2668 lines
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Entry
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- #605309 - MACROCEPHALY/AUTISM SYNDROME
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- OMIM
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<p>
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<span class="h4">#605309</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/605309"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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</div>
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<div id="mimFloatingLinksMenu">
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=(MACROCEPHALY/AUTISM SYNDROME) OR (PTEN)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18693&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>
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<div><a href="https://www.diseaseinfosearch.org/x/8775" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605309[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=210548" 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>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/7e340fa0-4cba-4eed-8926-1c9c1b4468e9/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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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0060867" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/605309" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0060867" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 210548<br />
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<strong>DO:</strong> 0060867<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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605309
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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MACROCEPHALY/AUTISM SYNDROME
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/10/368?start=-3&limit=10&highlight=368">
|
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10q23.31
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Macrocephaly/autism syndrome
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/605309"> 605309 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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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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</span>
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</td>
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<td>
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<span class="mim-font">
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PTEN
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/601728"> 601728 </a>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
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<a href="/clinicalSynopsis/605309" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
|
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/605309" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/605309" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> GROWTH </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Weight </em>
|
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</span>
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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|
|
- Obesity (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414915002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414915002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414916001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414916001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E66.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E66.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/278.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">278.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028754</a>, <a href="https://bioportal.bioontology.org/search?q=C4759928&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4759928</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001513" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001513</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001513" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001513</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
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</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Macrocephaly, postnatal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854417</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005490</a>]</span> <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> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Biparietal narrowing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004422" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004422</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004422" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004422</a>]</span><br />
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|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Broad forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Forehead,Broad-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Square outline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854419&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854419</a>]</span><br /> -
|
|
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="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
'Dished out' midface <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854420&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854420</a>]</span><br /> -
|
|
Long philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865014&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865014</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Philtrum,Long-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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</span>
|
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</div>
|
|
</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Short nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003196" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003196</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nose,Short-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=25661c4279536e7705f328dbb0964878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Depressed nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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</span>
|
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</div>
|
|
</div>
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</div>
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</div>
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
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|
|
</span>
|
|
</div>
|
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spleen </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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- Splenomegaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- 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 /> -
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Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</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> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Behavioral Psychiatric Manifestations </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Autism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35919005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35919005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/408857007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">408857007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43614003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43614003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/299" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/299.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/299.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0524528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0524528</a>, <a href="https://bioportal.bioontology.org/search?q=C0004352&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004352</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000717" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000717</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000717" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000717</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> IMMUNOLOGY </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
|
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|
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- Primary immunodeficiency (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/58606001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">58606001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0398686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0398686</a>]</span><br /> -
|
|
Recurrent infections (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/451991000124106" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">451991000124106</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239998</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span><br /> -
|
|
Opportunistic infections (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61274003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61274003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029118&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029118</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031690" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031690</a>]</span><br /> -
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Hypogammaglobulinemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119250001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119250001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D80.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D80.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/279.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">279.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086438</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span><br /> -
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Lymphopenia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48813009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48813009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853986&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853986</a>, <a href="https://bioportal.bioontology.org/search?q=C0024312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001888" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001888</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001888" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001888</a>]</span><br /> -
|
|
Inverted CD4/CD8 T cell ratio (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538498&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538498</a>]</span><br /> -
|
|
Decreased memory B cells (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3809931&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3809931</a>]</span><br /> -
|
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Decreased class-switched B cells (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4538499&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4538499</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the phosphatase and tensin homolog gene (PTEN, <a href="/entry/601728#0007">601728.0007</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that macrocephaly/autism syndrome is caused by heterozygous mutation in the PTEN gene (<a href="/entry/601728">601728</a>) on chromosome 10q23.</p><p>Heterozygous mutation in the PTEN gene can also cause Cowden syndrome (CWS1; <a href="/entry/158350">158350</a>), which shows some overlapping features.</p>
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</span>
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<div>
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<br />
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (<a href="#6" class="mim-tip-reference" title="Herman, G. E., Butter, E., Enrile, B., Pastore, M., Prior, T. W., Sommer, A. <strong>Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly.</strong> Am. J. Med. Genet. 143A: 589-593, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17286265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17286265</a>] [<a href="https://doi.org/10.1002/ajmg.a.31619" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17286265">Herman et al., 2007</a>). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (<a href="#12" class="mim-tip-reference" title="Tsujita, Y., Mitsui-Sekinaka, K., Imai, K., Yeh, T.-W., Mitsuiki, N., Asano, T., Ohnishi, H., Kato, Z., Sekinaka, Y., Zaha, K., Kato, T., Okano, T., and 21 others. <strong>Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase delta syndrome-like immunodeficiency.</strong> J. Allergy Clin. Immun. 138: 1672-1680, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27426521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27426521</a>] [<a href="https://doi.org/10.1016/j.jaci.2016.03.055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27426521">Tsujita et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27426521+17286265" 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>In the course of a clinical study of Sotos syndrome (<a href="/entry/117550">117550</a>), <a href="#5" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. <strong>Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?</strong> Am. J. Med. Genet. 41: 115-124, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1719811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1719811</a>] [<a href="https://doi.org/10.1002/ajmg.1320410128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1719811">Cole and Hughes (1991)</a> found that 6 of 79 probands who failed to fit that phenotype showed remarkable similarities to each other and to some of their first- and second-degree relatives. In addition to macrocephaly, affected individuals had typical facies characterized by square outline with frontal bossing, 'dished-out' midface, biparietal narrowing, and long philtrum. Birth weight and length were normal or near normal with subsequent obesity. <a href="#5" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. <strong>Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?</strong> Am. J. Med. Genet. 41: 115-124, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1719811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1719811</a>] [<a href="https://doi.org/10.1002/ajmg.1320410128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1719811">Cole and Hughes (1991)</a> were uncertain whether this represented a new entity or benign familial macrocephaly (<a href="/entry/153470">153470</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1719811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Naqvi, S., Cole, T., Graham, J. M., Jr. <strong>Cole-Hughes macrocephaly syndrome and associated autistic manifestations.</strong> Am. J. Med. Genet. 94: 149-152, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982971</a>] [<a href="https://doi.org/10.1002/1096-8628(20000911)94:2<149::aid-ajmg7>3.0.co;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982971">Naqvi et al. (2000)</a> reported 2 patients who had the same clinical features as the patients described by <a href="#5" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. <strong>Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?</strong> Am. J. Med. Genet. 41: 115-124, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1719811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1719811</a>] [<a href="https://doi.org/10.1002/ajmg.1320410128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1719811">Cole and Hughes (1991)</a> in addition to autistic characteristics with attention deficit disorder. The authors noted that the patients described by <a href="#5" class="mim-tip-reference" title="Cole, T. R. P., Hughes, H. E. <strong>Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?</strong> Am. J. Med. Genet. 41: 115-124, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1719811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1719811</a>] [<a href="https://doi.org/10.1002/ajmg.1320410128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1719811">Cole and Hughes (1991)</a> with adequate psychometric data had delays in language and social development much more prominent than delays in motor function, suggesting that some of these patients may have had autistic features. They also noted that <a href="#11" class="mim-tip-reference" title="Stevenson, R. E., Schroer, R. J., Skinner, C., Fender, D., Simensen, R. J. <strong>Autism and macrocephaly.</strong> Lancet 349: 1744-1745, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9193390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9193390</a>] [<a href="https://doi.org/10.1016/S0140-6736(05)62956-X" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9193390">Stevenson et al. (1997)</a> had found progressive postnatal macrocephaly in 24% of 100 patients with autism and that 62% of such cases had a family history of macrocephaly. <a href="#8" class="mim-tip-reference" title="Naqvi, S., Cole, T., Graham, J. M., Jr. <strong>Cole-Hughes macrocephaly syndrome and associated autistic manifestations.</strong> Am. J. Med. Genet. 94: 149-152, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982971</a>] [<a href="https://doi.org/10.1002/1096-8628(20000911)94:2<149::aid-ajmg7>3.0.co;2-#" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982971">Naqvi et al. (2000)</a> suggested that this may represent a recognizable syndrome within the autism behavioral phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10982971+1719811+9193390" 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="Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M. Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., Eng, C. <strong>Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.</strong> J. Med. Genet. 42: 318-321, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15805158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15805158</a>] [<a href="https://doi.org/10.1136/jmg.2004.024646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15805158">Butler et al. (2005)</a> studied 18 subjects from 3 to 18 years of age who had autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference, +4.0 SD). There were no features suggestive of Cowden syndrome (<a href="/entry/158350">158350</a>) except for pigmented macules on the glans penis of 1 boy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15805158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Herman, G. E., Butter, E., Enrile, B., Pastore, M., Prior, T. W., Sommer, A. <strong>Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly.</strong> Am. J. Med. Genet. 143A: 589-593, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17286265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17286265</a>] [<a href="https://doi.org/10.1002/ajmg.a.31619" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17286265">Herman et al. (2007)</a> reported 2 unrelated patients with macrocephaly and autism due to PTEN mutation. A 27-month-old affected girl had developmental delay, autistic features, and mild dysmorphism with broad forehead, mild hypertelorism, midface hypoplasia, depressed nasal bridge, and short nose. She did not resemble either of her parents. An unrelated 4-year-old boy with macrocephaly/autism syndrome was found to have an R130X mutation (<a href="/entry/601728#0007">601728.0007</a>), which had also been found in patients with Cowden syndrome and BRRS. This child inherited the mutation from his unaffected father. <a href="#6" class="mim-tip-reference" title="Herman, G. E., Butter, E., Enrile, B., Pastore, M., Prior, T. W., Sommer, A. <strong>Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly.</strong> Am. J. Med. Genet. 143A: 589-593, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17286265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17286265</a>] [<a href="https://doi.org/10.1002/ajmg.a.31619" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17286265">Herman et al. (2007)</a> noted that both children may develop further clinical manifestations of other PTEN-associated syndromes and emphasized that the second family was counseled on the possibility of increased tumor risk in the boy and the mutation-carrying father. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17286265" 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>Macrocephaly and Mental Retardation With Immunodeficiency</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Tsujita, Y., Mitsui-Sekinaka, K., Imai, K., Yeh, T.-W., Mitsuiki, N., Asano, T., Ohnishi, H., Kato, Z., Sekinaka, Y., Zaha, K., Kato, T., Okano, T., and 21 others. <strong>Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase delta syndrome-like immunodeficiency.</strong> J. Allergy Clin. Immun. 138: 1672-1680, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27426521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27426521</a>] [<a href="https://doi.org/10.1016/j.jaci.2016.03.055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27426521">Tsujita et al. (2016)</a> reported 2 unrelated Japanese children with macrocephaly and mental retardation associated with primary immunodeficiency. Common features included recurrent infections, fever, and lymphadenopathy; 1 patient had hepatosplenomegaly and transient pancytopenia. Both patients had opportunistic infections, i.e., pneumocystic pneumonia (PCP) and pulmonary aspergillosis, respectively. The immunologic defects varied. The first patient (P1) patient was suspected to have severe combined immunodeficiency, and laboratory studies showed lymphopenia, an inverted CD4/CD8 ratio, and low NK cells with normal or increased Ig levels. The other patient (P2) was given a diagnosis of common variable immunodeficiency, and laboratory studies showed hypogammaglobulinemia with normal B- and T-cell counts, but decreased numbers of memory B cells and class-switched B cells. Whole-exome sequencing of the patients identified a de novo heterozygous loss-of-function mutation in each patient (R233X, <a href="/entry/601728#0002">601728.0002</a> and c.41insGA, <a href="/entry/601728#0045">601728.0045</a>, respectively). Activated patient T cells showed decreased levels of PTEN protein, and T and B cells showed aberrant activation of the AKT (<a href="/entry/164730">164730</a>)/mTOR (<a href="/entry/601231">601231</a>) pathway compared to controls, suggesting that PTEN mutations cause increased PI3K signaling in lymphocytes. The findings were similar to that observed in patients with IMD14 (<a href="/entry/615513">615513</a>), who have activating mutations in the PIK3CD gene (<a href="/entry/602839">602839</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27426521" 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="#1" class="mim-tip-reference" title="Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M. Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., Eng, C. <strong>Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.</strong> J. Med. Genet. 42: 318-321, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15805158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15805158</a>] [<a href="https://doi.org/10.1136/jmg.2004.024646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15805158">Butler et al. (2005)</a> analyzed the PTEN gene in 18 subjects with autism spectrum disorders and macrocephaly. They identified heterozygosity for germline PTEN mutations in 3 boys: H93R (<a href="/entry/601728#0037">601728.0037</a>), D252G (<a href="/entry/601728#0038">601728.0038</a>), and F241S (<a href="/entry/601728#0039">601728.0039</a>), respectively. One mutation-positive boy had pigmented macules on his glans penis, but there were no other features or family history suggestive of CS or BRRS in these patients. No PTEN mutations were found in the 3 parents who were available for testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15805158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Herman, G. E., Butter, E., Enrile, B., Pastore, M., Prior, T. W., Sommer, A. <strong>Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly.</strong> Am. J. Med. Genet. 143A: 589-593, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17286265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17286265</a>] [<a href="https://doi.org/10.1002/ajmg.a.31619" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17286265">Herman et al. (2007)</a> reported 2 unrelated patients with macrocephaly and autism associated with heterozygous mutations in the PTEN gene (<a href="/entry/601728#0007">601728.0007</a> and <a href="/entry/610728#0040">610728.0040</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17286265" 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="O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others. <strong>Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.</strong> Science 338: 1619-1622, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1227764" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23160955">O'Roak et al. (2012)</a> identified 3 de novo mutations in the PTEN gene while sequencing 44 candidate genes among 2,446 autism spectrum disorder probands. There were 2 missense and 1 frameshift mutation identified. All 3 patients were macrocephalic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23160955" 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="#7" class="mim-tip-reference" title="Kwon, C.-H., Luikart, B. W., Powell, C. M., Zhou, J., Matheny, S. A., Zhang, W., Li, Y., Baker, S. J., Parada, L. F. <strong>Pten regulates neuronal arborization and social interaction in mice.</strong> Neuron 50: 377-388, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16675393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16675393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16675393[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2006.03.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16675393">Kwon et al. (2006)</a> found that mice with targeted inactivation of the Pten gene in differentiated neurons of the cerebral cortex and hippocampus demonstrated abnormal social interaction and exaggerated responses to sensory stimuli. The mice also showed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axon tracts with increased synapses. The findings suggested that Pten defects in mice can result in macrocephaly and autistic-like behavior. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16675393" 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="#10" class="mim-tip-reference" title="Page, D. T., Kuti, O. J., Prestia, C., Sur, M. <strong>Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior.</strong> Proc. Nat. Acad. Sci. 106: 1989-1994, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0804428106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19208814">Page et al. (2009)</a> showed that haploinsufficient Pten +/- mice were macrocephalic and that female, but not male, Pten +/- mice were impaired in social approach behavior. This phenotype was exacerbated in Pten +/- Slc6a4 (<a href="/entry/182138">182138</a>) +/- double-haploinsufficient mice. While increased brain size correlated with decreased sociability across these genotypes in females, within each genotype, increased brain size correlated with increased sociability, suggesting that epigenetic influences interact with genetic factors in influencing the phenotype. The findings suggested an interaction between 2 autism spectrum disorder candidate genes during brain development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19208814" 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="#3" class="mim-tip-reference" title="Clipperton-Allen, A. E., Page, D. T. <strong>Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests.</strong> Hum. Molec. Genet. 23: 3490-3505, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24497577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24497577</a>] [<a href="https://doi.org/10.1093/hmg/ddu057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24497577">Clipperton-Allen and Page (2014)</a> found that Pten +/- mice showed widespread brain overgrowth and deficits in social behavior. In addition, Pten +/- males showed repetitive behavior and abnormalities related to mood or anxiety, whereas Pten +/- females showed abnormal circadian activity and emotional learning. Conditional deletion of Pten in dopaminergic neurons resulted in abnormal social interactions similar to those found in Pten +/- mice. <a href="#4" class="mim-tip-reference" title="Clipperton-Allen, A. E., Page, D. T. <strong>Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.</strong> Genes Brain Behav. 14: 145-157, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25561290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25561290</a>] [<a href="https://doi.org/10.1111/gbb.12192" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25561290">Clipperton-Allen and Page (2015)</a> found that Pten +/- males showed reduced aggression, in addition to elevated repetitive behavior. <a href="#2" class="mim-tip-reference" title="Chen, Y., Huang, W.-C., Sejourne, J., Clipperton-Allen, A. E., Page, D. T. <strong>Pten mutations alter brain growth trajectory and allocation of cell types through elevated beta-catenin signaling.</strong> J. Neurosci. 35: 10252-10267, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26180201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26180201</a>] [<a href="https://doi.org/10.1523/JNEUROSCI.5272-14.2015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26180201">Chen et al. (2015)</a> found that haploinsufficiency in beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>), but not Mtor (<a href="/entry/601231">601231</a>), reduced cortical overgrowth in Pten +/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25561290+26180201+24497577" 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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Chen, Y., Huang, W.-C., Sejourne, J., Clipperton-Allen, A. E., Page, D. T.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26180201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26180201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26180201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1523/JNEUROSCI.5272-14.2015" target="_blank">Full Text</a>]
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<a id="Clipperton-Allen2014" class="mim-anchor"></a>
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Clipperton-Allen, A. E., Page, D. T.
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<strong>Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests.</strong>
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Hum. Molec. Genet. 23: 3490-3505, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24497577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24497577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24497577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddu057" target="_blank">Full Text</a>]
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Clipperton-Allen, A. E., Page, D. T.
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<strong>Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.</strong>
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Genes Brain Behav. 14: 145-157, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25561290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25561290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25561290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kwon, C.-H., Luikart, B. W., Powell, C. M., Zhou, J., Matheny, S. A., Zhang, W., Li, Y., Baker, S. J., Parada, L. F.
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<strong>Pten regulates neuronal arborization and social interaction in mice.</strong>
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Neuron 50: 377-388, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16675393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16675393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16675393[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=16675393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.neuron.2006.03.023" target="_blank">Full Text</a>]
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O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23160955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23160955</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23160955[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=23160955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1227764" target="_blank">Full Text</a>]
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Page, D. T., Kuti, O. J., Prestia, C., Sur, M.
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<strong>Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior.</strong>
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Proc. Nat. Acad. Sci. 106: 1989-1994, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19208814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19208814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19208814[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=19208814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0804428106" target="_blank">Full Text</a>]
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Stevenson, R. E., Schroer, R. J., Skinner, C., Fender, D., Simensen, R. J.
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<strong>Autism and macrocephaly.</strong>
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Lancet 349: 1744-1745, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9193390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9193390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9193390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/S0140-6736(05)62956-X" target="_blank">Full Text</a>]
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Tsujita, Y., Mitsui-Sekinaka, K., Imai, K., Yeh, T.-W., Mitsuiki, N., Asano, T., Ohnishi, H., Kato, Z., Sekinaka, Y., Zaha, K., Kato, T., Okano, T., and 21 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27426521/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27426521</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27426521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jaci.2016.03.055" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 03/02/2017
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Patricia A. Hartz - updated : 02/18/2016<br>Cassandra L. Kniffin - updated : 4/11/2007<br>Marla J. F. O'Neill - updated : 6/20/2005
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Sonja A. Rasmussen : 10/2/2000
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carol : 06/26/2018
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alopez : 03/06/2017<br>ckniffin : 03/02/2017<br>carol : 10/03/2016<br>mgross : 02/18/2016<br>carol : 2/18/2016<br>mgross : 2/17/2016<br>alopez : 1/25/2013<br>terry : 1/23/2013<br>terry : 9/20/2007<br>wwang : 4/13/2007<br>ckniffin : 4/11/2007<br>wwang : 6/27/2005<br>terry : 6/20/2005<br>carol : 10/20/2000<br>terry : 10/6/2000<br>carol : 10/2/2000
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<strong>ORPHA:</strong> 210548;
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<strong>DO:</strong> 0060867;
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10q23.31
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Macrocephaly/autism syndrome
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Autosomal dominant
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PTEN
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601728
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<p>A number sign (#) is used with this entry because of evidence that macrocephaly/autism syndrome is caused by heterozygous mutation in the PTEN gene (601728) on chromosome 10q23.</p><p>Heterozygous mutation in the PTEN gene can also cause Cowden syndrome (CWS1; 158350), which shows some overlapping features.</p>
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<p>Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (Herman et al., 2007). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (Tsujita et al., 2016). </p>
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<p>In the course of a clinical study of Sotos syndrome (117550), Cole and Hughes (1991) found that 6 of 79 probands who failed to fit that phenotype showed remarkable similarities to each other and to some of their first- and second-degree relatives. In addition to macrocephaly, affected individuals had typical facies characterized by square outline with frontal bossing, 'dished-out' midface, biparietal narrowing, and long philtrum. Birth weight and length were normal or near normal with subsequent obesity. Cole and Hughes (1991) were uncertain whether this represented a new entity or benign familial macrocephaly (153470). </p><p>Naqvi et al. (2000) reported 2 patients who had the same clinical features as the patients described by Cole and Hughes (1991) in addition to autistic characteristics with attention deficit disorder. The authors noted that the patients described by Cole and Hughes (1991) with adequate psychometric data had delays in language and social development much more prominent than delays in motor function, suggesting that some of these patients may have had autistic features. They also noted that Stevenson et al. (1997) had found progressive postnatal macrocephaly in 24% of 100 patients with autism and that 62% of such cases had a family history of macrocephaly. Naqvi et al. (2000) suggested that this may represent a recognizable syndrome within the autism behavioral phenotype. </p><p>Butler et al. (2005) studied 18 subjects from 3 to 18 years of age who had autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference, +4.0 SD). There were no features suggestive of Cowden syndrome (158350) except for pigmented macules on the glans penis of 1 boy. </p><p>Herman et al. (2007) reported 2 unrelated patients with macrocephaly and autism due to PTEN mutation. A 27-month-old affected girl had developmental delay, autistic features, and mild dysmorphism with broad forehead, mild hypertelorism, midface hypoplasia, depressed nasal bridge, and short nose. She did not resemble either of her parents. An unrelated 4-year-old boy with macrocephaly/autism syndrome was found to have an R130X mutation (601728.0007), which had also been found in patients with Cowden syndrome and BRRS. This child inherited the mutation from his unaffected father. Herman et al. (2007) noted that both children may develop further clinical manifestations of other PTEN-associated syndromes and emphasized that the second family was counseled on the possibility of increased tumor risk in the boy and the mutation-carrying father. </p><p><strong><em>Macrocephaly and Mental Retardation With Immunodeficiency</em></strong></p><p>
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Tsujita et al. (2016) reported 2 unrelated Japanese children with macrocephaly and mental retardation associated with primary immunodeficiency. Common features included recurrent infections, fever, and lymphadenopathy; 1 patient had hepatosplenomegaly and transient pancytopenia. Both patients had opportunistic infections, i.e., pneumocystic pneumonia (PCP) and pulmonary aspergillosis, respectively. The immunologic defects varied. The first patient (P1) patient was suspected to have severe combined immunodeficiency, and laboratory studies showed lymphopenia, an inverted CD4/CD8 ratio, and low NK cells with normal or increased Ig levels. The other patient (P2) was given a diagnosis of common variable immunodeficiency, and laboratory studies showed hypogammaglobulinemia with normal B- and T-cell counts, but decreased numbers of memory B cells and class-switched B cells. Whole-exome sequencing of the patients identified a de novo heterozygous loss-of-function mutation in each patient (R233X, 601728.0002 and c.41insGA, 601728.0045, respectively). Activated patient T cells showed decreased levels of PTEN protein, and T and B cells showed aberrant activation of the AKT (164730)/mTOR (601231) pathway compared to controls, suggesting that PTEN mutations cause increased PI3K signaling in lymphocytes. The findings were similar to that observed in patients with IMD14 (615513), who have activating mutations in the PIK3CD gene (602839). </p>
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<strong>Molecular Genetics</strong>
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<p>Butler et al. (2005) analyzed the PTEN gene in 18 subjects with autism spectrum disorders and macrocephaly. They identified heterozygosity for germline PTEN mutations in 3 boys: H93R (601728.0037), D252G (601728.0038), and F241S (601728.0039), respectively. One mutation-positive boy had pigmented macules on his glans penis, but there were no other features or family history suggestive of CS or BRRS in these patients. No PTEN mutations were found in the 3 parents who were available for testing. </p><p>Herman et al. (2007) reported 2 unrelated patients with macrocephaly and autism associated with heterozygous mutations in the PTEN gene (601728.0007 and 610728.0040). </p><p>O'Roak et al. (2012) identified 3 de novo mutations in the PTEN gene while sequencing 44 candidate genes among 2,446 autism spectrum disorder probands. There were 2 missense and 1 frameshift mutation identified. All 3 patients were macrocephalic. </p>
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<strong>Animal Model</strong>
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<p>Kwon et al. (2006) found that mice with targeted inactivation of the Pten gene in differentiated neurons of the cerebral cortex and hippocampus demonstrated abnormal social interaction and exaggerated responses to sensory stimuli. The mice also showed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axon tracts with increased synapses. The findings suggested that Pten defects in mice can result in macrocephaly and autistic-like behavior. </p><p>Page et al. (2009) showed that haploinsufficient Pten +/- mice were macrocephalic and that female, but not male, Pten +/- mice were impaired in social approach behavior. This phenotype was exacerbated in Pten +/- Slc6a4 (182138) +/- double-haploinsufficient mice. While increased brain size correlated with decreased sociability across these genotypes in females, within each genotype, increased brain size correlated with increased sociability, suggesting that epigenetic influences interact with genetic factors in influencing the phenotype. The findings suggested an interaction between 2 autism spectrum disorder candidate genes during brain development. </p><p>Clipperton-Allen and Page (2014) found that Pten +/- mice showed widespread brain overgrowth and deficits in social behavior. In addition, Pten +/- males showed repetitive behavior and abnormalities related to mood or anxiety, whereas Pten +/- females showed abnormal circadian activity and emotional learning. Conditional deletion of Pten in dopaminergic neurons resulted in abnormal social interactions similar to those found in Pten +/- mice. Clipperton-Allen and Page (2015) found that Pten +/- males showed reduced aggression, in addition to elevated repetitive behavior. Chen et al. (2015) found that haploinsufficiency in beta-catenin (CTNNB1; 116806), but not Mtor (601231), reduced cortical overgrowth in Pten +/- mice. </p>
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<strong>REFERENCES</strong>
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Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M. Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., Eng, C.
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<strong>Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.</strong>
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J. Med. Genet. 42: 318-321, 2005.
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[PubMed: 15805158]
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[Full Text: https://doi.org/10.1136/jmg.2004.024646]
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Chen, Y., Huang, W.-C., Sejourne, J., Clipperton-Allen, A. E., Page, D. T.
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<strong>Pten mutations alter brain growth trajectory and allocation of cell types through elevated beta-catenin signaling.</strong>
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J. Neurosci. 35: 10252-10267, 2015.
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[PubMed: 26180201]
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[Full Text: https://doi.org/10.1523/JNEUROSCI.5272-14.2015]
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Clipperton-Allen, A. E., Page, D. T.
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<strong>Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests.</strong>
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Hum. Molec. Genet. 23: 3490-3505, 2014.
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[PubMed: 24497577]
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[Full Text: https://doi.org/10.1093/hmg/ddu057]
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Clipperton-Allen, A. E., Page, D. T.
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<strong>Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.</strong>
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Genes Brain Behav. 14: 145-157, 2015.
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[PubMed: 25561290]
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[Full Text: https://doi.org/10.1111/gbb.12192]
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Cole, T. R. P., Hughes, H. E.
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<strong>Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome?</strong>
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Am. J. Med. Genet. 41: 115-124, 1991.
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[PubMed: 1719811]
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[Full Text: https://doi.org/10.1002/ajmg.1320410128]
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Herman, G. E., Butter, E., Enrile, B., Pastore, M., Prior, T. W., Sommer, A.
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<strong>Increasing knowledge of PTEN germline mutations: two additional patients with autism and macrocephaly.</strong>
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Am. J. Med. Genet. 143A: 589-593, 2007.
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[PubMed: 17286265]
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[Full Text: https://doi.org/10.1002/ajmg.a.31619]
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Kwon, C.-H., Luikart, B. W., Powell, C. M., Zhou, J., Matheny, S. A., Zhang, W., Li, Y., Baker, S. J., Parada, L. F.
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<strong>Pten regulates neuronal arborization and social interaction in mice.</strong>
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Neuron 50: 377-388, 2006.
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[PubMed: 16675393]
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[Full Text: https://doi.org/10.1016/j.neuron.2006.03.023]
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O'Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., Munson, J., Hiatt, J. B., and 14 others.
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Page, D. T., Kuti, O. J., Prestia, C., Sur, M.
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Stevenson, R. E., Schroer, R. J., Skinner, C., Fender, D., Simensen, R. J.
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Tsujita, Y., Mitsui-Sekinaka, K., Imai, K., Yeh, T.-W., Mitsuiki, N., Asano, T., Ohnishi, H., Kato, Z., Sekinaka, Y., Zaha, K., Kato, T., Okano, T., and 21 others.
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Cassandra L. Kniffin - updated : 03/02/2017<br>Patricia A. Hartz - updated : 02/18/2016<br>Cassandra L. Kniffin - updated : 4/11/2007<br>Marla J. F. O'Neill - updated : 6/20/2005
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