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Entry
- #162300 - MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B
- OMIM
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<span class="h4">#162300</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/162300"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS131100"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<div><a href="https://clinicaltrials.gov/search?cond=MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19539&Typ=Pat" title="Multiple endocrine neoplasia type 2B" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Multiple endocrine neoplas…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=906&Typ=Pat" title="Multiple endocrine neoplasia type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Multiple endocrine neoplas…&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1257/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247709" title="Multiple endocrine neoplasia type 2B" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Multiple endocrine neoplas…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=653" title="Multiple endocrine neoplasia type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Multiple endocrine neoplas…</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/09b8b399-2bcb-4c78-88ac-2582d772f6cc/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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:10016" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/162300" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:162300" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 61530001<br />
<strong>ICD10CM:</strong> E31.23<br />
<strong>ICD9CM:</strong> 258.03<br />
<strong>ORPHA:</strong> 247709, 653<br />
<strong>DO:</strong> 10016<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
162300
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MEN IIB<br />
NEUROMATA, MUCOSAL, WITH ENDOCRINE TUMORS<br />
WAGENMANN-FROBOESE SYNDROME<br />
MULTIPLE ENDOCRINE NEOPLASIA, TYPE III, FORMERLY; MEN3, FORMERLY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
MUCOSAL NEUROMA SYNDROME, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/158?start=-3&limit=10&highlight=158">
10q11.21
</a>
</span>
</td>
<td>
<span class="mim-font">
Multiple endocrine neoplasia IIB
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/162300"> 162300 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
RET
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164761"> 164761 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/162300" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS131100" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/162300" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/162300" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Marfanoid body habitus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836996&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836996</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001519" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001519</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001519" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001519</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1867873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867873</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001531" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001531</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001531" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001531</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coarse-appearing facies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834212&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834212</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pedunculated nodules on eyelid margins <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834213&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834213</a>]</span><br /> -
Eyelid and corneal neuromas <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834214</a>]</span><br /> -
Medullated corneal nerve fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834215&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834215</a>]</span><br /> -
Thickened, anteverted eyelid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834216&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834216</a>]</span><br /> -
Large, prominent eyebrow <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834217&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834217</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Neuromas of lips and tongue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834218</a>]</span><br /> -
Thick lips <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836543</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span><br /> -
High arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=c606b0119d4a894ebd5ee0242c136e29" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Palate,High-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=c606b0119d4a894ebd5ee0242c136e29&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Nodular goiter <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/419153005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">419153005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018023&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018023</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005994" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005994</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005994" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005994</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pectus excavatum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/391987005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">391987005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/391982004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">391982004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016842&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016842</a>, <a href="https://bioportal.bioontology.org/search?q=C2051831&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2051831</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000767" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000767</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000767" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000767</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Megacolon <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33995003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33995003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.3</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.39" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.39</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025160&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025160</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:6000852" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:6000852</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:6000852" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:6000852</a>]</span><br /> -
Colonic diverticulosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398050005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398050005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/733657002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">733657002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K57.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K57.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0012819&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0012819</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002253" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002253</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002253" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002253</a>]</span><br /> -
Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
Diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267060006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267060006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62315008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R19.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R19.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011991</a>, <a href="https://bioportal.bioontology.org/search?q=C2169706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2169706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span><br /> -
Ganglioneuroma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53801007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53801007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/116371000119107" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">116371000119107</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017075&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017075</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003005</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br /> -
Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br /> -
Lordosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61960001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61960001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249710008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249710008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187290008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187290008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0599412&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0599412</a>, <a href="https://bioportal.bioontology.org/search?q=C0024003&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024003</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003307</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003307</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Joint laxity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298203008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298203008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a>, <a href="https://bioportal.bioontology.org/search?q=C0086437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br /> -
Slipped capital femoral epiphyses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26460006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26460006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M93.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M93.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/732.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">732.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149887&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149887</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006461" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006461</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006461" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006461</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pes cavus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205091006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205091006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36755004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36755004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86900005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86900005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.73</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/754.71" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.71</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0728829&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728829</a>, <a href="https://bioportal.bioontology.org/search?q=C0039273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039273</a>, <a href="https://bioportal.bioontology.org/search?q=C2239098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Pes_Cavus-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Flushing attacks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805788&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805788</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Myopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/129565002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">129565002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G72.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M60-M63" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M60-M63</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/359.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">359.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003198" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003198</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003198" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003198</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Parathyroid hyperplasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9092004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9092004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E21.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271844&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271844</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008208" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008208</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008208" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008208</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEOPLASIA </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Ganglioneuroma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53801007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53801007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/116371000119107" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">116371000119107</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017075&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017075</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003005</a>]</span><br /> -
Pheochromocytoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85583005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85583005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302835009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302835009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0031511&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0031511</a>, <a href="https://bioportal.bioontology.org/search?q=C4551683&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551683</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002666" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002666</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0006748" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006748</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002666" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002666</a>]</span><br /> -
Medullary thyroid carcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1332275004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1332275004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255032005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255032005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238462&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238462</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002865" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002865</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002865" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002865</a>]</span><br /> -
Parathyroid disease rare <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1834219&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1834219</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Pentagastrin stimulation test <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/252210001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">252210001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0430136&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0430136</a>]</span><br /> -
Elevated calcitonin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1868394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1868394</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003528" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003528</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003528" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003528</a>]</span><br /> -
Increased urinary epinephrine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1868393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1868393</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003639</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Medullary thyroid cancer is aggressive and can occur in childhood<br /> -
Fifty percent of cases are sporadic<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the RET protooncogene (RET, <a href="/entry/164761#0013">164761.0013</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Multiple endocrine neoplasia
- <a href="/phenotypicSeries/PS131100">PS131100</a>
- 4 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/158?start=-3&limit=10&highlight=158"> 10q11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/171400"> Multiple endocrine neoplasia IIA </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/171400"> 171400 </a>
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<a href="/entry/164761"> RET </a>
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<a href="/entry/164761"> 164761 </a>
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<a href="/geneMap/10/158?start=-3&limit=10&highlight=158"> 10q11.21 </a>
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<a href="/entry/162300"> Multiple endocrine neoplasia IIB </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/162300"> 162300 </a>
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<a href="/entry/164761"> RET </a>
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<span class="mim-font">
<a href="/entry/164761"> 164761 </a>
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<a href="/geneMap/11/561?start=-3&limit=10&highlight=561"> 11q13.1 </a>
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<a href="/entry/131100"> Multiple endocrine neoplasia 1 </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/131100"> 131100 </a>
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<a href="/entry/613733"> MEN1 </a>
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<span class="mim-font">
<a href="/entry/613733"> 613733 </a>
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<a href="/geneMap/12/181?start=-3&limit=10&highlight=181"> 12p13.1 </a>
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<span class="mim-font">
<a href="/entry/610755"> Multiple endocrine neoplasia, type IV </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
<a href="/entry/610755"> 610755 </a>
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<a href="/entry/600778"> CDKN1B </a>
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<span class="mim-font">
<a href="/entry/600778"> 600778 </a>
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<p>A number sign (#) is used with this entry because of evidence that multiple endocrine neoplasia type IIB (MEN2B) is caused by heterozygous mutation in the RET gene (<a href="/entry/164761">164761</a>) on chromosome 10q11. Most patients (95%) carry a specific M918T mutation (<a href="/entry/164761#0013">164761.0013</a>) in exon 16 of the RET gene.</p>
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<p>Multiple endocrine neoplasia type IIB (MEN2B) is an autosomal dominant hamartoneoplastic syndrome characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, and thickened corneal nerves. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems (review by <a href="#34" class="mim-tip-reference" title="Morrison, P. J., Nevin, N. C. &lt;strong&gt;Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).&lt;/strong&gt; J. Med. Genet. 33: 779-782, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8880581/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8880581&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.33.9.779&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8880581">Morrison and Nevin, 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8880581" 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>For a discussion of genetic heterogeneity of multiple endocrine neoplasia (MEN), see MEN1 (<a href="/entry/131100">131100</a>).</p>
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<p><a href="#42" class="mim-tip-reference" title="Williams, E. D., Pollock, D. J. &lt;strong&gt;Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen&#x27;s disease.&lt;/strong&gt; J. Path. Bact. 91: 71-80, 1966.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4957444/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4957444&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/path.1700910109&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4957444">Williams and Pollock (1966)</a> described 2 unrelated patients with multiple true neuromas, pheochromocytoma and thyroid carcinoma. The thyroid cancer was of the medullary type (MTC) as in MEN2A. Although the association of pheochromocytoma with neurofibromatosis is well known, the nervous tumor is a true neuroma, i.e., consists mainly of nerve cells, in this condition. The patients sometimes have cafe-au-lait spots. The neuromas occur as pedunculated nodules on the eyelid margins, lips and tongue. The lips are diffusely hypertrophied. The father of one of Williams and Pollock's cases had very thick lips and eyelid and tongue lesions as did his daughters. He had a medullary thyroid cancer and died at age 38 after an abdominal operation, having had symptoms suggestive of pheochromocytoma. <a href="#38" class="mim-tip-reference" title="Schimke, R. N., Hartmann, W. H., Prout, T. E., Rimoin, D. L. &lt;strong&gt;Pheochromocytoma, medullary thyroid carcinoma and multiple neuromas.&lt;/strong&gt; New Eng. J. Med. 279: 1-7, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4968712/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4968712&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM196807042790101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4968712">Schimke et al. (1968)</a> also reported cases. <a href="#16" class="mim-tip-reference" title="Cunliffe, W. J., Black, M. M., Hall, R., Johnston, I. D. A., Hudgson, P., Shuster, S., Gudmundsson, T. V., Joplin, G. F., Williams, E. D., Woodhouse, N. J. Y., Galante, L., MacIntyre, I. &lt;strong&gt;A calcitonin-secreting thyroid carcinoma.&lt;/strong&gt; Lancet 292: 63-66, 1968. Note: Originally Volume II."None>Cunliffe et al. (1968)</a> demonstrated calcitonin-secretion in a medullary carcinoma of the thyroid. The patient was a 19-year-old girl with acne, features of Marfan syndrome, neuromas of tongue and eyelid, prominent lips, nodular goiter, pigmentation of hands, feet and circumoral area, proximal myopathy, loose motions, and flushing attacks. The features suggesting Marfan syndrome were high arched palate, pectus excavatum, bilateral pes cavus, high patella and scoliosis. Marfanoid habitus and pes cavus are striking features in most. Megacolon with plexus hyperplasia is a feature (<a href="#13" class="mim-tip-reference" title="Carney, J. A., Hayles, A. B. &lt;strong&gt;Alimentary tract manifestations of multiple endocrine neoplasia, type 2b.&lt;/strong&gt; Mayo Clin. Proc. 52: 543-548, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/895196/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;895196&lt;/a&gt;]" pmid="895196">Carney and Hayles, 1977</a>). Colonic diverticula also occur. Mucosal neuromas involve the lips, anterior tongue, conjunctiva and nasal and laryngeal mucosa. Medullated nerve fibers traverse the cornea. <a href="#3" class="mim-tip-reference" title="Bartlett, R. C., Bean, L. R., Mandelstam, P. &lt;strong&gt;Hereditary study of neuroendocrine dysplasia in six generations. (Abstract)&lt;/strong&gt; International Association for Dental Research Annual Meeting, San Francisco, Calif. 1968. P. 36."None>Bartlett et al. (1968)</a> described affected persons in 6 generations. Prophylactic thyroidectomy should be performed when the phenotype is recognized (<a href="#43" class="mim-tip-reference" title="Wolfe, H. J., Melvin, K. E. W., Cervi-Skinner, S. J., Al Saadi, A. A., Juliar, J. F., Jackson, C. E., Tashjian, A. H., Jr. &lt;strong&gt;C-cell hyperplasia preceding medullary thyroid carcinoma.&lt;/strong&gt; New Eng. J. Med. 289: 437-441, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4587234/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4587234&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197308302890901&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4587234">Wolfe et al., 1973</a>). In addition to histaminase, DOPA decarboxylase is high in medullary carcinoma of the thyroid (<a href="#1" class="mim-tip-reference" title="Atkins, F. L., Beaven, M. A., Keiser, H. R. &lt;strong&gt;DOPA decarboxylase in medullary carcinoma of the thyroid.&lt;/strong&gt; New Eng. J. Med. 289: 545-548, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4146664/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4146664&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197309132891101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4146664">Atkins et al., 1973</a>). The latter enzyme is found in pheochromocytomas also. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4957444+895196+4587234+4968712+4146664" 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="#11" class="mim-tip-reference" title="Carney, J. A., Go, V. L. W., Sizemore, G. W., Hayles, A. B. &lt;strong&gt;Alimentary-tract ganglioneuromatosis: a major component of the syndrome of multiple endocrine neoplasia, type 2b.&lt;/strong&gt; New Eng. J. Med. 295: 1287-1291, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/980061/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;980061&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197612022952304&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="980061">Carney et al. (1976)</a> and <a href="#19" class="mim-tip-reference" title="Dyck, P. J., Carney, J. A., Sizemore, G. W., Okazaki, H., Brimijoin, W. S., Lambert, E. H. &lt;strong&gt;Multiple endocrine neoplasia, type 2b: phenotype recognition; neurological features and their pathological basis.&lt;/strong&gt; Ann. Neurol. 6: 302-314, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/554522/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;554522&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410060404&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="554522">Dyck et al. (1979)</a> described a kindred with 7 affected persons in 3 generations. In contrast to MEN2A, no parathyroid disease was found in any of them. The authors proposed the designation 'multiple endocrine neoplasia, type 2b.' <a href="#14" class="mim-tip-reference" title="Carney, J. A., Roth, S. I., Heath, H., III, Sizemore, G. W., Hayles, A. B. &lt;strong&gt;The parathyroid glands in multiple endocrine neoplasia type 2b.&lt;/strong&gt; Am. J. Path. 99: 387-398, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7377288/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7377288&lt;/a&gt;]" pmid="7377288">Carney et al. (1980)</a> confirmed the lack of clinically important involvement of the parathyroids in this disorder. <a href="#30" class="mim-tip-reference" title="Kullberg, B. J., Nieuwenhuijzen Kruseman, A. C. &lt;strong&gt;Multiple endocrine neoplasia type 2b with a good prognosis.&lt;/strong&gt; Arch. Intern. Med. 147: 1125-1127, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2884942/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2884942&lt;/a&gt;]" pmid="2884942">Kullberg and Nieuwenhuijzen Kruseman (1987)</a> described a patient who was known to have had liver metastases of medullary carcinoma of the thyroid for at least 22 years. Other features illustrating an indolent course of the disorder were displayed by affected members of this family. Derangement of esophageal motility with an achalasia-type clinical picture may be a leading problem (<a href="#6" class="mim-tip-reference" title="Baylin, S. B. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Baltimore, Md. 4/22/1989."None>Baylin, 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=980061+554522+7377288+2884942" 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="#21" class="mim-tip-reference" title="Fryns, J. P., Chrzanowska, K. &lt;strong&gt;Mucosal neuromata syndrome (MEN type IIb (III)).&lt;/strong&gt; J. Med. Genet. 25: 703-706, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2906373/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2906373&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.25.10.703&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2906373">Fryns and Chrzanowska (1988)</a> gave a review. Mutation in a gene controlling a paracrine or an autocrine growth factor seemed a possibility in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2906373" 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="#34" class="mim-tip-reference" title="Morrison, P. J., Nevin, N. C. &lt;strong&gt;Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).&lt;/strong&gt; J. Med. Genet. 33: 779-782, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8880581/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8880581&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.33.9.779&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8880581">Morrison and Nevin (1996)</a> presented a review of this syndrome. They used the term Wagenmann-Froboese syndrome, because <a href="#41" class="mim-tip-reference" title="Wagenmann, A. &lt;strong&gt;Multiple neurome des auges und der Zunge.&lt;/strong&gt; Ber. Dtsch. Ophthal. 43: 282-285, 1922."None>Wagenmann (1922)</a> and <a href="#20" class="mim-tip-reference" title="Froboese, C. &lt;strong&gt;Das aus markhaltigen nervenfascern bestehende gangliezellenlose echte neurom in rankenformzugleich ein beitrag zu den nervosen Geschwulsten der zunge und des augenlides.&lt;/strong&gt; Virchows Arch. A Path. Anat. 240: 312-327, 1923."None>Froboese (1923)</a> initially described this disorder. Thyroid carcinoma and multiple mucosal neuromata occur in virtually all affected persons. Neoplasias of enteric ganglia were found in more than 40% of patients; pheochromocytoma in 50%; and marfanoid habitus in 75%. The absence of mucosal neuromata in persons with MEN2A is the main criterion for differential diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8880581" 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>Enlarged nerves of the gastrointestinal tract (ganglioneuromatosis), often with megacolon, is a feature of MEN2B; corneal nerve thickening (medullated corneal nerve fibers) is a comparable feature, as are mucosal neuromas. <a href="#29" class="mim-tip-reference" title="Kane, L. A., Tsai, M. S., Gharib, H., Khosla, S., Robertson, D. M., Schaid, D. J., Honchel, R., Thibodeau, S. N. &lt;strong&gt;Familial medullary thyroid cancer and prominent corneal nerves: clinical and genetic analysis.&lt;/strong&gt; J. Clin. Endocr. Metab. 80: 289-293, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7829628/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7829628&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1210/jcem.80.1.7829628&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7829628">Kane et al. (1995)</a> described an unusual kindred in which medullary thyroid carcinoma was associated with corneal nerve thickening without other aspects of the multiple endocrine neoplasia syndromes. The grandfather and 1 daughter, both of whom had corneal nerve thickening, had medullary thyroid carcinoma, and a daughter of that daughter had both corneal nerve thickening and C-cell hyperplasia. Three adults in the middle generation had corneal nerve thickening only. DNA sequence analysis revealed no mutations in exon 10 or 11, or in exon 16 of the RET gene, regions where mutations had been described for MEN2A and MEN2B, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829628" 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>Clinical Variability</em></strong></p><p>
<a href="#17" class="mim-tip-reference" title="Dennehy, P. J., Feldman, G. L., Kambouris, M., O&#x27;Malley, E. R., Sanders, C. Y., Jackson, C. E. &lt;strong&gt;Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B.&lt;/strong&gt; Am. J. Ophthal. 120: 456-461, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7573303/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7573303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0002-9394(14)72659-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7573303">Dennehy et al. (1995)</a> reported a 2-generation family in which a mother and her 2 children had prominent corneal nerves and lesions of the tongue resembling neuromas, but had no evidence of endocrine abnormalities. Targeted screening excluded the RET M918T mutation (<a href="/entry/164761#0013">164761.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573303" 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="#24" class="mim-tip-reference" title="Gordon, C. M., Majzoub, J. A., Marsh, D. J., Mulliken, J. B., Ponder, B. A. J., Robinson, B. G., Eng, C. &lt;strong&gt;Four cases of mucosal neuroma syndrome: multiple endocrine neoplasm 2B or not 2B?&lt;/strong&gt; J. Clin. Endocr. Metab. 83: 17-20, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9435410/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9435410&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1210/jcem.83.1.4504&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9435410">Gordon et al. (1998)</a> reported 4 unrelated patients with a pure mucosal neuroma syndrome that presented as a partial MEN2B phenotype, but without medullary thyroid carcinoma, other endocrine tumors, or germline or somatic RET mutations. Three patients presented in the teenage years and one at age 5 years with multiple unilateral neuromas affecting the facial mucosa, including the mouth, tongue, eyes, nose, and lips. One patient had neuromas affecting multiple branches of the trigeminal nerve. Two patients had medullated corneal nerve fibers, but no Lisch nodules. Extensive endocrine workup in all 4 patients showed no abnormalities. Prophylactic thyroidectomy was performed in 1 patient, but histology showed no evidence of C-cell hyperplasia or tumor nodules. None of the patients or tumor tissues carried the RET M918T mutation (<a href="/entry/164761#0013">164761.0013</a>), and 3 patients studied did not have mutations in other selected RET exons. <a href="#24" class="mim-tip-reference" title="Gordon, C. M., Majzoub, J. A., Marsh, D. J., Mulliken, J. B., Ponder, B. A. J., Robinson, B. G., Eng, C. &lt;strong&gt;Four cases of mucosal neuroma syndrome: multiple endocrine neoplasm 2B or not 2B?&lt;/strong&gt; J. Clin. Endocr. Metab. 83: 17-20, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9435410/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9435410&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1210/jcem.83.1.4504&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9435410">Gordon et al. (1998)</a> concluded that pure mucosal neuroma syndrome does not appear to be a forme fruste of MEN2B at the genetic level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9435410" 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="#23" class="mim-tip-reference" title="Gomez, J. M., Biarnes, J., Volpini, V., Marti, T. &lt;strong&gt;Neuromas and prominent corneal nerves without MEN 2B.&lt;/strong&gt; Ann. Endocr. 59: 492-494, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10189992/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10189992&lt;/a&gt;]" pmid="10189992">Gomez et al. (1998)</a> reported a mother and daughter with multiple mucosal neuromas and visible corneal nerves. Neither had a marfanoid habitus, and endocrine workup was normal, and the RET M918T mutation was not found. The authors concluded that familial multiple mucosal neuromas is a distinct entity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10189992" 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="#39" class="mim-tip-reference" title="Spyer, G., Ellard, S., Turnpenny, P. D., Hattersley, A. T., Vaidya, B. &lt;strong&gt;Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management.&lt;/strong&gt; Thyroid 16: 605-608, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16839263/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16839263&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1089/thy.2006.16.605&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16839263">Spyer et al. (2006)</a> reported a 13-year-old girl who presented with photophobia and was noted to have prominent corneal nerve fibers. She also had many features of MEN2B, including thick lips, multiple bilateral mucosal neuromas, a marfanoid habitus, and high-arched palate. Extensive endocrine workup revealed no abnormalities, but prophylactic thyroidectomy was performed. Histologic examination of the thyroid showed no evidence of medullary thyroid carcinoma or C-cell hyperplasia. Direct sequencing of exons 1-20 of the RET gene showed no mutations. She remained well over 18 years of follow-up. <a href="#39" class="mim-tip-reference" title="Spyer, G., Ellard, S., Turnpenny, P. D., Hattersley, A. T., Vaidya, B. &lt;strong&gt;Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management.&lt;/strong&gt; Thyroid 16: 605-608, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16839263/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16839263&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1089/thy.2006.16.605&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16839263">Spyer et al. (2006)</a> concluded that patients with features of the mucosal neuroma syndrome do not need to have a thyroidectomy, but should be followed for possible endocrine abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16839263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Babovic-Vuksanovic, D., Messiaen, L., Nagel, C., Brems, H., Scheithauer, B., Denayer, E., Mao, R., Sciot, R., Janowski, K. M., Schuhmann, M. U., Claes, K., Beert, E., Garrity, J. A., Spinner, R. J., Stemmer-Rachamimov, A., Gavrilova, R., Van Calenbergh, F., Mautner, V., Legius, E. &lt;strong&gt;Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.&lt;/strong&gt; Europ. J. Hum. Genet. 20: 618-625, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22258529/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22258529&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22258529[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2011.275&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22258529">Babovic-Vuksanovic et al. (2012)</a> reported 4 unrelated females with a similar constellation of physical features, including marfanoid habitus, coarse facial features, and multiple painful subcutaneous neurofibromas and nodules of the peripheral nerves occurring all over the body. All presented in the teenage or young adult years (range, 13-24 years) with clinical sequelae of the tumors. Two had orbital soft tissue swelling and proptosis/ptosis due to tumors of the corneal or trigeminal nerves, resulting in unilateral loss of vision in 1 patient. The other 2 patients presented with hemiparesis, and 1 also had lumbosacral pain due to multiple spinal nerve tumors. Histology showed neurofibromas with abundant mucin. All had a history of or later developed multiple painful subcutaneous nodules that were shown to be neurofibromas with abundant mucin. Tumors occurred in the head and neck region, spinal cord, trunk, and limbs. Other more variable features included pectus excavatum, scoliosis, and keloid scars. None had Lisch nodules, axillary or inguinal freckling, or cafe au lait spots. Two patients had evidence of a neuronal migration defect in the brain, with schizencephaly, but only 1 patient had seizures and learning disabilities. One patient had a severe axonal and demyelinating polyneuropathy. None had a family history of a similar disorder, and mutations in multiple candidate genes, including NF1 (<a href="/entry/613113">613113</a>), NF2 (<a href="/entry/607379">607379</a>), SMARCB1 (<a href="/entry/601607">601607</a>), RET, and PTEN (<a href="/entry/601728">601728</a>), were excluded in 2 patients. <a href="#2" class="mim-tip-reference" title="Babovic-Vuksanovic, D., Messiaen, L., Nagel, C., Brems, H., Scheithauer, B., Denayer, E., Mao, R., Sciot, R., Janowski, K. M., Schuhmann, M. U., Claes, K., Beert, E., Garrity, J. A., Spinner, R. J., Stemmer-Rachamimov, A., Gavrilova, R., Van Calenbergh, F., Mautner, V., Legius, E. &lt;strong&gt;Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.&lt;/strong&gt; Europ. J. Hum. Genet. 20: 618-625, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22258529/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22258529&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22258529[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ejhg.2011.275&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22258529">Babovic-Vuksanovic et al. (2012)</a> noted the phenotypic similarities to MEN2B and to mucosal neuroma syndrome, but concluded that the unusual findings of a developmental brain anomaly and nonmucosal nerve neurofibromas in their patients may represent a new condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22258529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p><a href="#28" class="mim-tip-reference" title="Jackson, C. E., Norum, R. A., O&#x27;Neal, L. W., Nikolai, T. F., Delaney, J. P. &lt;strong&gt;Linkage between MEN2B and chromosome 10 markers linked to MEN2A. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 43: A147, 1988."None>Jackson et al. (1988)</a> found evidence suggesting that MEN3 (MEN2B) maps to chromosome 10, probably in the same region as MEN2A (<a href="/entry/171400">171400</a>). It is possible that MEN2A and MEN2B are allelic disorders; if indeed such is the case, there would be every justification for calling them MEN2A and MEN2B rather than MEN2 and MEN3. <a href="#36" class="mim-tip-reference" title="Norum, R. A. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Detroit, Mich. 5/1989."None>Norum (1989)</a> presented compelling evidence that MEN3 is allelic to MEN2: both mapped to chromosome 10 near the centromere and are on the same side of the RBP3 gene (<a href="/entry/180290">180290</a>). <a href="#31" class="mim-tip-reference" title="Lairmore, T. C., Howe, J. R., Korte, J. A., Dilley, W. G., Aine, L., Aine, E., Wells, S. A., Jr., Donis-Keller, H. &lt;strong&gt;Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A.&lt;/strong&gt; Genomics 9: 181-192, 1991. Note: Erratum: Genomics 10: 514 only, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1672289/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1672289&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0888-7543(91)90237-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1672289">Lairmore et al. (1991)</a> presented evidence that the MEN2B locus maps in the pericentric region of chromosome 10. They found no evidence for linkage genetic heterogeneity among families with medullary thyroid carcinoma, MEN2B, or MEN2A. By genetic linkage analysis, <a href="#22" class="mim-tip-reference" title="Gardner, E., Papi, L., Easton, D. F., Cummings, T., Jackson, C. E., Kaplan, M., Love, D. R., Mole, S. E., Moore, J. K., Mulligan, L. M., Norum, R. A., Ponder, M. A., Reichlin, S., Stall, G., Telenius, H., Telenius-Berg, M., Tunnacliffe, A., Ponder, B. A. J. &lt;strong&gt;Genetic linkage studies map the multiple endocrine neoplasia type 2 loci to a small interval on chromosome 10q11.2.&lt;/strong&gt; Hum. Molec. Genet. 2: 241-246, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8098977/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8098977&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/2.3.241&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8098977">Gardner et al. (1993)</a> demonstrated that the MEN2B locus is flanked by D10S141 and RBP3, proximally and distally, respectively; both markers are located in 10q11.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8098977+1672289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<p>In 9 unrelated MEN2B patients, <a href="#27" class="mim-tip-reference" title="Hofstra, R. M. W., Landsvater, R. M., Ceccherini, I., Stulp, R. P., Stelwagen, T., Luo, Y., Pasini, B., Hoppener, J. W. M., Ploos van Amstel, H. K., Romeo, G., Lips, C. J. M., Buys, C. H. C. M. &lt;strong&gt;A mutation in the RET protooncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma.&lt;/strong&gt; Nature 367: 375-376, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7906866/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7906866&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/367375a0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7906866">Hofstra et al. (1994)</a> identified a substitution of a threonine for a methionine in the tyrosine kinase domain of the RET protein (M918T; <a href="/entry/164761#0013">164761.0013</a>). The M918T mutation in the tyrosine kinase domain is the only RET mutation identified in cases of MEN2B (<a href="#7" class="mim-tip-reference" title="Bongarzone, I., Vigano, E., Alberti, L., Borrello, M. G., Pasini, B., Greco, A., Mondellini, P., Smith, D. P., Ponder, B. A. J., Romeo, G., Pierotti, M. A. &lt;strong&gt;Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand GDNF stimulation.&lt;/strong&gt; Oncogene 16: 2295-2301, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9620546/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9620546&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.onc.1201759&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9620546">Bongarzone et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7906866+9620546" 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="Carlson, K. M., Bracamontes, J., Jackson, C. E., Clark, R., Lacroix, A., Wells, S. A., Jr., Goodfellow, P. J. &lt;strong&gt;Parent-of-origin effects in multiple endocrine neoplasia type 2B.&lt;/strong&gt; Am. J. Hum. Genet. 55: 1076-1082, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7977365/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7977365&lt;/a&gt;]" pmid="7977365">Carlson et al. (1994)</a> estimated that 50% of cases of MEN2B arise de novo. A single identical point mutation in the catalytic core of the tyrosine kinase domain of RET has been found to be associated with both inherited and de novo MEN2B. <a href="#9" class="mim-tip-reference" title="Carlson, K. M., Bracamontes, J., Jackson, C. E., Clark, R., Lacroix, A., Wells, S. A., Jr., Goodfellow, P. J. &lt;strong&gt;Parent-of-origin effects in multiple endocrine neoplasia type 2B.&lt;/strong&gt; Am. J. Hum. Genet. 55: 1076-1082, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7977365/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7977365&lt;/a&gt;]" pmid="7977365">Carlson et al. (1994)</a> analyzed 25 cases of de novo MEN2B in order to determine the parental origin of the mutated RET allele. In all cases, the new mutation was of paternal origin. They observed a distortion of sex ratio in both de novo MEN2B patients and the affected offspring of MEN2B-transmitting males. Specifically, as pointed out by <a href="#37" class="mim-tip-reference" title="Sapienza, C. &lt;strong&gt;Parental origin effects, genome imprinting, and sex-ratio distortion: double or nothing? (Editorial)&lt;/strong&gt; Am. J. Hum. Genet. 55: 1073-1075, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7977364/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7977364&lt;/a&gt;]" pmid="7977364">Sapienza (1994)</a>, the report by <a href="#9" class="mim-tip-reference" title="Carlson, K. M., Bracamontes, J., Jackson, C. E., Clark, R., Lacroix, A., Wells, S. A., Jr., Goodfellow, P. J. &lt;strong&gt;Parent-of-origin effects in multiple endocrine neoplasia type 2B.&lt;/strong&gt; Am. J. Hum. Genet. 55: 1076-1082, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7977365/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7977365&lt;/a&gt;]" pmid="7977365">Carlson et al. (1994)</a> and that of another group includes 45 females and 24 males with de novo MEN2B. These results suggested a differential susceptibility of RET mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7977365+7977364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Clinical Management</strong>
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<p>Prophylactic total thyroidectomy before the age of 4 years was proposed for children with this disorder (<a href="#33" class="mim-tip-reference" title="Morrison, P. J., Hadden, D. R., Hughes, A. E., Russell, C. F. J., Nevin, N. C. &lt;strong&gt;Gene probe analysis in an informative family with the MEN2A syndrome. Improvement in carrier risk estimations.&lt;/strong&gt; Quart. J. Med. 78: 597-603, 1991."None>Morrison et al., 1991</a>; <a href="#40" class="mim-tip-reference" title="Utiger, R. D. &lt;strong&gt;Medullary thyroid carcinoma, genes and the prevention of cancer.&lt;/strong&gt; New Eng. J. Med. 331: 870-871, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7915823/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7915823&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199409293311309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7915823">Utiger, 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7915823" 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>Because the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma in MEN2B is ill-defined, <a href="#32" class="mim-tip-reference" title="Leboulleux, S., Travagli, J. P., Caillou, B., Laplanche, A., Bidart, J. M., Schlumberger, M., Baudin, E. &lt;strong&gt;Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course.&lt;/strong&gt; Cancer 94: 44-50, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11815959/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11815959&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/cncr.10205&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11815959">Leboulleux et al. (2002)</a> reviewed 18 patients in a single-center retrospective study: 9 men and 9 women with a mean age of 13 years at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 of the RET gene was found in all 16 patients in whom it was investigated. At diagnosis, 2 patients had stage I MTC, 15 had stage III, and 1 had stage IV disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. <a href="#32" class="mim-tip-reference" title="Leboulleux, S., Travagli, J. P., Caillou, B., Laplanche, A., Bidart, J. M., Schlumberger, M., Baudin, E. &lt;strong&gt;Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course.&lt;/strong&gt; Cancer 94: 44-50, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11815959/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11815959&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/cncr.10205&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11815959">Leboulleux et al. (2002)</a> concluded that the study confirmed the need for early treatment of MTC in patients with the MEN2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN2B syndrome was, however, not more aggressive than sporadic MTC or MTC occurring in other familial syndromes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11815959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Baum1972" class="mim-tip-reference" title="Baum, J. L., Adler, M. E. &lt;strong&gt;Pheochromocytoma, medullary thyroid carcinoma, multiple mucosal neuroma: a variant of the syndrome.&lt;/strong&gt; Arch. Ophthal. 87: 574-584, 1972.">Baum and Adler (1972)</a>; <a href="#Baylin1970" class="mim-tip-reference" title="Baylin, S. B., Beaven, M. A., Engelman, K., Sjoerdsma, A. &lt;strong&gt;Elevated histaminase activity in medullary carcinoma of the thyroid gland.&lt;/strong&gt; New Eng. J. Med. 283: 1239-1244, 1970.">Baylin et al. (1970)</a>; <a href="#Braley1954" class="mim-tip-reference" title="Braley, A. E. &lt;strong&gt;Medullated corneal nerves and plexiform neuroma associated with pheochromocytoma.&lt;/strong&gt; Trans. Am. Ophthal. Soc. 52: 189-197, 1954.">Braley (1954)</a>; <a href="#Carlson1994" class="mim-tip-reference" title="Carlson, K. M., Dou, S., Chi, D., Scavarda, N., Toshima, K., Jackson, C. E., Wells, S. A., Jr., Goodfellow, P. J., Donis-Keller, H. &lt;strong&gt;Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.&lt;/strong&gt; Proc. Nat. Acad. Sci. 91: 1579-1583, 1994.">Carlson
et al. (1994)</a>; <a href="#Carney1981" class="mim-tip-reference" title="Carney, J. A., Hayles, A. B., Pearse, A. G. E., Perry, H. O., Sizemore, G. W. &lt;strong&gt;Abnormal cutaneous innervation in multiple endocrine neoplasia, type 2b.&lt;/strong&gt; Ann. Intern. Med. 94: 362-363, 1981.">Carney et al. (1981)</a>; <a href="#Carney1976" class="mim-tip-reference" title="Carney, J. A., Sizemore, G. W., Lovestedt, S. A. &lt;strong&gt;Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b.&lt;/strong&gt; Oral Surg. 41: 739-752, 1976.">Carney et al. (1976)</a>; <a href="#DeSchryver-Kecskemeti1983" class="mim-tip-reference" title="DeSchryver-Kecskemeti, K., Clouse, R. E., Goldstein, M. N., Gersell, D., O&#x27;Neal, L. &lt;strong&gt;Intestinal ganglioneuromatosis: a manifestation of overproduction of nerve growth factor?&lt;/strong&gt; New Eng. J. Med. 308: 635-639, 1983.">DeSchryver-Kecskemeti et al. (1983)</a>; <a href="#Gorlin1972" class="mim-tip-reference" title="Gorlin, R. J., Mirkin, B. L. &lt;strong&gt;Multiple mucosal neuromas, pheochromocytoma, medullary carcinoma of the thyroid and marfanoid body build with muscle wasting: syndrome of hyperplasia and neoplasia of neural crest derivatives; a unitarian concept.&lt;/strong&gt; Z. Kinderheilk. 113: 313-321, 1972.">Gorlin and Mirkin (1972)</a>; <a href="#Gorlin1968" class="mim-tip-reference" title="Gorlin, R. J., Sedano, H. O., Vickers, R. A., Cervenka, J. &lt;strong&gt;Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid--a syndrome.&lt;/strong&gt; Cancer 22: 293-299, 1968.">Gorlin
et al. (1968)</a>; <a href="#Moyes1977" class="mim-tip-reference" title="Moyes, C. D., Alexander, F. W. &lt;strong&gt;Mucosal neuroma syndrome presenting in a neonate.&lt;/strong&gt; Dev. Med. Child Neurol. 19: 518-521, 1977.">Moyes and Alexander (1977)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Atkins1973" class="mim-anchor"></a>
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Atkins, F. L., Beaven, M. A., Keiser, H. R.
<strong>DOPA decarboxylase in medullary carcinoma of the thyroid.</strong>
New Eng. J. Med. 289: 545-548, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4146664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4146664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4146664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197309132891101" target="_blank">Full Text</a>]
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<a id="Babovic-Vuksanovic2012" class="mim-anchor"></a>
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Babovic-Vuksanovic, D., Messiaen, L., Nagel, C., Brems, H., Scheithauer, B., Denayer, E., Mao, R., Sciot, R., Janowski, K. M., Schuhmann, M. U., Claes, K., Beert, E., Garrity, J. A., Spinner, R. J., Stemmer-Rachamimov, A., Gavrilova, R., Van Calenbergh, F., Mautner, V., Legius, E.
<strong>Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.</strong>
Europ. J. Hum. Genet. 20: 618-625, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22258529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22258529</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22258529[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=22258529" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ejhg.2011.275" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
<a id="Bartlett1968" class="mim-anchor"></a>
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<p class="mim-text-font">
Bartlett, R. C., Bean, L. R., Mandelstam, P.
<strong>Hereditary study of neuroendocrine dysplasia in six generations. (Abstract)</strong>
International Association for Dental Research Annual Meeting, San Francisco, Calif. 1968. P. 36.
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<a id="4" class="mim-anchor"></a>
<a id="Baum1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Baum, J. L., Adler, M. E.
<strong>Pheochromocytoma, medullary thyroid carcinoma, multiple mucosal neuroma: a variant of the syndrome.</strong>
Arch. Ophthal. 87: 574-584, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4623875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4623875</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4623875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archopht.1972.01000020576016" target="_blank">Full Text</a>]
</p>
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<a id="5" class="mim-anchor"></a>
<a id="Baylin1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Baylin, S. B., Beaven, M. A., Engelman, K., Sjoerdsma, A.
<strong>Elevated histaminase activity in medullary carcinoma of the thyroid gland.</strong>
New Eng. J. Med. 283: 1239-1244, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4990961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4990961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4990961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197012032832301" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
<a id="Baylin1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Baylin, S. B.
<strong>Personal Communication.</strong>
Baltimore, Md. 4/22/1989.
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<a id="7" class="mim-anchor"></a>
<a id="Bongarzone1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bongarzone, I., Vigano, E., Alberti, L., Borrello, M. G., Pasini, B., Greco, A., Mondellini, P., Smith, D. P., Ponder, B. A. J., Romeo, G., Pierotti, M. A.
<strong>Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand GDNF stimulation.</strong>
Oncogene 16: 2295-2301, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9620546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9620546</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9620546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/sj.onc.1201759" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
<a id="Braley1954" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Braley, A. E.
<strong>Medullated corneal nerves and plexiform neuroma associated with pheochromocytoma.</strong>
Trans. Am. Ophthal. Soc. 52: 189-197, 1954.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13274423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13274423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13274423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="9" class="mim-anchor"></a>
<a id="Carlson1994" class="mim-anchor"></a>
<div class="">
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<strong>Parent-of-origin effects in multiple endocrine neoplasia type 2B.</strong>
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Carlson, K. M., Dou, S., Chi, D., Scavarda, N., Toshima, K., Jackson, C. E., Wells, S. A., Jr., Goodfellow, P. J., Donis-Keller, H.
<strong>Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.</strong>
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[<a href="https://doi.org/10.1073/pnas.91.4.1579" target="_blank">Full Text</a>]
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<strong>Alimentary-tract ganglioneuromatosis: a major component of the syndrome of multiple endocrine neoplasia, type 2b.</strong>
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[<a href="https://doi.org/10.1056/NEJM197612022952304" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.7326/0003-4819-94-3-362" target="_blank">Full Text</a>]
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Carney, J. A., Roth, S. I., Heath, H., III, Sizemore, G. W., Hayles, A. B.
<strong>The parathyroid glands in multiple endocrine neoplasia type 2b.</strong>
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<strong>Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b.</strong>
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[<a href="https://doi.org/10.1016/0030-4220(76)90187-0" target="_blank">Full Text</a>]
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<strong>A calcitonin-secreting thyroid carcinoma.</strong>
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[<a href="https://doi.org/10.1016/s0002-9394(14)72659-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM198303173081106" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410060404" target="_blank">Full Text</a>]
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<strong>Das aus markhaltigen nervenfascern bestehende gangliezellenlose echte neurom in rankenformzugleich ein beitrag zu den nervosen Geschwulsten der zunge und des augenlides.</strong>
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[<a href="https://doi.org/10.1136/jmg.25.10.703" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/2.3.241" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1210/jcem.83.1.4504" target="_blank">Full Text</a>]
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<strong>Multiple mucosal neuromas, pheochromocytoma, medullary carcinoma of the thyroid and marfanoid body build with muscle wasting: syndrome of hyperplasia and neoplasia of neural crest derivatives; a unitarian concept.</strong>
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[<a href="https://doi.org/10.1007/BF00440310" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1097-0142(196808)22:2&lt;293::aid-cncr2820220206&gt;3.0.co;2-r" target="_blank">Full Text</a>]
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Hofstra, R. M. W., Landsvater, R. M., Ceccherini, I., Stulp, R. P., Stelwagen, T., Luo, Y., Pasini, B., Hoppener, J. W. M., Ploos van Amstel, H. K., Romeo, G., Lips, C. J. M., Buys, C. H. C. M.
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[<a href="https://doi.org/10.1038/367375a0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1210/jcem.80.1.7829628" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(91)90237-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/cncr.10205" target="_blank">Full Text</a>]
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<a id="34" class="mim-anchor"></a>
<a id="Morrison1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morrison, P. J., Nevin, N. C.
<strong>Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).</strong>
J. Med. Genet. 33: 779-782, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8880581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8880581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8880581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.33.9.779" target="_blank">Full Text</a>]
</p>
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<a id="35" class="mim-anchor"></a>
<a id="Moyes1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Moyes, C. D., Alexander, F. W.
<strong>Mucosal neuroma syndrome presenting in a neonate.</strong>
Dev. Med. Child Neurol. 19: 518-521, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/892250/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">892250</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=892250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1469-8749.1977.tb07947.x" target="_blank">Full Text</a>]
</p>
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<a id="36" class="mim-anchor"></a>
<a id="Norum1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Norum, R. A.
<strong>Personal Communication.</strong>
Detroit, Mich. 5/1989.
</p>
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<a id="37" class="mim-anchor"></a>
<a id="Sapienza1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sapienza, C.
<strong>Parental origin effects, genome imprinting, and sex-ratio distortion: double or nothing? (Editorial)</strong>
Am. J. Hum. Genet. 55: 1073-1075, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7977364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7977364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7977364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
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<li>
<a id="38" class="mim-anchor"></a>
<a id="Schimke1968" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schimke, R. N., Hartmann, W. H., Prout, T. E., Rimoin, D. L.
<strong>Pheochromocytoma, medullary thyroid carcinoma and multiple neuromas.</strong>
New Eng. J. Med. 279: 1-7, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4968712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4968712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4968712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM196807042790101" target="_blank">Full Text</a>]
</p>
</div>
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<a id="39" class="mim-anchor"></a>
<a id="Spyer2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Spyer, G., Ellard, S., Turnpenny, P. D., Hattersley, A. T., Vaidya, B.
<strong>Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management.</strong>
Thyroid 16: 605-608, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16839263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16839263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16839263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1089/thy.2006.16.605" target="_blank">Full Text</a>]
</p>
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<li>
<a id="40" class="mim-anchor"></a>
<a id="Utiger1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Utiger, R. D.
<strong>Medullary thyroid carcinoma, genes and the prevention of cancer.</strong>
New Eng. J. Med. 331: 870-871, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7915823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7915823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7915823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199409293311309" target="_blank">Full Text</a>]
</p>
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<li>
<a id="41" class="mim-anchor"></a>
<a id="Wagenmann1922" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wagenmann, A.
<strong>Multiple neurome des auges und der Zunge.</strong>
Ber. Dtsch. Ophthal. 43: 282-285, 1922.
</p>
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<li>
<a id="42" class="mim-anchor"></a>
<a id="Williams1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Williams, E. D., Pollock, D. J.
<strong>Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen's disease.</strong>
J. Path. Bact. 91: 71-80, 1966.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4957444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4957444</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4957444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/path.1700910109" target="_blank">Full Text</a>]
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<li>
<a id="43" class="mim-anchor"></a>
<a id="Wolfe1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wolfe, H. J., Melvin, K. E. W., Cervi-Skinner, S. J., Al Saadi, A. A., Juliar, J. F., Jackson, C. E., Tashjian, A. H., Jr.
<strong>C-cell hyperplasia preceding medullary thyroid carcinoma.</strong>
New Eng. J. Med. 289: 437-441, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4587234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4587234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4587234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197308302890901" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 8/22/2012
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<span class="mim-text-font">
Marla J. F. O'Neill - updated : 2/12/2007<br>Victor A. McKusick - updated : 2/25/2002<br>Victor A. McKusick - updated : 7/10/1998<br>Iosif W. Lurie - updated : 12/4/1996<br>Alan F. Scott - updated : 2/7/1996
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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Victor A. McKusick : 6/2/1986
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carol : 06/05/2018
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carol : 10/13/2016<br>alopez : 02/24/2016<br>carol : 9/19/2013<br>carol : 8/22/2012<br>terry : 8/22/2012<br>ckniffin : 8/22/2012<br>terry : 5/25/2012<br>carol : 10/14/2010<br>terry : 10/14/2010<br>terry : 1/30/2009<br>carol : 5/9/2007<br>wwang : 2/12/2007<br>carol : 3/1/2002<br>cwells : 3/1/2002<br>terry : 2/25/2002<br>carol : 7/9/1999<br>terry : 5/3/1999<br>carol : 7/15/1998<br>terry : 7/10/1998<br>carol : 6/15/1998<br>mark : 10/8/1997<br>jamie : 12/4/1996<br>jamie : 12/4/1996<br>terry : 4/17/1996<br>mark : 2/7/1996<br>carol : 3/19/1995<br>mimadm : 12/2/1994<br>davew : 8/17/1994<br>warfield : 4/21/1994<br>carol : 4/26/1993<br>carol : 8/13/1992
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<h3>
<span class="mim-font">
<strong>#</strong> 162300
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<h3>
<span class="mim-font">
MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B
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<span class="mim-font">
<em>Alternative titles; symbols</em>
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<span class="mim-font">
MEN IIB<br />
NEUROMATA, MUCOSAL, WITH ENDOCRINE TUMORS<br />
WAGENMANN-FROBOESE SYNDROME<br />
MULTIPLE ENDOCRINE NEOPLASIA, TYPE III, FORMERLY; MEN3, FORMERLY
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<p>
<span class="mim-font">
Other entities represented in this entry:
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<span class="h3 mim-font">
MUCOSAL NEUROMA SYNDROME, INCLUDED
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<strong>SNOMEDCT:</strong> 61530001; &nbsp;
<strong>ICD10CM:</strong> E31.23; &nbsp;
<strong>ICD9CM:</strong> 258.03; &nbsp;
<strong>ORPHA:</strong> 247709, 653; &nbsp;
<strong>DO:</strong> 10016; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<th>
Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
10q11.21
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Multiple endocrine neoplasia IIB
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162300
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Autosomal dominant
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3
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<span class="mim-font">
RET
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<span class="mim-font">
164761
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<span class="mim-font">
<strong>TEXT</strong>
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<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that multiple endocrine neoplasia type IIB (MEN2B) is caused by heterozygous mutation in the RET gene (164761) on chromosome 10q11. Most patients (95%) carry a specific M918T mutation (164761.0013) in exon 16 of the RET gene.</p>
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<strong>Description</strong>
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<p>Multiple endocrine neoplasia type IIB (MEN2B) is an autosomal dominant hamartoneoplastic syndrome characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuromas, and thickened corneal nerves. Most affected individuals have characteristic physical features, including full lips, thickened eyelids, high-arched palate, and marfanoid habitus. Other more variable features include skeletal anomalies and gastrointestinal problems (review by Morrison and Nevin, 1996). </p><p>For a discussion of genetic heterogeneity of multiple endocrine neoplasia (MEN), see MEN1 (131100).</p>
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<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
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<p>Williams and Pollock (1966) described 2 unrelated patients with multiple true neuromas, pheochromocytoma and thyroid carcinoma. The thyroid cancer was of the medullary type (MTC) as in MEN2A. Although the association of pheochromocytoma with neurofibromatosis is well known, the nervous tumor is a true neuroma, i.e., consists mainly of nerve cells, in this condition. The patients sometimes have cafe-au-lait spots. The neuromas occur as pedunculated nodules on the eyelid margins, lips and tongue. The lips are diffusely hypertrophied. The father of one of Williams and Pollock's cases had very thick lips and eyelid and tongue lesions as did his daughters. He had a medullary thyroid cancer and died at age 38 after an abdominal operation, having had symptoms suggestive of pheochromocytoma. Schimke et al. (1968) also reported cases. Cunliffe et al. (1968) demonstrated calcitonin-secretion in a medullary carcinoma of the thyroid. The patient was a 19-year-old girl with acne, features of Marfan syndrome, neuromas of tongue and eyelid, prominent lips, nodular goiter, pigmentation of hands, feet and circumoral area, proximal myopathy, loose motions, and flushing attacks. The features suggesting Marfan syndrome were high arched palate, pectus excavatum, bilateral pes cavus, high patella and scoliosis. Marfanoid habitus and pes cavus are striking features in most. Megacolon with plexus hyperplasia is a feature (Carney and Hayles, 1977). Colonic diverticula also occur. Mucosal neuromas involve the lips, anterior tongue, conjunctiva and nasal and laryngeal mucosa. Medullated nerve fibers traverse the cornea. Bartlett et al. (1968) described affected persons in 6 generations. Prophylactic thyroidectomy should be performed when the phenotype is recognized (Wolfe et al., 1973). In addition to histaminase, DOPA decarboxylase is high in medullary carcinoma of the thyroid (Atkins et al., 1973). The latter enzyme is found in pheochromocytomas also. </p><p>Carney et al. (1976) and Dyck et al. (1979) described a kindred with 7 affected persons in 3 generations. In contrast to MEN2A, no parathyroid disease was found in any of them. The authors proposed the designation 'multiple endocrine neoplasia, type 2b.' Carney et al. (1980) confirmed the lack of clinically important involvement of the parathyroids in this disorder. Kullberg and Nieuwenhuijzen Kruseman (1987) described a patient who was known to have had liver metastases of medullary carcinoma of the thyroid for at least 22 years. Other features illustrating an indolent course of the disorder were displayed by affected members of this family. Derangement of esophageal motility with an achalasia-type clinical picture may be a leading problem (Baylin, 1989). </p><p>Fryns and Chrzanowska (1988) gave a review. Mutation in a gene controlling a paracrine or an autocrine growth factor seemed a possibility in this disorder. </p><p>Morrison and Nevin (1996) presented a review of this syndrome. They used the term Wagenmann-Froboese syndrome, because Wagenmann (1922) and Froboese (1923) initially described this disorder. Thyroid carcinoma and multiple mucosal neuromata occur in virtually all affected persons. Neoplasias of enteric ganglia were found in more than 40% of patients; pheochromocytoma in 50%; and marfanoid habitus in 75%. The absence of mucosal neuromata in persons with MEN2A is the main criterion for differential diagnosis. </p><p>Enlarged nerves of the gastrointestinal tract (ganglioneuromatosis), often with megacolon, is a feature of MEN2B; corneal nerve thickening (medullated corneal nerve fibers) is a comparable feature, as are mucosal neuromas. Kane et al. (1995) described an unusual kindred in which medullary thyroid carcinoma was associated with corneal nerve thickening without other aspects of the multiple endocrine neoplasia syndromes. The grandfather and 1 daughter, both of whom had corneal nerve thickening, had medullary thyroid carcinoma, and a daughter of that daughter had both corneal nerve thickening and C-cell hyperplasia. Three adults in the middle generation had corneal nerve thickening only. DNA sequence analysis revealed no mutations in exon 10 or 11, or in exon 16 of the RET gene, regions where mutations had been described for MEN2A and MEN2B, respectively. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Dennehy et al. (1995) reported a 2-generation family in which a mother and her 2 children had prominent corneal nerves and lesions of the tongue resembling neuromas, but had no evidence of endocrine abnormalities. Targeted screening excluded the RET M918T mutation (164761.0013). </p><p>Gordon et al. (1998) reported 4 unrelated patients with a pure mucosal neuroma syndrome that presented as a partial MEN2B phenotype, but without medullary thyroid carcinoma, other endocrine tumors, or germline or somatic RET mutations. Three patients presented in the teenage years and one at age 5 years with multiple unilateral neuromas affecting the facial mucosa, including the mouth, tongue, eyes, nose, and lips. One patient had neuromas affecting multiple branches of the trigeminal nerve. Two patients had medullated corneal nerve fibers, but no Lisch nodules. Extensive endocrine workup in all 4 patients showed no abnormalities. Prophylactic thyroidectomy was performed in 1 patient, but histology showed no evidence of C-cell hyperplasia or tumor nodules. None of the patients or tumor tissues carried the RET M918T mutation (164761.0013), and 3 patients studied did not have mutations in other selected RET exons. Gordon et al. (1998) concluded that pure mucosal neuroma syndrome does not appear to be a forme fruste of MEN2B at the genetic level. </p><p>Gomez et al. (1998) reported a mother and daughter with multiple mucosal neuromas and visible corneal nerves. Neither had a marfanoid habitus, and endocrine workup was normal, and the RET M918T mutation was not found. The authors concluded that familial multiple mucosal neuromas is a distinct entity. </p><p>Spyer et al. (2006) reported a 13-year-old girl who presented with photophobia and was noted to have prominent corneal nerve fibers. She also had many features of MEN2B, including thick lips, multiple bilateral mucosal neuromas, a marfanoid habitus, and high-arched palate. Extensive endocrine workup revealed no abnormalities, but prophylactic thyroidectomy was performed. Histologic examination of the thyroid showed no evidence of medullary thyroid carcinoma or C-cell hyperplasia. Direct sequencing of exons 1-20 of the RET gene showed no mutations. She remained well over 18 years of follow-up. Spyer et al. (2006) concluded that patients with features of the mucosal neuroma syndrome do not need to have a thyroidectomy, but should be followed for possible endocrine abnormalities. </p><p>Babovic-Vuksanovic et al. (2012) reported 4 unrelated females with a similar constellation of physical features, including marfanoid habitus, coarse facial features, and multiple painful subcutaneous neurofibromas and nodules of the peripheral nerves occurring all over the body. All presented in the teenage or young adult years (range, 13-24 years) with clinical sequelae of the tumors. Two had orbital soft tissue swelling and proptosis/ptosis due to tumors of the corneal or trigeminal nerves, resulting in unilateral loss of vision in 1 patient. The other 2 patients presented with hemiparesis, and 1 also had lumbosacral pain due to multiple spinal nerve tumors. Histology showed neurofibromas with abundant mucin. All had a history of or later developed multiple painful subcutaneous nodules that were shown to be neurofibromas with abundant mucin. Tumors occurred in the head and neck region, spinal cord, trunk, and limbs. Other more variable features included pectus excavatum, scoliosis, and keloid scars. None had Lisch nodules, axillary or inguinal freckling, or cafe au lait spots. Two patients had evidence of a neuronal migration defect in the brain, with schizencephaly, but only 1 patient had seizures and learning disabilities. One patient had a severe axonal and demyelinating polyneuropathy. None had a family history of a similar disorder, and mutations in multiple candidate genes, including NF1 (613113), NF2 (607379), SMARCB1 (601607), RET, and PTEN (601728), were excluded in 2 patients. Babovic-Vuksanovic et al. (2012) noted the phenotypic similarities to MEN2B and to mucosal neuroma syndrome, but concluded that the unusual findings of a developmental brain anomaly and nonmucosal nerve neurofibromas in their patients may represent a new condition. </p>
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<h4>
<span class="mim-font">
<strong>Mapping</strong>
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</h4>
</div>
<span class="mim-text-font">
<p>Jackson et al. (1988) found evidence suggesting that MEN3 (MEN2B) maps to chromosome 10, probably in the same region as MEN2A (171400). It is possible that MEN2A and MEN2B are allelic disorders; if indeed such is the case, there would be every justification for calling them MEN2A and MEN2B rather than MEN2 and MEN3. Norum (1989) presented compelling evidence that MEN3 is allelic to MEN2: both mapped to chromosome 10 near the centromere and are on the same side of the RBP3 gene (180290). Lairmore et al. (1991) presented evidence that the MEN2B locus maps in the pericentric region of chromosome 10. They found no evidence for linkage genetic heterogeneity among families with medullary thyroid carcinoma, MEN2B, or MEN2A. By genetic linkage analysis, Gardner et al. (1993) demonstrated that the MEN2B locus is flanked by D10S141 and RBP3, proximally and distally, respectively; both markers are located in 10q11.2. </p>
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<div>
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<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In 9 unrelated MEN2B patients, Hofstra et al. (1994) identified a substitution of a threonine for a methionine in the tyrosine kinase domain of the RET protein (M918T; 164761.0013). The M918T mutation in the tyrosine kinase domain is the only RET mutation identified in cases of MEN2B (Bongarzone et al., 1998). </p><p>Carlson et al. (1994) estimated that 50% of cases of MEN2B arise de novo. A single identical point mutation in the catalytic core of the tyrosine kinase domain of RET has been found to be associated with both inherited and de novo MEN2B. Carlson et al. (1994) analyzed 25 cases of de novo MEN2B in order to determine the parental origin of the mutated RET allele. In all cases, the new mutation was of paternal origin. They observed a distortion of sex ratio in both de novo MEN2B patients and the affected offspring of MEN2B-transmitting males. Specifically, as pointed out by Sapienza (1994), the report by Carlson et al. (1994) and that of another group includes 45 females and 24 males with de novo MEN2B. These results suggested a differential susceptibility of RET mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Prophylactic total thyroidectomy before the age of 4 years was proposed for children with this disorder (Morrison et al., 1991; Utiger, 1994). </p><p>Because the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma in MEN2B is ill-defined, Leboulleux et al. (2002) reviewed 18 patients in a single-center retrospective study: 9 men and 9 women with a mean age of 13 years at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 of the RET gene was found in all 16 patients in whom it was investigated. At diagnosis, 2 patients had stage I MTC, 15 had stage III, and 1 had stage IV disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. Leboulleux et al. (2002) concluded that the study confirmed the need for early treatment of MTC in patients with the MEN2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN2B syndrome was, however, not more aggressive than sporadic MTC or MTC occurring in other familial syndromes. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Baum and Adler (1972); Baylin et al. (1970); Braley (1954); Carlson
et al. (1994); Carney et al. (1981); Carney et al. (1976);
DeSchryver-Kecskemeti et al. (1983); Gorlin and Mirkin (1972); Gorlin
et al. (1968); Moyes and Alexander (1977)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
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</p>
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Babovic-Vuksanovic, D., Messiaen, L., Nagel, C., Brems, H., Scheithauer, B., Denayer, E., Mao, R., Sciot, R., Janowski, K. M., Schuhmann, M. U., Claes, K., Beert, E., Garrity, J. A., Spinner, R. J., Stemmer-Rachamimov, A., Gavrilova, R., Van Calenbergh, F., Mautner, V., Legius, E.
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<strong>Alimentary-tract ganglioneuromatosis: a major component of the syndrome of multiple endocrine neoplasia, type 2b.</strong>
New Eng. J. Med. 295: 1287-1291, 1976.
[PubMed: 980061]
[Full Text: https://doi.org/10.1056/NEJM197612022952304]
</p>
</li>
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<p class="mim-text-font">
Carney, J. A., Hayles, A. B., Pearse, A. G. E., Perry, H. O., Sizemore, G. W.
<strong>Abnormal cutaneous innervation in multiple endocrine neoplasia, type 2b.</strong>
Ann. Intern. Med. 94: 362-363, 1981.
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</p>
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<p class="mim-text-font">
Carney, J. A., Hayles, A. B.
<strong>Alimentary tract manifestations of multiple endocrine neoplasia, type 2b.</strong>
Mayo Clin. Proc. 52: 543-548, 1977.
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</p>
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<p class="mim-text-font">
Carney, J. A., Roth, S. I., Heath, H., III, Sizemore, G. W., Hayles, A. B.
<strong>The parathyroid glands in multiple endocrine neoplasia type 2b.</strong>
Am. J. Path. 99: 387-398, 1980.
[PubMed: 7377288]
</p>
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<li>
<p class="mim-text-font">
Carney, J. A., Sizemore, G. W., Lovestedt, S. A.
<strong>Mucosal ganglioneuromatosis, medullary thyroid carcinoma, and pheochromocytoma: multiple endocrine neoplasia, type 2b.</strong>
Oral Surg. 41: 739-752, 1976.
[PubMed: 1063979]
[Full Text: https://doi.org/10.1016/0030-4220(76)90187-0]
</p>
</li>
<li>
<p class="mim-text-font">
Cunliffe, W. J., Black, M. M., Hall, R., Johnston, I. D. A., Hudgson, P., Shuster, S., Gudmundsson, T. V., Joplin, G. F., Williams, E. D., Woodhouse, N. J. Y., Galante, L., MacIntyre, I.
<strong>A calcitonin-secreting thyroid carcinoma.</strong>
Lancet 292: 63-66, 1968. Note: Originally Volume II.
</p>
</li>
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<p class="mim-text-font">
Dennehy, P. J., Feldman, G. L., Kambouris, M., O'Malley, E. R., Sanders, C. Y., Jackson, C. E.
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Am. J. Ophthal. 120: 456-461, 1995.
[PubMed: 7573303]
[Full Text: https://doi.org/10.1016/s0002-9394(14)72659-5]
</p>
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DeSchryver-Kecskemeti, K., Clouse, R. E., Goldstein, M. N., Gersell, D., O'Neal, L.
<strong>Intestinal ganglioneuromatosis: a manifestation of overproduction of nerve growth factor?</strong>
New Eng. J. Med. 308: 635-639, 1983.
[PubMed: 6131380]
[Full Text: https://doi.org/10.1056/NEJM198303173081106]
</p>
</li>
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<p class="mim-text-font">
Dyck, P. J., Carney, J. A., Sizemore, G. W., Okazaki, H., Brimijoin, W. S., Lambert, E. H.
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Ann. Neurol. 6: 302-314, 1979.
[PubMed: 554522]
[Full Text: https://doi.org/10.1002/ana.410060404]
</p>
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<li>
<p class="mim-text-font">
Froboese, C.
<strong>Das aus markhaltigen nervenfascern bestehende gangliezellenlose echte neurom in rankenformzugleich ein beitrag zu den nervosen Geschwulsten der zunge und des augenlides.</strong>
Virchows Arch. A Path. Anat. 240: 312-327, 1923.
</p>
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<p class="mim-text-font">
Fryns, J. P., Chrzanowska, K.
<strong>Mucosal neuromata syndrome (MEN type IIb (III)).</strong>
J. Med. Genet. 25: 703-706, 1988.
[PubMed: 2906373]
[Full Text: https://doi.org/10.1136/jmg.25.10.703]
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Gardner, E., Papi, L., Easton, D. F., Cummings, T., Jackson, C. E., Kaplan, M., Love, D. R., Mole, S. E., Moore, J. K., Mulligan, L. M., Norum, R. A., Ponder, M. A., Reichlin, S., Stall, G., Telenius, H., Telenius-Berg, M., Tunnacliffe, A., Ponder, B. A. J.
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[PubMed: 8098977]
[Full Text: https://doi.org/10.1093/hmg/2.3.241]
</p>
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<p class="mim-text-font">
Gomez, J. M., Biarnes, J., Volpini, V., Marti, T.
<strong>Neuromas and prominent corneal nerves without MEN 2B.</strong>
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</p>
</li>
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<p class="mim-text-font">
Gordon, C. M., Majzoub, J. A., Marsh, D. J., Mulliken, J. B., Ponder, B. A. J., Robinson, B. G., Eng, C.
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[Full Text: https://doi.org/10.1210/jcem.83.1.4504]
</p>
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<p class="mim-text-font">
Gorlin, R. J., Mirkin, B. L.
<strong>Multiple mucosal neuromas, pheochromocytoma, medullary carcinoma of the thyroid and marfanoid body build with muscle wasting: syndrome of hyperplasia and neoplasia of neural crest derivatives; a unitarian concept.</strong>
Z. Kinderheilk. 113: 313-321, 1972.
[PubMed: 4649671]
[Full Text: https://doi.org/10.1007/BF00440310]
</p>
</li>
<li>
<p class="mim-text-font">
Gorlin, R. J., Sedano, H. O., Vickers, R. A., Cervenka, J.
<strong>Multiple mucosal neuromas, pheochromocytoma and medullary carcinoma of the thyroid--a syndrome.</strong>
Cancer 22: 293-299, 1968.
[PubMed: 5660196]
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</p>
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<li>
<p class="mim-text-font">
Hofstra, R. M. W., Landsvater, R. M., Ceccherini, I., Stulp, R. P., Stelwagen, T., Luo, Y., Pasini, B., Hoppener, J. W. M., Ploos van Amstel, H. K., Romeo, G., Lips, C. J. M., Buys, C. H. C. M.
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</p>
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Jackson, C. E., Norum, R. A., O'Neal, L. W., Nikolai, T. F., Delaney, J. P.
<strong>Linkage between MEN2B and chromosome 10 markers linked to MEN2A. (Abstract)</strong>
Am. J. Hum. Genet. 43: A147, 1988.
</p>
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Kane, L. A., Tsai, M. S., Gharib, H., Khosla, S., Robertson, D. M., Schaid, D. J., Honchel, R., Thibodeau, S. N.
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</p>
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Kullberg, B. J., Nieuwenhuijzen Kruseman, A. C.
<strong>Multiple endocrine neoplasia type 2b with a good prognosis.</strong>
Arch. Intern. Med. 147: 1125-1127, 1987.
[PubMed: 2884942]
</p>
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<li>
<p class="mim-text-font">
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<strong>Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A.</strong>
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[PubMed: 1672289]
[Full Text: https://doi.org/10.1016/0888-7543(91)90237-9]
</p>
</li>
<li>
<p class="mim-text-font">
Leboulleux, S., Travagli, J. P., Caillou, B., Laplanche, A., Bidart, J. M., Schlumberger, M., Baudin, E.
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</p>
</li>
<li>
<p class="mim-text-font">
Morrison, P. J., Hadden, D. R., Hughes, A. E., Russell, C. F. J., Nevin, N. C.
<strong>Gene probe analysis in an informative family with the MEN2A syndrome. Improvement in carrier risk estimations.</strong>
Quart. J. Med. 78: 597-603, 1991.
</p>
</li>
<li>
<p class="mim-text-font">
Morrison, P. J., Nevin, N. C.
<strong>Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).</strong>
J. Med. Genet. 33: 779-782, 1996.
[PubMed: 8880581]
[Full Text: https://doi.org/10.1136/jmg.33.9.779]
</p>
</li>
<li>
<p class="mim-text-font">
Moyes, C. D., Alexander, F. W.
<strong>Mucosal neuroma syndrome presenting in a neonate.</strong>
Dev. Med. Child Neurol. 19: 518-521, 1977.
[PubMed: 892250]
[Full Text: https://doi.org/10.1111/j.1469-8749.1977.tb07947.x]
</p>
</li>
<li>
<p class="mim-text-font">
Norum, R. A.
<strong>Personal Communication.</strong>
Detroit, Mich. 5/1989.
</p>
</li>
<li>
<p class="mim-text-font">
Sapienza, C.
<strong>Parental origin effects, genome imprinting, and sex-ratio distortion: double or nothing? (Editorial)</strong>
Am. J. Hum. Genet. 55: 1073-1075, 1994.
[PubMed: 7977364]
</p>
</li>
<li>
<p class="mim-text-font">
Schimke, R. N., Hartmann, W. H., Prout, T. E., Rimoin, D. L.
<strong>Pheochromocytoma, medullary thyroid carcinoma and multiple neuromas.</strong>
New Eng. J. Med. 279: 1-7, 1968.
[PubMed: 4968712]
[Full Text: https://doi.org/10.1056/NEJM196807042790101]
</p>
</li>
<li>
<p class="mim-text-font">
Spyer, G., Ellard, S., Turnpenny, P. D., Hattersley, A. T., Vaidya, B.
<strong>Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management.</strong>
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[PubMed: 16839263]
[Full Text: https://doi.org/10.1089/thy.2006.16.605]
</p>
</li>
<li>
<p class="mim-text-font">
Utiger, R. D.
<strong>Medullary thyroid carcinoma, genes and the prevention of cancer.</strong>
New Eng. J. Med. 331: 870-871, 1994.
[PubMed: 7915823]
[Full Text: https://doi.org/10.1056/NEJM199409293311309]
</p>
</li>
<li>
<p class="mim-text-font">
Wagenmann, A.
<strong>Multiple neurome des auges und der Zunge.</strong>
Ber. Dtsch. Ophthal. 43: 282-285, 1922.
</p>
</li>
<li>
<p class="mim-text-font">
Williams, E. D., Pollock, D. J.
<strong>Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen&#x27;s disease.</strong>
J. Path. Bact. 91: 71-80, 1966.
[PubMed: 4957444]
[Full Text: https://doi.org/10.1002/path.1700910109]
</p>
</li>
<li>
<p class="mim-text-font">
Wolfe, H. J., Melvin, K. E. W., Cervi-Skinner, S. J., Al Saadi, A. A., Juliar, J. F., Jackson, C. E., Tashjian, A. H., Jr.
<strong>C-cell hyperplasia preceding medullary thyroid carcinoma.</strong>
New Eng. J. Med. 289: 437-441, 1973.
[PubMed: 4587234]
[Full Text: https://doi.org/10.1056/NEJM197308302890901]
</p>
</li>
</ol>
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Cassandra L. Kniffin - updated : 8/22/2012<br>Marla J. F. O&#x27;Neill - updated : 2/12/2007<br>Victor A. McKusick - updated : 2/25/2002<br>Victor A. McKusick - updated : 7/10/1998<br>Iosif W. Lurie - updated : 12/4/1996<br>Alan F. Scott - updated : 2/7/1996
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