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Entry
- #610733 - NOONAN SYNDROME 4; NS4
- OMIM
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<span class="h4">#610733</span>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/610733"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS163950"> <strong>Phenotypic Series</strong> </a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<div><a href="https://clinicaltrials.gov/search?cond=NOONAN 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><a href="https://wormbase.org/resources/disease/DOID:0060582" 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>
</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>ORPHA:</strong> 648<br />
<strong>DO:</strong> 0060582<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>
610733
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
NOONAN SYNDROME 4; NS4
</span>
</h3>
</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/2/200?start=-3&limit=10&highlight=200">
2p22.1
</a>
</span>
</td>
<td>
<span class="mim-font">
Noonan syndrome 4
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610733"> 610733 </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">
SOS1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182530"> 182530 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/610733" 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">
<a href="/phenotypicSeries/PS163950" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', '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/610733" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/610733" 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">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</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 />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low-set posteriorly rotated ears <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857486&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857486</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000368" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000368</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">
- Sparse eyebrows <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422441003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422441003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578682</a>, <a href="https://bioportal.bioontology.org/search?q=C1832446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1832446</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002223" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002223</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span><br /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
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 /> -
Epicanthal folds <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74824007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74824007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678230</a>, <a href="https://bioportal.bioontology.org/search?q=C0229249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0229249</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span><br /> -
Blue eyes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301952009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301952009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578626&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578626</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000635</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000635</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Flat nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17&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> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thick lips <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836543</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Dental malocclusion <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/707598004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">707598004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/47944004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">47944004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000689</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000689</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Webbed neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11731003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11731003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q18.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q18.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/744.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">744.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221217&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221217</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000465" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000465</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000465" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000465</a>]</span><br /> -
Short neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95427009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95427009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Neck,Short-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531&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>
<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">
- Congenital heart defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13213009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13213009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q24.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span><br /> -
Hypertrophic cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195020003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195020003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>, <a href="https://bioportal.bioontology.org/search?q=C0340425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340425</a>, <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span><br /> -
Ventricular septal defects <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 /> -
Pulmonic stenosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56786000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56786000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1956257&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1956257</a>, <a href="https://bioportal.bioontology.org/search?q=C0034089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001642</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001642</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pectus excavatum inferiorly <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864796&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864796</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000915" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000915</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000915" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000915</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Breasts </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Widely spaced nipples <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/423230008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">423230008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1827524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1827524</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006610" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006610</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006610" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006610</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cryptorchidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204878001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010417</a>, <a href="https://bioportal.bioontology.org/search?q=C5441920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cubitus valgus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54583007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54583007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70123009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70123009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265611</a>, <a href="https://bioportal.bioontology.org/search?q=C0158465&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158465</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002967" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002967</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002967" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002967</a>]</span><br /> -
Blunt fingertips <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834130&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834130</a>]</span><br /> -
Polyarticular villonodular synovitis in knees, ankles, wrists, and/or elbows (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808060&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808060</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Ectodermal symptoms <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552354</a>]</span><br /> -
Keratosis pilaris <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5132005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5132005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0263383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0263383</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032152</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032152" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032152</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">
- High anterior hairline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276036&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276036</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009890" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009890</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009890" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009890</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Hairline,High_Anterior-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=1ed202dc7ca7d5b2c5e34a787d713dec&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Curly hair <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/225570000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">225570000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0558165&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0558165</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002212" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002212</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002212" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002212</a>]</span><br /> -
Sparse eyebrows <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422441003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422441003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578682</a>, <a href="https://bioportal.bioontology.org/search?q=C1832446&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1832446</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002223" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002223</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0045075" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0045075</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">
- Mild cognitive impairment (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386805003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386805003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G31.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G31.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1270972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1270972</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Prolonged bleeding time (less common) <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R79.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R79.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151529&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151529</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003010</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003010" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003010</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEOPLASIA </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Multiple giant cell granulomas (bones, joints, soft tissues) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1969540&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1969540</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Partial deficiency of factor XI (less common) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552351&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552351</a>]</span><br /> -
Partial deficiency of factor XIII (less common) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3552352&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3552352</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the SOS Ras/Rac guanine nucleotide exchange factor 1 gene (SOS1, <a href="/entry/182530#0002">182530.0002</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Noonan syndrome
- <a href="/phenotypicSeries/PS163950">PS163950</a>
- 16 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/943?start=-3&limit=10&highlight=943"> 1p13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613224"> Noonan syndrome 6 </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">
<a href="/entry/613224"> 613224 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164790"> NRAS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164790"> 164790 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1231?start=-3&limit=10&highlight=1231"> 1q22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615355"> Noonan syndrome 8 </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">
<a href="/entry/615355"> 615355 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609591"> RIT1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609591"> 609591 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/151?start=-3&limit=10&highlight=151"> 2p23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617506"> Noonan syndrome-like disorder with loose anagen hair 2 </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">
<a href="/entry/617506"> 617506 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600590"> PPP1CB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600590"> 600590 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/200?start=-3&limit=10&highlight=200"> 2p22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610733"> Noonan syndrome 4 </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">
<a href="/entry/610733"> 610733 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182530"> SOS1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182530"> 182530 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/304?start=-3&limit=10&highlight=304"> 2p14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619745"> Noonan syndrome 14 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
<a href="/entry/619745"> 619745 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609292"> SPRED2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609292"> 609292 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/70?start=-3&limit=10&highlight=70"> 3p25.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611553"> Noonan syndrome 5 </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">
<a href="/entry/611553"> 611553 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164760"> RAF1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164760"> 164760 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/718?start=-3&limit=10&highlight=718"> 3q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618499"> Noonan syndrome 11 </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">
<a href="/entry/618499"> 618499 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608435"> MRAS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608435"> 608435 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/742?start=-3&limit=10&highlight=742"> 7q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613706"> Noonan syndrome 7 </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">
<a href="/entry/613706"> 613706 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164757"> BRAF </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164757"> 164757 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/563?start=-3&limit=10&highlight=563"> 10q25.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607721"> Noonan syndrome-like with loose anagen hair 1 </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">
<a href="/entry/607721"> 607721 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602775"> SHOC2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602775"> 602775 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/193?start=-3&limit=10&highlight=193"> 11p15.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618624"> Noonan syndrome 12 </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">
<a href="/entry/618624"> 618624 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600098"> RRAS2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600098"> 600098 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/240?start=-3&limit=10&highlight=240"> 12p12.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609942"> Noonan syndrome 3 </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">
<a href="/entry/609942"> 609942 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/190070"> KRAS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/190070"> 190070 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/823?start=-3&limit=10&highlight=823"> 12q24.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/163950"> Noonan syndrome 1 </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">
<a href="/entry/163950"> 163950 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176876"> PTPN11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/176876"> 176876 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/218?start=-3&limit=10&highlight=218"> 14q21.3 </a>
</span>
</td>
<td>
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<a href="/entry/616559"> Noonan syndrome 9 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
<a href="/entry/616559"> 616559 </a>
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<a href="/entry/601247"> SOS2 </a>
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<span class="mim-font">
<a href="/entry/601247"> 601247 </a>
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<a href="/geneMap/22/71?start=-3&limit=10&highlight=71"> 22q11.21 </a>
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<span class="mim-font">
<a href="/entry/616564"> Noonan syndrome 10 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
<a href="/entry/616564"> 616564 </a>
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<a href="/entry/600574"> LZTR1 </a>
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<span class="mim-font">
<a href="/entry/600574"> 600574 </a>
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<span class="mim-font">
<a href="/geneMap/22/71?start=-3&limit=10&highlight=71"> 22q11.21 </a>
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<span class="mim-font">
<a href="/entry/605275"> Noonan syndrome 2 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
<a href="/entry/605275"> 605275 </a>
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<span class="mim-font">
<a href="/entry/600574"> LZTR1 </a>
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<span class="mim-font">
<a href="/entry/600574"> 600574 </a>
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<span class="mim-font">
<a href="/geneMap/22/85?start=-3&limit=10&highlight=85"> 22q11.22 </a>
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<span class="mim-font">
<a href="/entry/619087"> Noonan syndrome 13 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
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<span class="mim-font">
<a href="/entry/619087"> 619087 </a>
</span>
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<span class="mim-font">
<a href="/entry/176948"> MAPK1 </a>
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<span class="mim-font">
<a href="/entry/176948"> 176948 </a>
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<p>A number sign (#) is used with this entry because of evidence that Noonan syndrome-4 (NS4) is caused by heterozygous mutation in the SOS1 gene (<a href="/entry/182530">182530</a>) on chromosome 2p22.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (<a href="/entry/163950">163950</a>).</p>
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<strong>Description</strong>
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<p>Noonan syndrome-4 (NS4) is an autosomal dominant disorder characterized by a variable phenotype comprising short stature, congenital heart defects, and facial dysmorphisms (summary by <a href="#1" class="mim-tip-reference" title="Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C. &lt;strong&gt;Clinical and molecular characterization of 40 patients with Noonan syndrome.&lt;/strong&gt; Europ. J. Med. Genet. 51: 566-572, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18678287/&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;18678287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2008.06.011&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="18678287">Ferrero et al., 2008</a>). Patients often have ectodermal anomalies, such as keratitis pilaris, curly hair, and ocular ptosis (<a href="#5" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. &lt;strong&gt;Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143282/&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;17143282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1939&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="17143282">Tartaglia et al., 2007</a>; <a href="#8" class="mim-tip-reference" title="Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others. &lt;strong&gt;SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)&lt;/strong&gt; J. Med. Genet. 44: 651-656, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17586837/&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;17586837&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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/10.1136/jmg.2007.051276&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="17586837">Zenker et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143282+17586837+18678287" 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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<strong>Clinical Features</strong>
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<p><a href="#4" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. &lt;strong&gt;Germline gain-of-function mutations in SOS1 cause Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 70-74, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143285/&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;17143285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1926&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="17143285">Roberts et al. (2007)</a> and <a href="#5" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. &lt;strong&gt;Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143282/&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;17143282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1939&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="17143282">Tartaglia et al. (2007)</a> delineated a Noonan syndrome phenotype caused by mutation in the SOS1 gene that lies within the Noonan syndrome spectrum but is distinctive. <a href="#4" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. &lt;strong&gt;Germline gain-of-function mutations in SOS1 cause Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 70-74, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143285/&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;17143285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1926&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="17143285">Roberts et al. (2007)</a> noted 2 significant differences: pulmonic stenosis was more frequent in patients with SOS1 mutations than in those without SOS1 or PTPN11 mutations, and atrial septal defect was relatively rare in affected individuals with SOS1 mutations compared to those with PTPN11 mutations. <a href="#5" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. &lt;strong&gt;Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143282/&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;17143282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1939&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="17143282">Tartaglia et al. (2007)</a> noted ectodermal features including keratosis pilaris and curly hair that were significantly more prevalent among individuals with an SOS1 mutation compared with the general Noonan population. They observed height below the third percentile in only 2 of 15 individuals with an SOS1 mutation, whereas the prevalence is approximately 70% among patients with Noonan syndrome in general and among those with a PTPN11 mutation. In contrast, macrocephaly was overrepresented among those with SOS1 mutations. Only one individual with an SOS1 mutation had mental retardation, potentially attributable to critical illness as a newborn. In comparison, 30% of all children with Noonan syndrome require special education. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143282+17143285" 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="#8" class="mim-tip-reference" title="Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others. &lt;strong&gt;SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)&lt;/strong&gt; J. Med. Genet. 44: 651-656, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17586837/&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;17586837&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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/10.1136/jmg.2007.051276&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="17586837">Zenker et al. (2007)</a> reported that Noonan syndrome patients with SOS1 mutations commonly had ectodermal manifestations including keratosis pilaris of the face, sparse eyebrows, curly hair, and, in 1 patient, ichthyosiform skin changes. By comparing clinical features of a cohort of 42 patients with PTPN11 mutations derived from a previous study with those of their current study of 28 patients with SOS1 mutations, <a href="#8" class="mim-tip-reference" title="Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others. &lt;strong&gt;SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)&lt;/strong&gt; J. Med. Genet. 44: 651-656, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17586837/&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;17586837&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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/10.1136/jmg.2007.051276&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="17586837">Zenker et al. (2007)</a> confirmed a significantly higher prevalence of keratosis pilaris/hyperkeratotic skin and curly hair in patients with SOS1 mutations compared with those with PTP11 alterations (58% vs 6% and 78% vs 34%, respectively). Moreover, ocular ptosis was observed more frequently in patients with NS with SOS1 mutations than in patients with a PTPN11 mutation (80% vs 54%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17586837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C. &lt;strong&gt;Clinical and molecular characterization of 40 patients with Noonan syndrome.&lt;/strong&gt; Europ. J. Med. Genet. 51: 566-572, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18678287/&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;18678287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2008.06.011&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="18678287">Ferrero et al. (2008)</a> reported a newborn with Noonan syndrome due to SOS1 mutation (T266K; <a href="/entry/182530#0002">182530.0002</a>). He presented with facial dysmorphisms and prenatal anomalies, not associated with other congenital defects. The pregnancy was characterized by polyhydramnios and increased fetal nuchal translucency. Dysmorphic facial features included hypertelorism, epicanthal folds, flat nasal bridge, low-set posteriorly rotated ears, and short neck. Other features included moderated pulmonic stenosis and bilateral cryptorchidism. Developmental milestones were normal at 24 months of age. There were no coagulation abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678287" 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="#6" class="mim-tip-reference" title="van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I. &lt;strong&gt;Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.&lt;/strong&gt; Am. J. Med. Genet. 173A: 2968-2972, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28884940/&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;28884940&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.38466&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="28884940">Van Trier et al. (2017)</a> reported 10 members of a 3-generation family with NS4. The patients, who ranged in age from 8 to 73 years, had variable phenotypic expression, ranging from almost no clinical characteristics to a typical presentation. Three family members had suggestive facial characteristics of NS4, whereas 2 had typical facial features. Four patients had pectus excavatum. Seven patients had ptosis and 6 had sparse eyebrows. One patient had intellectual delay and 5 had motor delays. Two had sensorineural hearing loss. None of the patients had short stature, lymphatic dysplasia, cryptorchidism, skin findings, or congenital heart disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28884940" 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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<p><a href="#3" class="mim-tip-reference" title="Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G. &lt;strong&gt;Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 146A: 2966-2967, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18925667/&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;18925667&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32538&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="18925667">Mascheroni et al. (2008)</a> reported a girl with NS4 who presented at age 13 years with swelling and severe pain in her right foot and ankle, which was found to result from pigmented villonodular synovitis (PVNS). Histologically, the synovia was hyperplastic, with villi covered by reactive-appearing synovial cells in multiple layers and histio-fibroblastic and capillary proliferation. History revealed that she had congenital pulmonary valve stenosis and ventricular septal defect, and a coagulopathy with partial factor VIII and XI deficiencies. Physical examination showed short stature, curly hair, sparse eyebrows, hypertelorism, flat nasal bridge, epicanthal folds, prominent pale blue eyes, bilateral ptosis, thick lips, low-set retroverted ears with thickened helices, facial keratosis pilaris, wide-spaced nipples, pectus excavatum, and scoliosis. Psychomotor and cognitive development was normal. <a href="#3" class="mim-tip-reference" title="Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G. &lt;strong&gt;Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 146A: 2966-2967, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18925667/&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;18925667&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32538&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="18925667">Mascheroni et al. (2008)</a> suggested that PVNS is a proliferative lesion that can be part of the phenotypic spectrum of Noonan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H. &lt;strong&gt;SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.&lt;/strong&gt; Clin. Genet. 75: 568-571, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19438935/&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;19438935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2009.01149.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="19438935">Hanna et al. (2009)</a> reported 2 brothers, born of consanguineous parents, with Noonan syndrome-like disorder with multiple giant cell lesions. One boy presented at age 4.5 years with a 2-year history of bilateral progressive swelling of the mandible. A preliminary diagnosis of cherubism (<a href="/entry/118400">118400</a>) was considered. Radiographic studies showed multilocular lesions of the mandibular rami, consistent with giant cell lesions. The boy's 6.5-year-old brother presented with severe pulmonary valvular stenosis and was found to have similar multilocular lesions of the mandible as his brother. Both boys had characteristic facial features of Noonan syndrome, including high anterior hairline with frontal bossing, follicular hyperkeratosis of the forehead (keratosis pilaris), depressed nasal bridge, hypertelorism, downslanting palpebral fissures, and low-set and posteriorly angulated ears with thick helices. Other features included short neck and widely spaced nipples. Both showed normal development and normal stature. The father showed milder features of the disorder, with long face, downslanting palpebral fissures, low-set ears, and widely spaced nipples. Molecular studies identified a heterozygous mutation in the SOS1 gene (W432R; <a href="/entry/182530#0006">182530.0006</a>) in all 3 individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19438935" 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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<p><a href="#4" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. &lt;strong&gt;Germline gain-of-function mutations in SOS1 cause Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 70-74, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143285/&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;17143285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1926&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="17143285">Roberts et al. (2007)</a> and <a href="#5" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. &lt;strong&gt;Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143282/&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;17143282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1939&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="17143282">Tartaglia et al. (2007)</a> found mutation in the SOS1 gene (<a href="/entry/182530">182530</a>) in Noonan syndrome patients without mutation in PTPN11 (<a href="/entry/176876">176876</a>) or KRAS2 (<a href="/entry/190070">190070</a>). Gain-of-function mutations in PTPN11, which encodes the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases, and less than 5% of cases are caused by mutations in KRAS2. SHP2 is required for RAS-ERK MAP kinase (MAPK; see <a href="/entry/176948">176948</a>) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. The phenotypically related cardiofaciocutaneous syndrome (CFCS; <a href="/entry/115150">115150</a>) is caused by gain-of-function mutations in 1 of 4 different genes: KRAS, BRAF (<a href="/entry/164757">164757</a>), MEK1 (<a href="/entry/176872">176872</a>), or MEK2 (<a href="/entry/601263">601263</a>). The common features of these disorders probably result from increased ERK activation (<a href="#4" class="mim-tip-reference" title="Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S. &lt;strong&gt;Germline gain-of-function mutations in SOS1 cause Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 70-74, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143285/&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;17143285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1926&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="17143285">Roberts et al., 2007</a>). Discovery of these disease genes have established Noonan syndrome and related traits as disorders of dysregulated RAS-MAPK signaling (<a href="#5" class="mim-tip-reference" title="Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others. &lt;strong&gt;Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.&lt;/strong&gt; Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17143282/&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;17143282&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng1939&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="17143282">Tartaglia et al., 2007</a>). Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. They represent a major cause of Noonan syndrome and the first example of activating mutations in a RAS guanine nucleotide exchange factor (GEF) associated with human disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17143282+17143285" 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="#8" class="mim-tip-reference" title="Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others. &lt;strong&gt;SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)&lt;/strong&gt; J. Med. Genet. 44: 651-656, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17586837/&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;17586837&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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/10.1136/jmg.2007.051276&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="17586837">Zenker et al. (2007)</a> investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1, and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with Noonan syndrome, thus confirming SOS1 as the second major gene for that disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17586837" 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 10 affected members of a 3-generation family segregating NS4, <a href="#6" class="mim-tip-reference" title="van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I. &lt;strong&gt;Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.&lt;/strong&gt; Am. J. Med. Genet. 173A: 2968-2972, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28884940/&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;28884940&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.38466&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="28884940">van Trier et al. (2017)</a> identified a heterozygous missense mutation (P1045R; <a href="/entry/182530#0007">182530.0007</a>) in the SOS1 gene. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by <a href="#7" class="mim-tip-reference" title="van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C. &lt;strong&gt;External ear anomalies and hearing impairment in Noonan syndrome.&lt;/strong&gt; Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25862627/&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;25862627&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ijporl.2015.03.021&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="25862627">van Trier et al. (2015)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28884940+25862627" 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="Ferrero2008" class="mim-anchor"></a>
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Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C.
<strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong>
Europ. J. Med. Genet. 51: 566-572, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18678287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18678287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18678287" 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/j.ejmg.2008.06.011" target="_blank">Full Text</a>]
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<a id="Hanna2009" class="mim-anchor"></a>
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Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H.
<strong>SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.</strong>
Clin. Genet. 75: 568-571, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19438935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19438935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19438935" 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.1399-0004.2009.01149.x" target="_blank">Full Text</a>]
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<a id="Mascheroni2008" class="mim-anchor"></a>
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Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G.
<strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong>
Am. J. Med. Genet. 146A: 2966-2967, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18925667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18925667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18925667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.32538" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Roberts2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S.
<strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong>
Nature Genet. 39: 70-74, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17143285" 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/ng1926" target="_blank">Full Text</a>]
</p>
</div>
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<li>
<a id="5" class="mim-anchor"></a>
<a id="Tartaglia2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others.
<strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong>
Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17143282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17143282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17143282" 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/ng1939" target="_blank">Full Text</a>]
</p>
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<a id="6" class="mim-anchor"></a>
<a id="van Trier2017" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I.
<strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong>
Am. J. Med. Genet. 173A: 2968-2972, 2017.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28884940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28884940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28884940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.38466" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="van Trier2015" class="mim-anchor"></a>
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<p class="mim-text-font">
van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C.
<strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong>
Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25862627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25862627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25862627" 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/j.ijporl.2015.03.021" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Zenker2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others.
<strong>SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)</strong>
J. Med. Genet. 44: 651-656, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17586837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17586837</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17586837[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=17586837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.2007.051276" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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Hilary J. Vernon - updated : 07/07/2020
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Cassandra L. Kniffin - updated : 10/26/2010<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Victor A. McKusick - updated : 1/25/2008
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Victor A. McKusick : 1/30/2007
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carol : 10/29/2021
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carol : 07/07/2020<br>carol : 12/01/2014<br>terry : 4/9/2012<br>wwang : 11/5/2010<br>ckniffin : 10/26/2010<br>wwang : 10/6/2010<br>alopez : 1/28/2010<br>wwang : 7/21/2009<br>ckniffin : 6/18/2009<br>wwang : 3/10/2009<br>ckniffin : 3/3/2009<br>alopez : 1/25/2008<br>alopez : 2/19/2007<br>alopez : 1/31/2007
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<h3>
<span class="mim-font">
<strong>#</strong> 610733
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NOONAN SYNDROME 4; NS4
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<strong>ORPHA:</strong> 648; &nbsp;
<strong>DO:</strong> 0060582; &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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2p22.1
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Noonan syndrome 4
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610733
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Autosomal dominant
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3
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SOS1
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182530
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Noonan syndrome-4 (NS4) is caused by heterozygous mutation in the SOS1 gene (182530) on chromosome 2p22.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).</p>
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<strong>Description</strong>
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<p>Noonan syndrome-4 (NS4) is an autosomal dominant disorder characterized by a variable phenotype comprising short stature, congenital heart defects, and facial dysmorphisms (summary by Ferrero et al., 2008). Patients often have ectodermal anomalies, such as keratitis pilaris, curly hair, and ocular ptosis (Tartaglia et al., 2007; Zenker et al., 2007). </p>
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<strong>Clinical Features</strong>
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<p>Roberts et al. (2007) and Tartaglia et al. (2007) delineated a Noonan syndrome phenotype caused by mutation in the SOS1 gene that lies within the Noonan syndrome spectrum but is distinctive. Roberts et al. (2007) noted 2 significant differences: pulmonic stenosis was more frequent in patients with SOS1 mutations than in those without SOS1 or PTPN11 mutations, and atrial septal defect was relatively rare in affected individuals with SOS1 mutations compared to those with PTPN11 mutations. Tartaglia et al. (2007) noted ectodermal features including keratosis pilaris and curly hair that were significantly more prevalent among individuals with an SOS1 mutation compared with the general Noonan population. They observed height below the third percentile in only 2 of 15 individuals with an SOS1 mutation, whereas the prevalence is approximately 70% among patients with Noonan syndrome in general and among those with a PTPN11 mutation. In contrast, macrocephaly was overrepresented among those with SOS1 mutations. Only one individual with an SOS1 mutation had mental retardation, potentially attributable to critical illness as a newborn. In comparison, 30% of all children with Noonan syndrome require special education. </p><p>Zenker et al. (2007) reported that Noonan syndrome patients with SOS1 mutations commonly had ectodermal manifestations including keratosis pilaris of the face, sparse eyebrows, curly hair, and, in 1 patient, ichthyosiform skin changes. By comparing clinical features of a cohort of 42 patients with PTPN11 mutations derived from a previous study with those of their current study of 28 patients with SOS1 mutations, Zenker et al. (2007) confirmed a significantly higher prevalence of keratosis pilaris/hyperkeratotic skin and curly hair in patients with SOS1 mutations compared with those with PTP11 alterations (58% vs 6% and 78% vs 34%, respectively). Moreover, ocular ptosis was observed more frequently in patients with NS with SOS1 mutations than in patients with a PTPN11 mutation (80% vs 54%). </p><p>Ferrero et al. (2008) reported a newborn with Noonan syndrome due to SOS1 mutation (T266K; 182530.0002). He presented with facial dysmorphisms and prenatal anomalies, not associated with other congenital defects. The pregnancy was characterized by polyhydramnios and increased fetal nuchal translucency. Dysmorphic facial features included hypertelorism, epicanthal folds, flat nasal bridge, low-set posteriorly rotated ears, and short neck. Other features included moderated pulmonic stenosis and bilateral cryptorchidism. Developmental milestones were normal at 24 months of age. There were no coagulation abnormalities. </p><p>Van Trier et al. (2017) reported 10 members of a 3-generation family with NS4. The patients, who ranged in age from 8 to 73 years, had variable phenotypic expression, ranging from almost no clinical characteristics to a typical presentation. Three family members had suggestive facial characteristics of NS4, whereas 2 had typical facial features. Four patients had pectus excavatum. Seven patients had ptosis and 6 had sparse eyebrows. One patient had intellectual delay and 5 had motor delays. Two had sensorineural hearing loss. None of the patients had short stature, lymphatic dysplasia, cryptorchidism, skin findings, or congenital heart disease. </p>
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<strong>Other Features</strong>
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<p>Mascheroni et al. (2008) reported a girl with NS4 who presented at age 13 years with swelling and severe pain in her right foot and ankle, which was found to result from pigmented villonodular synovitis (PVNS). Histologically, the synovia was hyperplastic, with villi covered by reactive-appearing synovial cells in multiple layers and histio-fibroblastic and capillary proliferation. History revealed that she had congenital pulmonary valve stenosis and ventricular septal defect, and a coagulopathy with partial factor VIII and XI deficiencies. Physical examination showed short stature, curly hair, sparse eyebrows, hypertelorism, flat nasal bridge, epicanthal folds, prominent pale blue eyes, bilateral ptosis, thick lips, low-set retroverted ears with thickened helices, facial keratosis pilaris, wide-spaced nipples, pectus excavatum, and scoliosis. Psychomotor and cognitive development was normal. Mascheroni et al. (2008) suggested that PVNS is a proliferative lesion that can be part of the phenotypic spectrum of Noonan syndrome. </p><p>Hanna et al. (2009) reported 2 brothers, born of consanguineous parents, with Noonan syndrome-like disorder with multiple giant cell lesions. One boy presented at age 4.5 years with a 2-year history of bilateral progressive swelling of the mandible. A preliminary diagnosis of cherubism (118400) was considered. Radiographic studies showed multilocular lesions of the mandibular rami, consistent with giant cell lesions. The boy's 6.5-year-old brother presented with severe pulmonary valvular stenosis and was found to have similar multilocular lesions of the mandible as his brother. Both boys had characteristic facial features of Noonan syndrome, including high anterior hairline with frontal bossing, follicular hyperkeratosis of the forehead (keratosis pilaris), depressed nasal bridge, hypertelorism, downslanting palpebral fissures, and low-set and posteriorly angulated ears with thick helices. Other features included short neck and widely spaced nipples. Both showed normal development and normal stature. The father showed milder features of the disorder, with long face, downslanting palpebral fissures, low-set ears, and widely spaced nipples. Molecular studies identified a heterozygous mutation in the SOS1 gene (W432R; 182530.0006) in all 3 individuals. </p>
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<strong>Molecular Genetics</strong>
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<p>Roberts et al. (2007) and Tartaglia et al. (2007) found mutation in the SOS1 gene (182530) in Noonan syndrome patients without mutation in PTPN11 (176876) or KRAS2 (190070). Gain-of-function mutations in PTPN11, which encodes the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases, and less than 5% of cases are caused by mutations in KRAS2. SHP2 is required for RAS-ERK MAP kinase (MAPK; see 176948) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. The phenotypically related cardiofaciocutaneous syndrome (CFCS; 115150) is caused by gain-of-function mutations in 1 of 4 different genes: KRAS, BRAF (164757), MEK1 (176872), or MEK2 (601263). The common features of these disorders probably result from increased ERK activation (Roberts et al., 2007). Discovery of these disease genes have established Noonan syndrome and related traits as disorders of dysregulated RAS-MAPK signaling (Tartaglia et al., 2007). Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. They represent a major cause of Noonan syndrome and the first example of activating mutations in a RAS guanine nucleotide exchange factor (GEF) associated with human disease. </p><p>Zenker et al. (2007) investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1, and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with Noonan syndrome, thus confirming SOS1 as the second major gene for that disorder. </p><p>In 10 affected members of a 3-generation family segregating NS4, van Trier et al. (2017) identified a heterozygous missense mutation (P1045R; 182530.0007) in the SOS1 gene. The mutation was identified in the proband (patient IV-8) by next-generation sequencing of an NS gene panel and in additional family members by Sanger sequencing. No other pathogenic mutations or variants of uncertain significance were identified. There was a range of clinical expression among the 10 family members from almost no NS4 characteristics to a typical presentation. The family was part of an NS cohort previously studied by van Trier et al. (2015). </p>
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<h4>
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<strong>REFERENCES</strong>
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Ferrero, G. B., Baldassarre, G., Delmonaco, A. G., Biamino, E., Banaudi, E., Carta, C., Rossi, C., Silengo, M. C.
<strong>Clinical and molecular characterization of 40 patients with Noonan syndrome.</strong>
Europ. J. Med. Genet. 51: 566-572, 2008.
[PubMed: 18678287]
[Full Text: https://doi.org/10.1016/j.ejmg.2008.06.011]
</p>
</li>
<li>
<p class="mim-text-font">
Hanna, N., Parfait, B., Talaat, I. M., Vidaud, M., Elsedfy, H. H.
<strong>SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.</strong>
Clin. Genet. 75: 568-571, 2009.
[PubMed: 19438935]
[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01149.x]
</p>
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<li>
<p class="mim-text-font">
Mascheroni, E., Digilio, M. C., Cortis, E., Devito, R., Sarkozy, A., Capolino, R., Dallapiccola, B., Ugazio, A. G.
<strong>Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. (Letter)</strong>
Am. J. Med. Genet. 146A: 2966-2967, 2008.
[PubMed: 18925667]
[Full Text: https://doi.org/10.1002/ajmg.a.32538]
</p>
</li>
<li>
<p class="mim-text-font">
Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., Kucherlapati, R. S.
<strong>Germline gain-of-function mutations in SOS1 cause Noonan syndrome.</strong>
Nature Genet. 39: 70-74, 2007.
[PubMed: 17143285]
[Full Text: https://doi.org/10.1038/ng1926]
</p>
</li>
<li>
<p class="mim-text-font">
Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., and 13 others.
<strong>Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome.</strong>
Nature Genet. 39: 75-79, 2007. Note: Erratum: Nature Genet. 39: 276 only, 2007.
[PubMed: 17143282]
[Full Text: https://doi.org/10.1038/ng1939]
</p>
</li>
<li>
<p class="mim-text-font">
van Trier, D. C., Rinne, T., Noordam, K., Draaisma, J. M., van der Burgt, I.
<strong>Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation.</strong>
Am. J. Med. Genet. 173A: 2968-2972, 2017.
[PubMed: 28884940]
[Full Text: https://doi.org/10.1002/ajmg.a.38466]
</p>
</li>
<li>
<p class="mim-text-font">
van Trier, D. C., van Nierop, J., Draaisma, J. M., van der Burgt, I., Kunst, H., Croonen, E. A., Admiraal, R. J. C.
<strong>External ear anomalies and hearing impairment in Noonan syndrome.</strong>
Int. J. Pediat. Otorhinolaryng. 79: 874-878, 2015.
[PubMed: 25862627]
[Full Text: https://doi.org/10.1016/j.ijporl.2015.03.021]
</p>
</li>
<li>
<p class="mim-text-font">
Zenker, M., Horn, D., Wieczorek, D., Allanson, J., Pauli, S., van der Burgt, I., Doerr, H.-G., Gaspar, H., Hofbeck, M., Gillessen-Kaesbach, G., Koch, A., Meinecke, P., and 13 others.
<strong>SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. (Letter)</strong>
J. Med. Genet. 44: 651-656, 2007.
[PubMed: 17586837]
[Full Text: https://doi.org/10.1136/jmg.2007.051276]
</p>
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 07/07/2020<br>Cassandra L. Kniffin - updated : 10/26/2010<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Victor A. McKusick - updated : 1/25/2008
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Creation Date:
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