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<title>
Entry
- #603387 - MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1
- OMIM
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<span class="h4">#603387</span>
<br />
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/603387"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS603387"> <strong>Phenotypic Series</strong> </a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS 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>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11582&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK396098/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83473" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/ff5bf120-5dbb-4c05-ba0e-721890182891/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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603387
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<h3>
<span class="mim-font">
MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MEGALENCEPHALY, POLYMICROGYRIA, MEGA CORPUS CALLOSUM SYNDROME; MPPH<br />
MEG-PMG-MEGACC SYNDROME<br />
MEGALENCEPHALY, MEGA CORPUS CALLOSUM, AND COMPLETE LACK OF MOTOR DEVELOPMENT
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/453?start=-3&limit=10&highlight=453">
19p13.11
</a>
</span>
</td>
<td>
<span class="mim-font">
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603387"> 603387 </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">
PIK3R2
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603157"> 603157 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/603387" 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/PS603387" 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/603387" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/603387" 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">
- Small birth length <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551528</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> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Large eyes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855852&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855852</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001090" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001090</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001090" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001090</a>]</span><br /> -
Blindness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span><br /> -
Pale optic nerves <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551529&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551529</a>]</span><br /> -
Wide palpebral fissures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849340&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849340</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000637" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000637</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000637" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000637</a>]</span><br /> -
Eyelid 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>]</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> 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><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">
- Low 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><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">
- Tent-shaped mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2750539&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2750539</a>]</span><br /> -
Prominent philtral groove <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551530</a>]</span><br /> -
Submucous cleft palate (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/763108005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">763108005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551487&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551487</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:5201016" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:5201016</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:5201016" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:5201016</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=b1095da353de35a140f68923e654feb4" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Palate,Submucous_Cleft-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=b1095da353de35a140f68923e654feb4&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">
- Atrial septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
Ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
Vascular ring <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110409004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110409004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/66403007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">66403007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.45" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.45</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221214</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010775" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010775</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010775" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010775</a>]</span><br /> -
Mitral regurgitation, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551535</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001653</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001653</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48724000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48724000</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> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Duplicated kidneys (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315787&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315787</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">
- Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br /> -
S-scoliosis of thoracic spine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551533&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551533</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">
- Flexion contractures at both knees <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/202289003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">202289003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0409355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0409355</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006380</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006380</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Postaxial polydactyly <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220697</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100259</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Muscle atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br />
</span>
</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">
- Diffuse hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1969871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1969871</a>]</span><br /> -
Axial hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Mental retardation, profound <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31216003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31216003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F73</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020796&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020796</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002187</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002187</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span><br /> -
No language <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551521&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551521</a>]</span><br /> -
Increased tendon reflex <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Megalencephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9740002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9740002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.5</a>, <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=C2720434&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2720434</a> HPO: <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:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span><br /> -
Thick corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007074" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007074</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007074" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007074</a>]</span><br /> -
Mildly thin corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551523&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551523</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033725</a>]</span><br /> -
Enlarged white matter <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551524</a>]</span><br /> -
Focal pachygyria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855723&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855723</a>]</span><br /> -
Polymicrogyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4945003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4945003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266464</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span><br /> -
Wide Sylvian fissures with incomplete opercularization <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551525</a>]</span><br /> -
Ventricles slightly enlarged <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3554751&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3554751</a>]</span><br /> -
Hydrocephalus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020255&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020255</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br /> -
Cavum septi pellucidi <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74968005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74968005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0228158&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0228158</a>]</span><br /> -
Cavum vergae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33191008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33191008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0228159&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0228159</a>]</span><br /> -
Small cavum septum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551526</a>]</span><br />
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<em> Behavioral Psychiatric Manifestations </em>
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- Asperger-like features <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551522&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551522</a>]</span><br />
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<strong> NEOPLASIA </strong>
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- Increased risk of medulloblastoma (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551532&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551532</a>]</span><br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the phosphatidylinositol 3-kinase, regulatory subunit 2 gene (PIK3R2, <a href="/entry/603157#0001">603157.0001</a>)<br />
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<h5>
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
- <a href="/phenotypicSeries/PS603387">PS603387</a>
- 3 Entries
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<strong>Location</strong>
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<strong>Phenotype</strong>
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<strong>Inheritance</strong>
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<strong>Phenotype<br />mapping key</strong>
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<strong>Phenotype<br />MIM number</strong>
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<strong>Gene/Locus</strong>
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<strong>Gene/Locus<br />MIM number</strong>
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<span class="mim-font">
<a href="/geneMap/1/1845?start=-3&limit=10&highlight=1845"> 1q43-q44 </a>
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<span class="mim-font">
<a href="/entry/615937"> Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/615937"> 615937 </a>
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<a href="/entry/611223"> AKT3 </a>
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<a href="/entry/611223"> 611223 </a>
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<a href="/geneMap/12/30?start=-3&limit=10&highlight=30"> 12p13.32 </a>
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<span class="mim-font">
<a href="/entry/615938"> Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 </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/615938"> 615938 </a>
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<a href="/entry/123833"> CCND2 </a>
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<span class="mim-font">
<a href="/entry/123833"> 123833 </a>
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<span class="mim-font">
<a href="/geneMap/19/453?start=-3&limit=10&highlight=453"> 19p13.11 </a>
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<td>
<span class="mim-font">
<a href="/entry/603387"> Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 </a>
</span>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
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<td>
<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/603387"> 603387 </a>
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<span class="mim-font">
<a href="/entry/603157"> PIK3R2 </a>
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<span class="mim-font">
<a href="/entry/603157"> 603157 </a>
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1 (MPPH1) is caused by heterozygous mutation in the PIK3R2 gene (<a href="/entry/603157">603157</a>) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>This disorder comprises megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome (MCAP; <a href="/entry/602501">602501</a>) (summary by <a href="#3" class="mim-tip-reference" title="Gripp, K. W., Hopkins, E., Vinkler, C., Lev, D., Malinger, G., Lerman-Sagie, T., Dobyns, W. B. &lt;strong&gt;Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes.&lt;/strong&gt; Am. J. Med. Genet. 149A: 868-876, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19353582/&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;19353582&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32732&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="19353582">Gripp et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19353582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of the Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome</em></strong></p><p>
See also MPPH2 (<a href="/entry/615937">615937</a>), caused by mutation in the AKT3 gene (<a href="/entry/611223">611223</a>) on chromosome 1q43-q44; and MPPH3 (<a href="/entry/615938">615938</a>), caused by mutation in the CCND2 gene (<a href="/entry/123833">123833</a>) on chromosome 12p13.</p>
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<strong>Clinical Features</strong>
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<p><a href="#2" class="mim-tip-reference" title="Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 161-167, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9788554/&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;9788554&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9788554">Gohlich-Ratmann et al. (1998)</a> reported 3 sporadic cases of in utero-onset megalencephaly. The children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5 to 6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nasal bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Formation of the frontoparietal operculum was incomplete, and the Sylvian fissures were wide. <a href="#2" class="mim-tip-reference" title="Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 161-167, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9788554/&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;9788554&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9788554">Gohlich-Ratmann et al. (1998)</a> knew of no reports of similar cases. On review of the MRI figures in the paper by <a href="#2" class="mim-tip-reference" title="Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 161-167, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9788554/&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;9788554&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9788554">Gohlich-Ratmann et al. (1998)</a>, <a href="#5" class="mim-tip-reference" title="Mirzaa, G., Dodge, N. N., Glass, I., Day, C., Gripp, K., Nicholson, L., Straub, V., Voit, T., Dobyns, W. B. &lt;strong&gt;Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.&lt;/strong&gt; Neuropediatrics 35: 353-359, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15627943/&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;15627943&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2004-830497&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="15627943">Mirzaa et al. (2004)</a> concluded that the cortical dysplasia suggested polymicrogyria rather than typical pachygyria, a point with which the authors of the 1998 paper agreed. <a href="#5" class="mim-tip-reference" title="Mirzaa, G., Dodge, N. N., Glass, I., Day, C., Gripp, K., Nicholson, L., Straub, V., Voit, T., Dobyns, W. B. &lt;strong&gt;Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.&lt;/strong&gt; Neuropediatrics 35: 353-359, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15627943/&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;15627943&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2004-830497&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="15627943">Mirzaa et al. (2004)</a> thus suggested the designation megalencephaly-polymicrogyria-mega-corpus callosum (MEG-PMG-MegaCC) syndrome. Postaxial polydactyly was also seen in the patients reported by <a href="#5" class="mim-tip-reference" title="Mirzaa, G., Dodge, N. N., Glass, I., Day, C., Gripp, K., Nicholson, L., Straub, V., Voit, T., Dobyns, W. B. &lt;strong&gt;Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.&lt;/strong&gt; Neuropediatrics 35: 353-359, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15627943/&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;15627943&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2004-830497&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="15627943">Mirzaa et al. (2004)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15627943+9788554" 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="#9" class="mim-tip-reference" title="Tohyama, J., Akasaka, N., Saito, N., Yoshimura, J., Nishiyama, K., Kato, M. &lt;strong&gt;Megalencephaly and polymicrogyria with polydactyly syndrome.&lt;/strong&gt; Pediat. Neurol. 37: 148-151, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17675034/&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;17675034&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.pediatrneurol.2007.04.008&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="17675034">Tohyama et al. (2007)</a> reported a Japanese girl with MPPH. She was noted to have enlarged ventricles on prenatal ultrasound at 30 weeks' gestational age. At birth, she had macrocephaly (+3.5 SD) and polydactyly of the lower limbs. She developed partially refractory seizures at age 3 months, and showed global developmental delay. Dysmorphic features included prominent forehead, hypertelorism, telecanthus, and depressed nasal bridge. Se also had visual impairment, but ophthalmic examination was normal. Brain MRI showed polymicrogyria, decreased white matter volume, and signal abnormalities in the occipital lobe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17675034" 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="Dagli, A. I., Stalker, H. J., Williams, C. A. &lt;strong&gt;A patient with the syndrome of megalencephaly, mega corpus callosum and complete lack of motor development.&lt;/strong&gt; Am. J. Med. Genet. 146A: 204-207, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18076119/&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;18076119&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32079&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="18076119">Dagli et al. (2008)</a> reported a female infant with a phenotype similar to that described by <a href="#2" class="mim-tip-reference" title="Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.&lt;/strong&gt; Am. J. Med. Genet. 79: 161-167, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9788554/&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;9788554&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9788554">Gohlich-Ratmann et al. (1998)</a>. At birth, she had macrocephaly, hypotonia, frontal bossing, depressed nasal bridge, and normal brain MRI. Features noted later included open anterior fontanel, wide palpebral fissures, ptosis, and profound mental retardation with no psychomotor development. Brain MRI at age 15 months showed bilateral megalencephaly with generalized thickening of the cortex, severe enlargement of the corpus callosum, and a cavum septum pellucidum. There was abnormal sulcation, which may be seen with polymicrogyria. The ventricles were normal in size, and the Sylvian fissures were not wide. The patient died at home at 21 months of age from respiratory complications associated with a flu-like illness. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9788554+18076119" 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="#4" class="mim-tip-reference" title="Hengst, M., Tucke, J., Zerres, K., Blaum, M., Hausler, M. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: delineation of a rare syndrome.&lt;/strong&gt; Am. J. Med. Genet. 152A: 2360-2364, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20803648/&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;20803648&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33577&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="20803648">Hengst et al. (2010)</a> reported a 3-year-old girl who was born with macrocephaly and showed hypotonia, reduced spontaneous movements, and severely delayed motor development. Brain MRI at age 8 months showed extensive polymicrogyria sparing the midline cortical structures and the visual cortex, a markedly enlarged corpus callosum, and megalencephaly of the hemispheres and cerebellum. There was increased diameter of the internal cerebral vein, the vein of Galen, and the straight sinus. By age 2 years, she had learned to control her head for a short time and to roll around, but could not sit or grasp. She had hypotonia, with salivation, mental retardation, and lack of speech. There was no facial dysmorphism and she did not have seizures. <a href="#4" class="mim-tip-reference" title="Hengst, M., Tucke, J., Zerres, K., Blaum, M., Hausler, M. &lt;strong&gt;Megalencephaly, mega corpus callosum, and complete lack of motor development: delineation of a rare syndrome.&lt;/strong&gt; Am. J. Med. Genet. 152A: 2360-2364, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20803648/&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;20803648&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33577&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="20803648">Hengst et al. (2010)</a> suggested the term 'megalencephaly-mega corpus callosum-motor retardation syndrome (MMM)' as a more accurate designation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20803648" 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>The transmission pattern of MPPH1 in the family reported by <a href="#8" class="mim-tip-reference" title="Riviere, J.-B., Mirzaa, G. M., O&#x27;Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., and 29 others. &lt;strong&gt;De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.&lt;/strong&gt; Nature Genet. 44: 934-940, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22729224/&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;22729224&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22729224[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/10.1038/ng.2331&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="22729224">Riviere et al. (2012)</a> was consistent with autosomal dominant inheritance from a parent with somatic and germline mosaicism. The heterozygous mutations in the PIK3R2 gene that were identified in other patients with MPPH1 by <a href="#8" class="mim-tip-reference" title="Riviere, J.-B., Mirzaa, G. M., O&#x27;Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., and 29 others. &lt;strong&gt;De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.&lt;/strong&gt; Nature Genet. 44: 934-940, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22729224/&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;22729224&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22729224[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/10.1038/ng.2331&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="22729224">Riviere et al. (2012)</a>, and in a Japanese girl reported by <a href="#9" class="mim-tip-reference" title="Tohyama, J., Akasaka, N., Saito, N., Yoshimura, J., Nishiyama, K., Kato, M. &lt;strong&gt;Megalencephaly and polymicrogyria with polydactyly syndrome.&lt;/strong&gt; Pediat. Neurol. 37: 148-151, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17675034/&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;17675034&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.pediatrneurol.2007.04.008&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="17675034">Tohyama et al. (2007)</a> and <a href="#7" class="mim-tip-reference" title="Nakamura, K., Kato, M., Tohyama, J., Shiohama, T., Hayasaka, K., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Matsumoto, N., Saitsu, H. &lt;strong&gt;AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. (Letter)&lt;/strong&gt; Clin. Genet. 85: 396-298, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23745724/&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;23745724&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/cge.12188&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="23745724">Nakamura et al. (2014)</a>, occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23745724+22729224+17675034" 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="#6" class="mim-tip-reference" title="Mirzaa, G. M., Conway, R. L., Gripp, K. W., Lerman-Sagie, T., Siegel, D. H., deVries, L. S., Lev, D., Kramer, N., Hopkins, E., Graham, J. M., Jr., Dobyns, W. B. &lt;strong&gt;Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.&lt;/strong&gt; Am. J. Med. Genet. 158A: 269-291, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22228622/&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;22228622&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34402&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="22228622">Mirzaa et al. (2012)</a> reviewed the phenotypic features of 42 patients with a megalencephalic syndrome in an attempt to clarify and simplify the categorization and diagnosis of these disorders. Statistical analysis of particular features yielded 2 main groups: 21 patients with a vascular malformation consistent with MCAP and 19 with no vascular malformation consistent with MPPH; 2 patients were in an overlap group. Vascular malformations were significantly associated with syndactyly and somatic overgrowth at birth, and lack of vascular malformations was associated with polydactyly. The various features were assigned to 5 major classes of developmental abnormalities. Both MCAP and MPPH had (1) megalencephaly and variable somatic overgrowth (particularly in MCAP); (2) distal limb malformations, syndactyly being more associated with MCAP and polydactyly with MPPH; and (3) similar cortical brain malformations (mainly polymicrogyria). In addition, MCAP included (4) developmental vascular abnormalities and (5) occasional connective tissue dysplasia, such as hyperelasticity or thick skin. MPPH lacks vascular malformations, connective tissue dysplasia, and heterotopia. Based on these findings, <a href="#6" class="mim-tip-reference" title="Mirzaa, G. M., Conway, R. L., Gripp, K. W., Lerman-Sagie, T., Siegel, D. H., deVries, L. S., Lev, D., Kramer, N., Hopkins, E., Graham, J. M., Jr., Dobyns, W. B. &lt;strong&gt;Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.&lt;/strong&gt; Am. J. Med. Genet. 158A: 269-291, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22228622/&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;22228622&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34402&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="22228622">Mirzaa et al. (2012)</a> proposed diagnostic criteria for the MCAP and MPPH syndromes, and postulated that the 2 disorders represent different, although overlapping, syndromes that may be caused by different genes involved in the same biologic pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22228622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Molecular Genetics</strong>
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<p><a href="#8" class="mim-tip-reference" title="Riviere, J.-B., Mirzaa, G. M., O&#x27;Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., and 29 others. &lt;strong&gt;De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.&lt;/strong&gt; Nature Genet. 44: 934-940, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22729224/&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;22729224&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22729224[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/10.1038/ng.2331&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="22729224">Riviere et al. (2012)</a> performed exome sequencing in the oldest of 3 affected sibs with MPPH and identified a heterozygous mutation in the PIK3R2 gene (G373R; <a href="/entry/603157#0001">603157.0001</a>), which encodes the p85B regulatory subunit of class IA PI3K. Sanger sequencing confirmed the presence of the mutation in all 3 affected sibs and its absence in the saliva and blood of both parents and the unaffected sister, showing germline mosaicism in 1 parent. Sequencing of the PIK3R2 gene in 40 individuals with megalencephaly identified the same nucleotide change in 10 additional subjects with MPPH, and this mutation was shown to be de novo in all subjects for whom parental DNA was available. The mutation occurred at a CpG dinucleotide, which might explain its recurrence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22729224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Japanese girl with MPPH originally reported by <a href="#9" class="mim-tip-reference" title="Tohyama, J., Akasaka, N., Saito, N., Yoshimura, J., Nishiyama, K., Kato, M. &lt;strong&gt;Megalencephaly and polymicrogyria with polydactyly syndrome.&lt;/strong&gt; Pediat. Neurol. 37: 148-151, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17675034/&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;17675034&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.pediatrneurol.2007.04.008&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="17675034">Tohyama et al. (2007)</a>, <a href="#7" class="mim-tip-reference" title="Nakamura, K., Kato, M., Tohyama, J., Shiohama, T., Hayasaka, K., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Matsumoto, N., Saitsu, H. &lt;strong&gt;AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. (Letter)&lt;/strong&gt; Clin. Genet. 85: 396-298, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23745724/&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;23745724&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/cge.12188&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="23745724">Nakamura et al. (2014)</a> identified a de novo heterozygous missense mutation in the PIK3R2 gene (L401P; <a href="/entry/603157#0002">603157.0002</a>). Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23745724+17675034" 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>REFERENCES</strong>
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<a id="Dagli2008" class="mim-anchor"></a>
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Dagli, A. I., Stalker, H. J., Williams, C. A.
<strong>A patient with the syndrome of megalencephaly, mega corpus callosum and complete lack of motor development.</strong>
Am. J. Med. Genet. 146A: 204-207, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18076119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18076119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18076119" 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.32079" target="_blank">Full Text</a>]
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<a id="Gohlich-Ratmann1998" class="mim-anchor"></a>
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Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T.
<strong>Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.</strong>
Am. J. Med. Genet. 79: 161-167, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9788554/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9788554</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9788554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q" target="_blank">Full Text</a>]
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<a id="Gripp2009" class="mim-anchor"></a>
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Gripp, K. W., Hopkins, E., Vinkler, C., Lev, D., Malinger, G., Lerman-Sagie, T., Dobyns, W. B.
<strong>Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes.</strong>
Am. J. Med. Genet. 149A: 868-876, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19353582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19353582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19353582" 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.32732" target="_blank">Full Text</a>]
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<a id="Hengst2010" class="mim-anchor"></a>
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Hengst, M., Tucke, J., Zerres, K., Blaum, M., Hausler, M.
<strong>Megalencephaly, mega corpus callosum, and complete lack of motor development: delineation of a rare syndrome.</strong>
Am. J. Med. Genet. 152A: 2360-2364, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20803648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20803648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20803648" 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.33577" target="_blank">Full Text</a>]
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<a id="Mirzaa2004" class="mim-anchor"></a>
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<p class="mim-text-font">
Mirzaa, G., Dodge, N. N., Glass, I., Day, C., Gripp, K., Nicholson, L., Straub, V., Voit, T., Dobyns, W. B.
<strong>Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.</strong>
Neuropediatrics 35: 353-359, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15627943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15627943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15627943" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1055/s-2004-830497" target="_blank">Full Text</a>]
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<a id="Mirzaa2012" class="mim-anchor"></a>
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<p class="mim-text-font">
Mirzaa, G. M., Conway, R. L., Gripp, K. W., Lerman-Sagie, T., Siegel, D. H., deVries, L. S., Lev, D., Kramer, N., Hopkins, E., Graham, J. M., Jr., Dobyns, W. B.
<strong>Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.</strong>
Am. J. Med. Genet. 158A: 269-291, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22228622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22228622</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22228622" 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.34402" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="Nakamura2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nakamura, K., Kato, M., Tohyama, J., Shiohama, T., Hayasaka, K., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Matsumoto, N., Saitsu, H.
<strong>AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. (Letter)</strong>
Clin. Genet. 85: 396-298, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23745724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23745724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23745724" 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/cge.12188" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
<a id="Riviere2012" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Riviere, J.-B., Mirzaa, G. M., O'Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., and 29 others.
<strong>De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.</strong>
Nature Genet. 44: 934-940, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22729224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22729224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22729224[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=22729224" 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/ng.2331" target="_blank">Full Text</a>]
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<a id="Tohyama2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tohyama, J., Akasaka, N., Saito, N., Yoshimura, J., Nishiyama, K., Kato, M.
<strong>Megalencephaly and polymicrogyria with polydactyly syndrome.</strong>
Pediat. Neurol. 37: 148-151, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17675034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17675034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17675034" 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.pediatrneurol.2007.04.008" target="_blank">Full Text</a>]
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<span class="mim-text-font">
Cassandra L. Kniffin - updated : 8/12/2014
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Nara Sobreira - updated : 11/21/2012<br>Nara Sobreira - updated : 11/20/2012<br>Cassandra L. Kniffin - updated : 4/10/2012<br>Cassandra L. Kniffin - updated : 6/15/2011<br>Cassandra L. Kniffin - updated : 10/19/2009<br>Cassandra L. Kniffin - updated : 7/21/2008
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Victor A. McKusick : 12/29/1998
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alopez : 09/18/2023
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alopez : 09/26/2018<br>carol : 08/20/2014<br>alopez : 8/19/2014<br>ckniffin : 8/12/2014<br>ckniffin : 6/12/2014<br>carol : 11/21/2012<br>carol : 11/20/2012<br>alopez : 4/12/2012<br>ckniffin : 4/10/2012<br>carol : 6/20/2011<br>ckniffin : 6/15/2011<br>wwang : 11/6/2009<br>ckniffin : 10/19/2009<br>wwang : 8/4/2008<br>ckniffin : 7/21/2008<br>carol : 12/29/1998
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<strong>#</strong> 603387
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MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1; MPPH1
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<em>Alternative titles; symbols</em>
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MEGALENCEPHALY, POLYMICROGYRIA, MEGA CORPUS CALLOSUM SYNDROME; MPPH<br />
MEG-PMG-MEGACC SYNDROME<br />
MEGALENCEPHALY, MEGA CORPUS CALLOSUM, AND COMPLETE LACK OF MOTOR DEVELOPMENT
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<strong>ORPHA:</strong> 83473; &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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19p13.11
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Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
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603387
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Autosomal dominant
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3
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PIK3R2
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603157
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1 (MPPH1) is caused by heterozygous mutation in the PIK3R2 gene (603157) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>This disorder comprises megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome (MCAP; 602501) (summary by Gripp et al., 2009). </p><p><strong><em>Genetic Heterogeneity of the Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome</em></strong></p><p>
See also MPPH2 (615937), caused by mutation in the AKT3 gene (611223) on chromosome 1q43-q44; and MPPH3 (615938), caused by mutation in the CCND2 gene (123833) on chromosome 12p13.</p>
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<strong>Clinical Features</strong>
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<p>Gohlich-Ratmann et al. (1998) reported 3 sporadic cases of in utero-onset megalencephaly. The children were born to healthy nonconsanguineous parents after uneventful pregnancies. Head circumferences were just above the 97th centile at birth in 2 patients, 2 cm above the 97th centile in 1 patient, and subsequently increased to 4.5 to 6.5 cm above the 97th centile at age 5 years. All patients completely lacked motor and speech development and showed very little intellectual progress. There was a distinctive facial aspect with frontal bossing, low nasal bridge, and large eyes, but no cutaneous abnormalities and no signs of other organ involvement. Magnetic resonance imaging showed bilateral megalencephaly with a broad corpus callosum, enlarged white matter, and focally thick gray matter, resulting in pachygyric appearance of the cortex. Formation of the frontoparietal operculum was incomplete, and the Sylvian fissures were wide. Gohlich-Ratmann et al. (1998) knew of no reports of similar cases. On review of the MRI figures in the paper by Gohlich-Ratmann et al. (1998), Mirzaa et al. (2004) concluded that the cortical dysplasia suggested polymicrogyria rather than typical pachygyria, a point with which the authors of the 1998 paper agreed. Mirzaa et al. (2004) thus suggested the designation megalencephaly-polymicrogyria-mega-corpus callosum (MEG-PMG-MegaCC) syndrome. Postaxial polydactyly was also seen in the patients reported by Mirzaa et al. (2004). </p><p>Tohyama et al. (2007) reported a Japanese girl with MPPH. She was noted to have enlarged ventricles on prenatal ultrasound at 30 weeks' gestational age. At birth, she had macrocephaly (+3.5 SD) and polydactyly of the lower limbs. She developed partially refractory seizures at age 3 months, and showed global developmental delay. Dysmorphic features included prominent forehead, hypertelorism, telecanthus, and depressed nasal bridge. Se also had visual impairment, but ophthalmic examination was normal. Brain MRI showed polymicrogyria, decreased white matter volume, and signal abnormalities in the occipital lobe. </p><p>Dagli et al. (2008) reported a female infant with a phenotype similar to that described by Gohlich-Ratmann et al. (1998). At birth, she had macrocephaly, hypotonia, frontal bossing, depressed nasal bridge, and normal brain MRI. Features noted later included open anterior fontanel, wide palpebral fissures, ptosis, and profound mental retardation with no psychomotor development. Brain MRI at age 15 months showed bilateral megalencephaly with generalized thickening of the cortex, severe enlargement of the corpus callosum, and a cavum septum pellucidum. There was abnormal sulcation, which may be seen with polymicrogyria. The ventricles were normal in size, and the Sylvian fissures were not wide. The patient died at home at 21 months of age from respiratory complications associated with a flu-like illness. </p><p>Hengst et al. (2010) reported a 3-year-old girl who was born with macrocephaly and showed hypotonia, reduced spontaneous movements, and severely delayed motor development. Brain MRI at age 8 months showed extensive polymicrogyria sparing the midline cortical structures and the visual cortex, a markedly enlarged corpus callosum, and megalencephaly of the hemispheres and cerebellum. There was increased diameter of the internal cerebral vein, the vein of Galen, and the straight sinus. By age 2 years, she had learned to control her head for a short time and to roll around, but could not sit or grasp. She had hypotonia, with salivation, mental retardation, and lack of speech. There was no facial dysmorphism and she did not have seizures. Hengst et al. (2010) suggested the term 'megalencephaly-mega corpus callosum-motor retardation syndrome (MMM)' as a more accurate designation. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of MPPH1 in the family reported by Riviere et al. (2012) was consistent with autosomal dominant inheritance from a parent with somatic and germline mosaicism. The heterozygous mutations in the PIK3R2 gene that were identified in other patients with MPPH1 by Riviere et al. (2012), and in a Japanese girl reported by Tohyama et al. (2007) and Nakamura et al. (2014), occurred de novo. </p>
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<strong>Diagnosis</strong>
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<p>Mirzaa et al. (2012) reviewed the phenotypic features of 42 patients with a megalencephalic syndrome in an attempt to clarify and simplify the categorization and diagnosis of these disorders. Statistical analysis of particular features yielded 2 main groups: 21 patients with a vascular malformation consistent with MCAP and 19 with no vascular malformation consistent with MPPH; 2 patients were in an overlap group. Vascular malformations were significantly associated with syndactyly and somatic overgrowth at birth, and lack of vascular malformations was associated with polydactyly. The various features were assigned to 5 major classes of developmental abnormalities. Both MCAP and MPPH had (1) megalencephaly and variable somatic overgrowth (particularly in MCAP); (2) distal limb malformations, syndactyly being more associated with MCAP and polydactyly with MPPH; and (3) similar cortical brain malformations (mainly polymicrogyria). In addition, MCAP included (4) developmental vascular abnormalities and (5) occasional connective tissue dysplasia, such as hyperelasticity or thick skin. MPPH lacks vascular malformations, connective tissue dysplasia, and heterotopia. Based on these findings, Mirzaa et al. (2012) proposed diagnostic criteria for the MCAP and MPPH syndromes, and postulated that the 2 disorders represent different, although overlapping, syndromes that may be caused by different genes involved in the same biologic pathway. </p>
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<strong>Molecular Genetics</strong>
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<p>Riviere et al. (2012) performed exome sequencing in the oldest of 3 affected sibs with MPPH and identified a heterozygous mutation in the PIK3R2 gene (G373R; 603157.0001), which encodes the p85B regulatory subunit of class IA PI3K. Sanger sequencing confirmed the presence of the mutation in all 3 affected sibs and its absence in the saliva and blood of both parents and the unaffected sister, showing germline mosaicism in 1 parent. Sequencing of the PIK3R2 gene in 40 individuals with megalencephaly identified the same nucleotide change in 10 additional subjects with MPPH, and this mutation was shown to be de novo in all subjects for whom parental DNA was available. The mutation occurred at a CpG dinucleotide, which might explain its recurrence. </p><p>In a Japanese girl with MPPH originally reported by Tohyama et al. (2007), Nakamura et al. (2014) identified a de novo heterozygous missense mutation in the PIK3R2 gene (L401P; 603157.0002). Functional studies of the variant were not performed. </p>
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<strong>REFERENCES</strong>
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Dagli, A. I., Stalker, H. J., Williams, C. A.
<strong>A patient with the syndrome of megalencephaly, mega corpus callosum and complete lack of motor development.</strong>
Am. J. Med. Genet. 146A: 204-207, 2008.
[PubMed: 18076119]
[Full Text: https://doi.org/10.1002/ajmg.a.32079]
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Gohlich-Ratmann, G., Baethmann, M., Lorenz, P., Gartner, J., Goebel, H. H., Engelbrecht, V., Christen, H.-J., Lenard, H.-G., Voit, T.
<strong>Megalencephaly, mega corpus callosum, and complete lack of motor development: a previously undescribed syndrome.</strong>
Am. J. Med. Genet. 79: 161-167, 1998.
[PubMed: 9788554]
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980923)79:3&lt;161::aid-ajmg2&gt;3.0.co;2-q]
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Gripp, K. W., Hopkins, E., Vinkler, C., Lev, D., Malinger, G., Lerman-Sagie, T., Dobyns, W. B.
<strong>Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes.</strong>
Am. J. Med. Genet. 149A: 868-876, 2009.
[PubMed: 19353582]
[Full Text: https://doi.org/10.1002/ajmg.a.32732]
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Hengst, M., Tucke, J., Zerres, K., Blaum, M., Hausler, M.
<strong>Megalencephaly, mega corpus callosum, and complete lack of motor development: delineation of a rare syndrome.</strong>
Am. J. Med. Genet. 152A: 2360-2364, 2010.
[PubMed: 20803648]
[Full Text: https://doi.org/10.1002/ajmg.a.33577]
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Mirzaa, G., Dodge, N. N., Glass, I., Day, C., Gripp, K., Nicholson, L., Straub, V., Voit, T., Dobyns, W. B.
<strong>Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.</strong>
Neuropediatrics 35: 353-359, 2004.
[PubMed: 15627943]
[Full Text: https://doi.org/10.1055/s-2004-830497]
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Mirzaa, G. M., Conway, R. L., Gripp, K. W., Lerman-Sagie, T., Siegel, D. H., deVries, L. S., Lev, D., Kramer, N., Hopkins, E., Graham, J. M., Jr., Dobyns, W. B.
<strong>Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.</strong>
Am. J. Med. Genet. 158A: 269-291, 2012.
[PubMed: 22228622]
[Full Text: https://doi.org/10.1002/ajmg.a.34402]
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Nakamura, K., Kato, M., Tohyama, J., Shiohama, T., Hayasaka, K., Nishiyama, K., Kodera, H., Nakashima, M., Tsurusaki, Y., Miyake, N., Matsumoto, N., Saitsu, H.
<strong>AKT3 and PIK3R2 mutations in two patients with megalencephaly-related syndromes: MCAP and MPPH. (Letter)</strong>
Clin. Genet. 85: 396-298, 2014.
[PubMed: 23745724]
[Full Text: https://doi.org/10.1111/cge.12188]
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Riviere, J.-B., Mirzaa, G. M., O'Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., and 29 others.
<strong>De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.</strong>
Nature Genet. 44: 934-940, 2012.
[PubMed: 22729224]
[Full Text: https://doi.org/10.1038/ng.2331]
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Tohyama, J., Akasaka, N., Saito, N., Yoshimura, J., Nishiyama, K., Kato, M.
<strong>Megalencephaly and polymicrogyria with polydactyly syndrome.</strong>
Pediat. Neurol. 37: 148-151, 2007.
[PubMed: 17675034]
[Full Text: https://doi.org/10.1016/j.pediatrneurol.2007.04.008]
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Cassandra L. Kniffin - updated : 8/12/2014<br>Nara Sobreira - updated : 11/21/2012<br>Nara Sobreira - updated : 11/20/2012<br>Cassandra L. Kniffin - updated : 4/10/2012<br>Cassandra L. Kniffin - updated : 6/15/2011<br>Cassandra L. Kniffin - updated : 10/19/2009<br>Cassandra L. Kniffin - updated : 7/21/2008
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Creation Date:
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Victor A. McKusick : 12/29/1998
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