the 4 patients with the mildest tooth phenotype included both patients with only missense mutations, suggesting that the severity of tooth agenesis might be related to the type of mutation. More than half of the patients had enamel defects or excessive tooth wear. Dental age, based on tooth formation, was within the normal range. </p><p>Fryssira et al. (2010) reported 2 boys with typical features of Sotos syndrome and mutations in the NSD1 gene; 1 patient also had cryptorchidism and vertebral anomalies. The authors noted that despite the wide range of phenotypic features, molecular analysis can correctly identify Sotos syndrome. </p><p>Grand et al. (2019) reported 7 patients with Sotos syndrome with mutations in the NSD1 gene who had hyperinsulinemic hypoglycemia, expanding the phenotypic spectrum of the disorder. The hyperinsulinemic hypoglycemia was persistent beyond a year of life in at least 3 patients; 2 other patients were less than 1 year of age and thus it was not yet known whether it would be persistent. Most of the patients did not have classic features of Sotos syndrome at presentation, with 6 of 7 patients requiring diagnosis by exome sequencing. The authors concluded that NSD1 haploinsufficiency is sufficient to cause hyperinsulinemic hypoglycemia, suggesting a role for NSD1 in glucose hemostasis. They recommended that Sotos syndrome be considered in neonates presenting with hyperinsulinemic hypoglycemia. All patients had some response when treated with diazoxide. </p><p><strong><em>Tumor Formation</em></strong></p><p>
Maldonado et al. (1984) reported the association of malignant tumors in Sotos syndrome. Nance et al. (1990) described a 15-month-old child with Sotos syndrome and a paraspinal neuroblastoma. From this and other evidence, they concluded that children with this disorder may be at an increased risk for developing tumors. Gorlin et al. (1990) estimated a risk of 3.9% of benign or malignant tumors in Sotos syndrome. The same excess of neoplasms is present in other overgrowth syndromes. Le Marec et al. (1999) reported that one of a monozygotic twin pair, both of whom had Sotos syndrome, developed a diffuse gastric carcinoma containing signet ring cells at the age of 26. The young age of occurrence of this gastric carcinoma suggested a genetic factor. Leonard et al. (2000) reported 2 children with Sotos syndrome who had benign sacrococcygeal teratomas. Given that Sotos syndrome and sacrococcygeal teratoma are rare events, the authors suggested that these tumors may be due to the effects of overgrowth on tumor development. </p><p>Two of 7 patients reported by Grand et al. (2019) with SOTOS syndrome with hyperinsulinemic hypoglycemia and mutation in the NSD1 gene had a sacrococcygeal teratoma. </p>
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<strong>Diagnosis</strong>
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<p>Opitz et al. (1998) discussed the differentiation of 2 overgrowth syndromes, Sotos syndrome and Weaver syndrome (277590), and the question of whether the similarities are sufficient to consider them 1 entity. They noted that vertebrate development is constrained into only a very few final or common developmental pathways; therefore, no developmental anomaly seen in humans is unique to ('pathognomonic of') one syndrome. Possible phenotypic differences between the syndromes of Sotos and Weaver pointed out by Opitz et al. (1998) were the following: the Sotos syndrome may be a cancer syndrome, whereas the Weaver syndrome is not (although a neuroblastoma had been reported in the latter disorder). In Sotos syndrome there is remarkably advanced dental maturation; this is rarely commented on in Weaver syndrome. In Weaver syndrome, there are more conspicuous contractures and a facial appearance that experts find convincingly different from that in Sotos syndrome. Opitz et al. (1998) favored allelic heterogeneity as the explanation for the similarities between Sotos and Weaver syndromes. They suggested that mapping and isolation of the causative gene or genes would settle the issue. </p><p>Melchior et al. (2005) developed a denaturing high-performance liquid chromatography (DHPLC) screening protocol for mutation detection in NSD1 that achieved an efficiency of mutation detection comparable to that of direct sequencing. </p><p><strong><em>Differential Diagnosis</em></strong></p><p>
Schaefer et al. (1997) concluded that neuroimaging findings of Sotos syndrome are distinct enough to allow differentiation of this syndrome from other mental retardation syndromes with macrocephaly. The most common abnormality of the cerebral ventricles was prominence of the trigone (90%), followed by prominence of the occipital horns (75%) and ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were increased for age in 70% of the patients and the fluid spaces in the posterior fossa were increased in 70% also. A variety of midline abnormalities were noted but anomalies of the corpus callosum were almost universal. </p>
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<strong>Nomenclature</strong>
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<p>Fryns (1988) referred to cases of the fragile X syndrome (FXS; 300624) in which Sotos syndrome had been diagnosed; he therefore suggested that this disorder be designated the Sotos sequence or the mental retardation-overgrowth sequence. </p>
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<strong>Inheritance</strong>
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<p>Most reported cases of Sotos syndrome have been sporadic and may represent new dominant mutations. Hook and Reynolds (1967) reported a concordant set of affected identical twins. Hooft et al. (1968) described cerebral gigantism in 2 first cousins. Hansen and Friis (1976) described affected mother and child. Zonana et al. (1976) described affected mother and 2 children (male and female). The mother's father may have been affected. Zonana et al. (1977) reported 3 families showing vertical transmission and equal severity in males and females; no male-to-male transmission was observed. As an addendum, they commented on a fourth instance of affected mother and son. Smith et al. (1981) observed affected mother and daughter--the presumed fifth instance of dominant inheritance. The mother had primary hypothyroidism due to Hashimoto disease. Halal (1982) reported a family in which the father and 2 of his sons were affected. She knew of no other instance of documented male-to-male transmission. Winship (1985) described a 'Cape Coloured' family with affected father and 4 children by 2 different, unrelated wives. Presumed Sotos syndrome was described in a mother and 2 daughters by Bale et al. (1985). They suggested that instances of seemingly autosomal recessive inheritance may be examples of incomplete penetrance, gonadal mosaicism, or genetic heterogeneity. Minor changes in 2 mothers of 2 unrelated affected infants reported by Goldstein et al. (1988) suggested dominant inheritance of a Sotos sequence. Brown et al. (1998) described a pair of 5-year-old male monozygotic twins who were discordant for Sotos syndrome. </p><p>The possibility of uniparental disomy in Sotos syndrome was investigated by Smith et al. (1997). Using 112 dinucleotide repeat DNA polymorphisms, they examined parental inheritance of all autosomal pairs, except chromosome 15, in 29 patients with Sotos syndrome. All informative cases showed biparental inheritance and no cases of UPD were found. </p>
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<strong>Heterogeneity</strong>
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<p>In a study of the metacarpophalangeal pattern profile (MCPP) in Sotos syndrome, Butler et al. (1985) found no evidence of heterogeneity and developed a diagnostic tool using MCPP variables, which they suggested may be useful. Butler and Meaney (1986) provided an update on the MCPP. </p>
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<strong>Mapping</strong>
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<p>Schrander-Stumpel et al. (1990) described a 6-year-old boy with Sotos syndrome who also had a de novo, apparently balanced translocation, t(3;6)(p21;p21). They suggested that the autosomal dominant gene for the Sotos syndrome may be located either at 3p21 or 6p21. Tsukahara and Kajii (1991) could find no abnormality in high resolution-banded chromosomes from 5 patients. Involvement of genes at 3p21 was also suggested by the case reported by Cole et al. (1992); a 22-year-old female with Sotos syndrome, a nonsmoker, died of small cell lung carcinoma (182280) for which genetic determinants in the 3p21 region are suggested by loss-of-heterozygosity studies. Maroun et al. (1994) reported the case of a 4-year-old girl with Sotos phenotype and a de novo balanced translocation between 5q and 15q: 46,XX,t(5,15)(q35;q22). They thus suggested 5q35 or 15q22 as the site of an autosomal dominant gene determining Sotos syndrome. </p><p>Faivre et al. (2000) reported a child with apparent Sotos syndrome and mosaicism for partial duplication of the short arm of chromosome 20 (46,XY,dup(20)(p12.1-p11.2)[12]/46,XY[66]). The somatostatin receptor-4 (SSTR4; 182454) gene is located at 20p11.2, encompassed by the duplication. The authors proposed that a dosage effect of this gene might be responsible for some of their patient's clinical findings. </p><p>Imaizumi et al. (2002) described a de novo balanced reciprocal translocation between the long arms of chromosomes 5 and 8, 46,XX,t(5;8)(q35;q24.1), in a 15-month-old girl with a typical Sotos syndrome phenotype. They proposed that a gene responsible for this disorder is located in the distal long arm region of chromosome 5. </p>
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<strong>Molecular Genetics</strong>
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<p>In patients with Sotos syndrome harboring a chromosomal translocation, Kurotaki et al. (2002) isolated the NSD1 (606681) gene from the 5q35 breakpoint. They identified 1 nonsense, 3 frameshift, and 20 submicroscopic deletion mutations of NSD1 among 42 sporadic cases of Sotos syndrome. The results indicated that haploinsufficiency of NSD1 is the major cause of Sotos syndrome. </p><p>To the 42 cases of Sotos syndrome reported by Kurotaki et al. (2002), Kurotaki et al. (2003) added 70 more cases, 53 of whom were Japanese. Among the 112 total cases, they identified 50 microdeletions (45%) and 16 point mutations (14%). They noted a large difference between Japanese and non-Japanese patients in the frequency of microdeletions, which occurred in 49 (52%) of the 95 Japanese but in only 1 (6%) of the 17 non-Japanese. Most of the microdeletions were confirmed to be identical by FISH analysis. Kurotaki et al. (2003) identified highly homologous sequences, i.e., possible low copy repeats, in regions flanking proximal and distal breakpoints of the common deletion. This suggested that low copy repeats may mediate the deletion. The frequency of such low copy repeats seemed to vary in different populations, and thus the differences in frequency of microdeletions between Japanese and non-Japanese cases may have been caused by patient selection bias. </p><p>In a Finnish father and son with Sotos syndrome, Hoglund et al. (2003) identified a heterozygous mutation in the NSD1 gene (606681.0009). The authors noted that the findings in this family confirm that familial Sotos syndrome is caused by mutation in the NSD1 gene. </p><p>Beckwith-Wiedemann syndrome (BWS; 130650) is, like Sotos syndrome, an overgrowth syndrome. Deregulation of imprinted growth regulatory genes within the 11p15 region is the major cause of BWS. Similarly, defects of the NSD1 gene account for more than 60% of cases of Sotos syndrome. Owing to the clinical overlap between the 2 syndromes, Baujat et al. (2004) investigated whether unexplained cases of Sotos syndrome could be related to 11p15 anomalies and, conversely, whether unexplained BWS cases could be related to NSD1 deletions or mutations. Two 11p15 anomalies were identified in a series of 20 patients with Sotos syndrome, and 2 NSD1 mutations (606681.0011-606681.0012) were identified in a series of 52 patients with BWS. The results suggested that the 2 disorders may have more similarities than previously thought and that NSD1 could be involved in imprinting of the 11p15 region. </p><p>Turkmen et al. (2003) screened the NSD1 gene for mutations in 20 patients and 1 familial case with Sotos syndrome, 5 patients with Weaver syndrome, 6 patients with unclassified overgrowth and mental retardation, and 6 patients with macrocephaly and mental retardation. They identified 19 mutations, 17 previously undescribed, in 18 Sotos patients and the familial case (90%). The best correlation between the molecular and clinical findings was for facial gestalt in conjunction with overgrowth, macrocephaly, and developmental delay. Turkmen et al. (2003) found no mutations of the NSD1 gene in the patients with Weaver syndrome or other overgrowth phenotypes and concluded that the great majority of patients with Sotos syndrome have mutations in NSD1. </p><p>Douglas et al. (2003) evaluated 75 patients with childhood overgrowth for intragenic mutations and large deletions in NSD1. Before molecular analyses, the patients were phenotypically scored into 4 groups: 37 patients comprising group 1 had a phenotype typical of Sotos syndrome; 13 patients comprising group 2 had a Sotos-like phenotype but with some atypical features; 7 patients comprising group 3 had been diagnosed with Weaver syndrome (277590); and 18 patients comprising group 4 had an overgrowth condition that was neither Sotos nor Weaver syndrome. There was a strong correlation between presence of an NSD1 alteration and clinical phenotype, as 28 of 37 patients (76%) in group 1 had NSD1 mutations or deletions, whereas none of the patients in group 4 had alterations in NSD1. Three of the 7 patients who had been diagnosed with Weaver syndrome had NSD1 mutations (see 606681.0006). Tatton-Brown et al. (2005) reviewed the phenotype of the 3 patients who carried a diagnosis of Weaver syndrome and in whom Douglas et al. (2003) had identified mutations in the NSD1 gene, and on the basis of multiple pictures at different ages, reclassified 2 of them as having 'typical Sotos syndrome' and the third as 'possible Sotos syndrome.' Tatton-Brown et al. (2005) noted that none of the patients in their series with 'classic' Weaver syndrome had NSD1 mutations, and they concluded that a diagnosis of Weaver syndrome should be given only if the presence of NSD1 abnormalities has been excluded. </p><p>Kurotaki et al. (2005) characterized 2 complex mosaic low-copy repeats (LCRs) that are centromeric and telomeric to NSD1, which they designated proximal Sos-REP (Sos-PREP, approximately 390 kb) and distal Sos-REP (Sos-DREP, approximately 429 kb), respectively. Among 8 Sotos patients with a common deletion, an approximately 550-kb junction fragment was detected that was generated by nonallelic homologous recombination between Sos-PREP C and Sos-DREP C-prime subunits. This patient-specific junction fragment was not present in 51 Japanese and non-Japanese controls. Kurotaki et al. (2005) identified a 2.5-kb unequal crossover hotspot region in 6 of 9 analyzed Sotos patients with the common deletion. </p><p>Douglas et al. (2005) did not find truncating mutations or gene deletions in NSD2 (602952) and NSD3 (607083) in 78 overgrowth syndrome cases in which NSD1 mutations and deletions had been excluded. </p><p>Through analyses of 530 individuals with diverse phenotypes, Tatton-Brown et al. (2005) identified 266 individuals with intragenic NSD1 mutations or 5q35 microdeletions encompassing the NSD1 gene. Of 166 patients with NSD1 abnormalities for whom photographs were available, Sotos syndrome was clinically diagnosed in 164 (99%) independent of the molecular analysis, indicating that NSD1 aberrations are essentially specific to this condition. Analysis of 124 patients from the United Kingdom suggested that 93% of patients who have been clinically diagnosed with Sotos syndrome have identifiable NSD1 abnormalities, of which 83% are intragenic mutations and 10% are 5q35 microdeletions. Tatton-Brown et al. (2005) identified only 13 familial cases and noted that familial cases were more likely than nonfamilial cases to carry missense mutations (p = 0.005), suggesting that the underlying NSD1 mutation mechanism in Sotos syndrome may influence reproductive fitness. </p><p>Van Haelst et al. (2005) reported a 3-generation family with gigantism in whom they identified a missense mutation in the NSD1 gene (C2202Y; 606681.0013). Manifestations in this family included dramatically increased height, weight, and head circumference, long face, large mandible, and large ears. All affected members had normal intelligence. </p><p>In a female infant with features of both Sotos syndrome and Nevo syndrome (see 225400), Kanemoto et al. (2006) identified heterozygosity for a 2.2-Mb deletion (606681.0001) encompassing the NSD1 gene on chromosome 5. The patient was born with flexion contractures of the hands and feet, muscular hypotonia, and hyperbilirubinemia. Her growth was accelerated, but motor and speech development were delayed. At age 17 months, the patient did not speak and had generalized hypotonia, thoracic kyphosis, dolichocephaly, a narrow high-arched palate, large abnormal low-set ears, webbed neck, volar edema, wrist drop, and spindle-shaped fingers. Echocardiography revealed an atrial septal defect and patent ductus arteriosus. Bilateral hydronephrosis was seen by ultrasound, and voiding cystoureterography revealed bilateral vesicoureteral reflux. </p><p>Kaminsky et al. (2011) presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 5q35 deletion was identified in 8 cases and no controls for a p value of 0.026 and a frequency of 1 in 1,969 cases. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Hirai et al. (2011) studied the craniofacial and oral features of 8 Japanese children with Sotos syndrome, including 5 with a submicroscopic deletion at 5q35 and 3 with a mutation in the NSD1 gene. All 8 patients had high palate, excessive tooth wear, and crowding, and all but 1 had hypodontia and deep bite. Hypodontia involved only the second premolars, and there were no differences in the number of missing teeth between patients with the microdeletion or a mutation. Features that were more frequent and more pronounced in patients with the microdeletion included mandibular recession, scissors or posterior crossbite, and small dental arch with labioclination of the maxillary central incisors. Other features seen in a few patients included enamel hypoplasia and ectopic tooth eruption. Hirai et al. (2011) concluded that Sotos syndrome patients should be observed closely for possible dental and oral complications, especially for malocclusion in patients with the microdeletion. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Boman and Nilsson (1980); Dodge et al. (1983); Stephenson et al.
(1968)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
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<p class="mim-text-font">
Schrander-Stumpel, C. T. R. M., Fryns, J. P., Hamers, G. G.
<strong>Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21)).</strong>
Clin. Genet. 37: 226-229, 1990.
[PubMed: 2323093]
[Full Text: https://doi.org/10.1111/j.1399-0004.1990.tb03507.x]
</p>
</li>
<li>
<p class="mim-text-font">
Smith, A., Farrar, J. R., Silink, M., Judzewitsch, R.
<strong>Investigations in dominant Sotos syndrome.</strong>
Ann. Genet. 24: 226-228, 1981.
[PubMed: 6977303]
</p>
</li>
<li>
<p class="mim-text-font">
Smith, M., Fullwood, P., Qi, Y., Palmer, S., Upadhyaya, M., Cole, T.
<strong>No evidence for uniparental disomy as a common cause of Sotos syndrome.</strong>
J. Med. Genet. 34: 10-12, 1997.
[PubMed: 9032642]
[Full Text: https://doi.org/10.1136/jmg.34.1.10]
</p>
</li>
<li>
<p class="mim-text-font">
Sotos, J. F., Dodge, P. R., Muirhead, D., Crawford, J. D., Talbot, N. B.
<strong>Cerebral gigantism in childhood: a syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder.</strong>
New Eng. J. Med. 271: 109-116, 1964.
[PubMed: 14148233]
[Full Text: https://doi.org/10.1056/NEJM196407162710301]
</p>
</li>
<li>
<p class="mim-text-font">
Stephenson, J. N., Mellinger, R. C., Manson, G.
<strong>Cerebral gigantism.</strong>
Pediatrics 41: 130-138, 1968.
[PubMed: 4169648]
</p>
</li>
<li>
<p class="mim-text-font">
Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T. R. P., Das, S., Horn, D., Hughes, H. E., Temple, I. K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N.
<strong>Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations.</strong>
Am. J. Hum. Genet. 77: 193-204, 2005.
[PubMed: 15942875]
[Full Text: https://doi.org/10.1086/432082]
</p>
</li>
<li>
<p class="mim-text-font">
Tsukahara, M., Kajii, T.
<strong>High resolution-banded chromosomes from patients with Sotos syndrome. (Letter)</strong>
Clin. Genet. 39: 313-314, 1991.
[PubMed: 2070551]
[Full Text: https://doi.org/10.1111/j.1399-0004.1991.tb03034.x]
</p>
</li>
<li>
<p class="mim-text-font">
Turkmen, S., Gillessen-Kaesbach, G., Meinecke, P., Albrecht, B., Neumann, L. M., Hesse, V., Palanduz, S., Balg, S., Majewski, F., Fuchs, S., Zschieschang, P., Greiwe, M., Mennicke, K., Kreuz, F. R., Dehmel, H. J., Rodeck, B., Kunze, J., Tinschert, S., Mundlos, S., Horn, D.
<strong>Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes.</strong>
Europ. J. Hum. Genet. 11: 858-865, 2003.
[PubMed: 14571271]
[Full Text: https://doi.org/10.1038/sj.ejhg.5201050]
</p>
</li>
<li>
<p class="mim-text-font">
van Haelst, M. M., Hoogeboom, J. J. M., Baujat, G., Bruggenwirth, H. T., Van de Laar, I., Coleman, K., Rahman, N., Niermeijer, M. F., Drop, S. L. S., Scambler, P. J.
<strong>Familial gigantism caused by an NSD1 mutation.</strong>
Am. J. Med. Genet. 139A: 40-44, 2005.
[PubMed: 16222665]
[Full Text: https://doi.org/10.1002/ajmg.a.30973]
</p>
</li>
<li>
<p class="mim-text-font">
Winship, I. M.
<strong>Sotos syndrome--autosomal dominant inheritance substantiated.</strong>
Clin. Genet. 28: 243-246, 1985.
[PubMed: 4064361]
[Full Text: https://doi.org/10.1111/j.1399-0004.1985.tb00393.x]
</p>
</li>
<li>
<p class="mim-text-font">
Zonana, J., Rimoin, D. L., Fisher, D. A.
<strong>Cerebral gigantism--apparent dominant inheritance.</strong>
Birth Defects Orig. Art. Ser. XII(6): 63-69, 1976.
</p>
</li>
<li>
<p class="mim-text-font">
Zonana, J., Sotos, J. F., Romshe, C. A., Fisher, D. A., Elders, M. J., Rimoin, D. L.
<strong>Dominant inheritance of cerebral gigantism.</strong>
J. Pediat. 91: 251-256, 1977.
[PubMed: 889595]
[Full Text: https://doi.org/10.1016/s0022-3476(77)80822-6]
</p>
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Sonja A. Rasmussen - updated : 05/19/2022<br>Marla J. F. O&#x27;Neill - updated : 9/25/2015<br>Marla J. F. O&#x27;Neill - updated : 5/2/2013<br>Marla J. F. O&#x27;Neill - updated : 2/21/2013<br>Ada Hamosh - updated : 10/4/2012<br>Marla J. F. O&#x27;Neill - updated : 6/10/2010<br>George E. Tiller - updated : 1/3/2008<br>Marla J. F. O&#x27;Neill - updated : 1/25/2006<br>Marla J. F. O&#x27;Neill - updated : 11/17/2005<br>Marla J. F. O&#x27;Neill - updated : 8/30/2005<br>Victor A. McKusick - updated : 5/12/2005<br>Victor A. McKusick - updated : 4/20/2005<br>Marla J. F. O&#x27;Neill - updated : 5/14/2004<br>Victor A. McKusick - updated : 4/21/2004<br>Cassandra L. Kniffin - updated : 12/9/2003<br>Victor A. McKusick - updated : 11/19/2003<br>Cassandra L. Kniffin - reorganized : 4/16/2002<br>Ada Hamosh - updated : 3/28/2002<br>Victor A. McKusick - updated : 1/17/2002<br>Victor A. McKusick - updated : 4/12/2001<br>Sonja A. Rasmussen - updated : 11/27/2000<br>Sonja A. Rasmussen - updated : 9/15/2000<br>Wilson H. Y. Lo - updated : 2/10/2000<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 4/1/1997<br>Iosif W. Lurie - updated : 7/15/1996
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Victor A. McKusick : 6/4/1986
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