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- #259050 - PRIMROSE SYNDROME; PRIMS
- OMIM
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<span class="h4">#259050</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/259050"><strong>Clinical Synopsis</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=PRIMROSE SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=2735&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK570205/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=259050[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3042" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/4ecffddb-bbf9-4d84-8d2a-3cb06b0a81d9/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 726709001<br />
<strong>ORPHA:</strong> 3042<br />
">ICD+</a>
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259050
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</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
PRIMROSE SYNDROME; PRIMS
</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">
OSSIFIED EAR CARTILAGES WITH MENTAL DEFICIENCY, MUSCLE WASTING, AND BONY CHANGES
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/564?start=-3&limit=10&highlight=564">
3q13.31
</a>
</span>
</td>
<td>
<span class="mim-font">
Primrose syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259050"> 259050 </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">
ZBTB20
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606025"> 606025 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/259050" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/259050" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/259050" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Weight above the 90th percentile <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012181&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012181</a>]</span><br /> -
Truncal obesity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248311001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248311001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551560&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551560</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001956" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001956</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001956" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001956</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">
- Diminishing growth rate (in 1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936692&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936692</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Brachycephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13649004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13649004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221356&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221356</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000248" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000248</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000248" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000248</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9ccc4d161e106e4d5543286323f007ce" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Brachycephaly-Large-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9ccc4d161e106e4d5543286323f007ce&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Midface hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853242&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853242</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Midface_Retrusion-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9&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 /> -
Wide forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Forehead,Broad-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00&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 /> -
Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Large jaw <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4280644&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4280644</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0040309" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040309</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040309" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040309</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Ossification of pinnae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1408806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1408806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005103" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005103</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005103" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005103</a>]</span><br /> -
Large pinnae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850189&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850189</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</a>]</span><br /> -
Superiorly displaced ears <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850190&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850190</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008541</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008541</a>]</span><br /> -
Hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C3887873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887873</a>, <a href="https://bioportal.bioontology.org/search?q=C2029884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2029884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</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">
- Posterior polar cataracts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850191&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850191</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001115" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001115</a>]</span><br /> -
Downslanting palpebral fissures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246800008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246800008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423110&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423110</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000494" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000494</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000494" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000494</a>]</span><br /> -
Deep-set eyes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246923005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246923005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000490</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=08eb099548b91270db09ad79e8e75da3" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eye,Deeply_Set-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=08eb099548b91270db09ad79e8e75da3&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 /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Prominent lower lip <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839739&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839739</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000179</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000179</a>]</span><br /> -
Small mouth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14582003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14582003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q18.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q18.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/744.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">744.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000160</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000160</a>]</span><br /> -
Downturned corners of mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866195&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866195</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002714" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002714</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002714" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002714</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5c723b1624611f01765e9a80de6b5b31" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Mouth,Downturned_Corners_of-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5c723b1624611f01765e9a80de6b5b31&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> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hyperventilation and cyanosis (in infancy) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5936260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5936260</a>]</span><br />
</span>
</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> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow chest <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249671009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249671009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000774" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000774</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000774" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000774</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Downward sloping ribs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850188&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850188</a>]</span><br /> -
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>
<span class="h5 mim-font">
<em> Breasts </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Gynecomastia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4754008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4754008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N62</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000771</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000771</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cryptorchidism, bilateral (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/268228006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">268228006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431663&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431663</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008689</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008689</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Joint contractures (fingers, hips, knees) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850193&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850193</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7890003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7890003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/718.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.4</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/718.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.40</a>]</span><br /> -
Generalized osteoporosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551680&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551680</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040160</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040160</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Skull </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Brachycephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13649004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13649004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221356&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221356</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000248" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000248</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000248" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000248</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9ccc4d161e106e4d5543286323f007ce" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Brachycephaly-Large-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9ccc4d161e106e4d5543286323f007ce&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 /> -
Basilar impression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86587003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86587003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551802</a>, <a href="https://bioportal.bioontology.org/search?q=C0032209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0032209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002691" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002691</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0005758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005758</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005758</a>]</span><br /> -
Maxillary hypoplasia <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.03</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240310&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240310</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000327</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000327</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br /> -
Endplate irregularities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842153&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842153</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003301" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003301</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003301" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003301</a>]</span><br /> -
Posterior scalloping of vertebral bodies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850196&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850196</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005121" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005121</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005121" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005121</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow iliac wings <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836688&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836688</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002868" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002868</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002868" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002868</a>]</span><br /> -
Flexion contractures (hips) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/202283002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">202283002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0409354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0409354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003273" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003273</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.20</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</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">
- Genu valgum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299330008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299330008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52012001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52012001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.06" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.06</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158484</a>, <a href="https://bioportal.bioontology.org/search?q=C0576093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002857" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002857</a>]</span><br /> -
Flexion contractures (knees) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/202289003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">202289003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0409355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0409355</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006380</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.20</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span><br /> -
Cystic bone lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850197&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850197</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short terminal phalanges <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850198&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850198</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 /> -
Metatarsus varus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23568008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23568008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.22</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265647&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265647</a>, <a href="https://bioportal.bioontology.org/search?q=C4082169&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4082169</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001840" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001840</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001840" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001840</a>]</span><br /> -
Flexed toes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278629</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Nails </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Dystrophic fingernails and toenails <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278630&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278630</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Absent facial, axillary, body hair <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850199&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850199</a>]</span><br /> -
Sparse scalp hair <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857042&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857042</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002209</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002209</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0794250547c51da4a5a0f6e06193a00b" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Scalp_Hair,Sparse-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0794250547c51da4a5a0f6e06193a00b&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> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Distal muscle wasting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848736&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848736</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</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">
- Impaired intellectual development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4747273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4747273</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Fainting spells <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/272030005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">272030005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271594007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271594007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/309585006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">309585006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R55" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R55</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0039070&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039070</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001279" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001279</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0007185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007185</a>]</span><br /> -
Neurodegeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027746&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027746</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span><br /> -
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 /> -
Hypoplastic corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204043002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204043002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0344482&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344482</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002079" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002079</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002079" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002079</a>]</span><br /> -
Intracerebral calcifications (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17944005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17944005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270685</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002514" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002514</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0430048" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0430048</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Behavioral Psychiatric Manifestations </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Autism (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35919005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35919005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/408857007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">408857007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43614003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43614003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F84.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F84.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/299" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/299.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/299.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">299.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0524528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0524528</a>, <a href="https://bioportal.bioontology.org/search?q=C0004352&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004352</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000717" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000717</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000717" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000717</a>]</span><br /> -
Self-injurious behavior (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248062006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248062006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R45.88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R45.88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085271&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085271</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100716</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100716</a>]</span><br /> -
Aggression (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/61372001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">61372001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001807&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001807</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006919</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000718</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000718</a>]</span><br /> -
Tics or anxieties (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012179&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012179</a>]</span><br /> -
Repetitive compulsive movements (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012180&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012180</a>]</span><br /> -
Phobias (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386808001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386808001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386810004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386810004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F40.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F40.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/300.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">300.20</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/300.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">300.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:5200232" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:5200232</a>]</span><br /> -
Restlessness (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/162221009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">162221009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/47295007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">47295007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/24199005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">24199005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887612&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887612</a>, <a href="https://bioportal.bioontology.org/search?q=C0085631&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085631</a>, <a href="https://bioportal.bioontology.org/search?q=C3887611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887611</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000713" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000713</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000711" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000711</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000711" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000711</a>]</span><br /> -
Frequent confabulation (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315753&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315753</a>]</span><br />
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<strong> ENDOCRINE FEATURES </strong>
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- Abnormal glucose tolerance test <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274858002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274858002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0159069&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0159069</a>]</span><br /> -
Insulin-resistant diabetes mellitus in adulthood <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012176&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012176</a>]</span><br /> -
Congenital hypothyroidism (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/217710005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">217710005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/190268003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">190268003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E03.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E03.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/243" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">243</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010308&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010308</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000851" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000851</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000851" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000851</a>]</span><br /> -
Hypergonadotropic hypogonadism (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/370999003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">370999003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0948896&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0948896</a>, <a href="https://bioportal.bioontology.org/search?q=C1416843&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1416843</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000815" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000815</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000815" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000815</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Some features are variably present<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the zinc finger and BTB-domain containing 20 gene (ZBTB20, <a href="/entry/606025#0001">606025.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that Primrose syndrome (PRIMS) is caused by heterozygous mutation in the ZBTB20 gene (<a href="/entry/606025">606025</a>) on chromosome 3q13.</p>
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<div class="mim-changed mim-change"><p>Primrose syndrome (PRIMS) consists of recognizable facial features, macrocephaly, impaired intellectual development, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by <a href="#2" class="mim-tip-reference" title="Carvalho, D. R., Speck-Martins, C. E. &lt;strong&gt;Additional features of unique Primrose syndrome phenotype.&lt;/strong&gt; Am. J. Med. Genet. 155A: 1379-1383, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21567911/&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;21567911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33955&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="21567911">Carvalho and Speck-Martins, 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21567911" 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></div>
<p>Patients with a deletion syndrome involving 3q13.31 (<a href="/entry/615433">615433</a>) exhibit features overlapping those of Primrose syndrome.</p>
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<strong>Clinical Features</strong>
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<p><a href="#13" class="mim-tip-reference" title="Primrose, D. A. &lt;strong&gt;A slowly progressive degenerative condition characterized by mental deficiency, wasting of limb musculature and bone abnormalities, including ossification of the pinnae.&lt;/strong&gt; J. Ment. Defic. Res. 26: 101-106, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6809950/&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;6809950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1365-2788.1982.tb00133.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6809950">Primrose (1982)</a> described the single case of a 33-year-old male with mental retardation who had been institutionalized from the age of 12 years. The parents were not related. He showed progressive wasting of the distal muscles of the legs and later of the small muscles of the hands. The cartilage of each pinna was extensively ossified, and photographs showing a fracture were presented. Cystic changes were observed in the head of the humerus and of the femurs, with deformity or destruction of the articular surfaces. Bilateral circumscribed, whitish, paracentral posterior polar cataracts were also described. He had had recurrent attacks of bilateral otitis media and was somewhat deaf. There was a 'hard mass filling in the cavity of the hard palate' which was not radioopaque. The same condition may have been described by <a href="#4" class="mim-tip-reference" title="Collacott, R. A., O&#x27;Malley, B. P., Young, I. D. &lt;strong&gt;The syndrome of mental handicap, cataracts, muscle wasting and skeletal abnormalities: report of a second case.&lt;/strong&gt; J. Ment. Defic. Res. 30: 301-308, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3783663/&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;3783663&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1365-2788.1986.tb01324.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3783663">Collacott et al. (1986)</a>. Their patient had large, calcified pinnae, and the buccal cavity was reduced by a large, soft-tissue mass extending over the inferior surface of the hard palate. Both lower limbs were wasted distally, and the hands were small and wasted. He had had recurrent attacks of otitis media and was profoundly deaf; he had dense bilateral cataracts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6809950+3783663" 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="Lindor, N. M., Hoffman, A. D., Primrose, D. A. &lt;strong&gt;A neuropsychiatric disorder associated with dense calcification of the external ears and distal muscle wasting: &#x27;Primrose syndrome&#x27;.&lt;/strong&gt; Clin. Dysmorph. 5: 27-34, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8867656/&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;8867656&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00019605-199601000-00004&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="8867656">Lindor et al. (1996)</a> described a third affected male who also had schizophrenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8867656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Mathijssen, I. B., van Hasselt-van der Velde, J., Hennekam, R. C. M. &lt;strong&gt;Testicular cancer in a patient with Primrose syndrome.&lt;/strong&gt; Europ. J. Med. Genet. 49: 127-133, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16530709/&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;16530709&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2005.06.001&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="16530709">Mathijssen et al. (2006)</a> described a man with mental retardation who had joint contractures, sparse body hair, hearing loss, dysmorphic facial features, and, as cardinal features suggesting Primrose syndrome, large calcified pinnae and a huge torus palatinus. In addition, he developed a germ cell tumor of his right testicle at age 27 years. It was uncertain whether an increased risk of malignancy forms part of this syndrome or is only a consequence of cryptorchidism in the patient reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16530709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J. &lt;strong&gt;Motor tics, stereotypies, and self-flagellation in Primrose syndrome.&lt;/strong&gt; Neurology 75: 284-286, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20644156/&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;20644156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181e8e754&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="20644156">Dalal et al. (2010)</a> reported a 43-year-old woman with all the clinical elements of Primrose syndrome who remained undiagnosed for over 4 decades. She was born with congenital heart disease, hip dysplasia, and agenesis of the corpus callosum. In childhood, she was noted to have hearing impairment, cataracts, neoplasm of the bone in the palate, ossification of cartilage, cystic bone changes, diabetes mellitus, and hypothyroidism. She walked at age 6 years and was severely mentally retarded. She slowly lost the ability to walk, had distal muscle wasting, and needed a wheelchair by age 40. She had dysmorphic facial features, including micrognathia, anteverted nares, prominent ears and nasal root, ptosis, and microphthalmia. She also had spastic paraparesis, areflexia, motor tics, hand stereotypies, and self-flagellating behaviors. Brain MRI showed partial calcification of the basal ganglia, and laboratory studies showed increase serum calcitonin. Microarray analysis detected a small 225.5-kb deletion on chromosome 11p between <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs12275693;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs12275693</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1442927;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1442927</a> encompassing the BBOX1 gene (<a href="/entry/603312">603312</a>). <a href="#6" class="mim-tip-reference" title="Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J. &lt;strong&gt;Motor tics, stereotypies, and self-flagellation in Primrose syndrome.&lt;/strong&gt; Neurology 75: 284-286, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20644156/&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;20644156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181e8e754&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="20644156">Dalal et al. (2010)</a> postulated an abnormality in calcium homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20644156" 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="Carvalho, D. R., Speck-Martins, C. E. &lt;strong&gt;Additional features of unique Primrose syndrome phenotype.&lt;/strong&gt; Am. J. Med. Genet. 155A: 1379-1383, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21567911/&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;21567911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33955&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="21567911">Carvalho and Speck-Martins (2011)</a> described a 23-year-old Brazilian man, born of nonconsanguineous parents, who had mental retardation and developmental delay, macrocephaly, wide forehead, broad face, deeply set eyes, downslanting palpebral fissures with mild ptosis, large ears, high nasal bridge, large jaw, and apparently small mouth. The ears were unusually firm and immobile. He had thoracic kyphosis but no scoliosis, and genu valgum with distal muscle wasting of the lower extremities was apparent. Ankles and elbows had mild reduction of mobility. He also displayed sparse body hair and thin, dystrophic fingernails and toenails. There was scaly, thickened skin over extensor joint surfaces, and a great number of pigmented nevi as well as some striae were present. Examination at 23 years of age showed poor coordination and mild bradykinesia, but follow-up over 2 decades did not reveal progressive neurologic involvement. Hearing loss was not clinically noticeable, but audiometric evaluation detected a bilateral moderate mixed hearing loss. Skeletal x-rays showed calcification of the ear cartilages, thoracic kyphosis, and sloping ribs; osteopenia was not noted. CT of the head revealed uniform and extensive calcification of both pinnae and part of the external ear canals, with no brain calcification. Echocardiography showed signs of concentric left ventricular remodeling. <a href="#2" class="mim-tip-reference" title="Carvalho, D. R., Speck-Martins, C. E. &lt;strong&gt;Additional features of unique Primrose syndrome phenotype.&lt;/strong&gt; Am. J. Med. Genet. 155A: 1379-1383, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21567911/&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;21567911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33955&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="21567911">Carvalho and Speck-Martins (2011)</a> reviewed the key features of the 7 reported patients with Primrose syndrome, noting that all cases had been sporadic, with no familial occurrence or consanguinity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21567911" 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="#12" class="mim-tip-reference" title="Posmyk, R., Lesniewicz, R., Chorazy, M., Wolczynski, S. &lt;strong&gt;New case of Primrose syndrome with mild intellectual disability.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2838-2840, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21910247/&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;21910247&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34257&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="21910247">Posmyk et al. (2011)</a> reported a 27-year-old man with Primrose syndrome who had only mild mental retardation. He also exhibited hypergonadotropic hypogonadism and low bone density due to progressive osteoporosis. <a href="#12" class="mim-tip-reference" title="Posmyk, R., Lesniewicz, R., Chorazy, M., Wolczynski, S. &lt;strong&gt;New case of Primrose syndrome with mild intellectual disability.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2838-2840, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21910247/&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;21910247&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34257&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="21910247">Posmyk et al. (2011)</a> stated that their findings confirmed that Primrose syndrome is a progressive neurodegenerative disorder with late-onset neurologic signs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21910247" 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="#5" class="mim-tip-reference" title="Cordeddu, V., Redeker, B., Stellacci, E., Jongejan, A., Fragale, A., Bradley, T. E. J., Anselmi, M., Ciolfi, A., Cecchetti, S., Muto, V., Bernardini, L., Azage, M., and 15 others. &lt;strong&gt;Mutations in ZBTB20 cause Primrose syndrome.&lt;/strong&gt; Nature Genet. 46: 815-817, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25017102/&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;25017102&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.3035&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="25017102">Cordeddu et al. (2014)</a> studied 8 individuals with Primrose syndrome, 5 of whom had previously been described in detail (<a href="#1" class="mim-tip-reference" title="Battisti, C., Dotti, M. T., Cerase, A., Rufa, A., Sicurelli, F., Scarpini, C., Federico, A. &lt;strong&gt;The Primrose syndrome with progressive neurological involvement and cerebral calcification. (Letter)&lt;/strong&gt; J. Neurol. 249: 1466-1468, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12532939/&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;12532939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-002-0850-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12532939">Battisti et al., 2002</a>; <a href="#10" class="mim-tip-reference" title="Mathijssen, I. B., van Hasselt-van der Velde, J., Hennekam, R. C. M. &lt;strong&gt;Testicular cancer in a patient with Primrose syndrome.&lt;/strong&gt; Europ. J. Med. Genet. 49: 127-133, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16530709/&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;16530709&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2005.06.001&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="16530709">Mathijssen et al., 2006</a>; <a href="#6" class="mim-tip-reference" title="Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J. &lt;strong&gt;Motor tics, stereotypies, and self-flagellation in Primrose syndrome.&lt;/strong&gt; Neurology 75: 284-286, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20644156/&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;20644156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181e8e754&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="20644156">Dalal et al., 2010</a>; <a href="#2" class="mim-tip-reference" title="Carvalho, D. R., Speck-Martins, C. E. &lt;strong&gt;Additional features of unique Primrose syndrome phenotype.&lt;/strong&gt; Am. J. Med. Genet. 155A: 1379-1383, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21567911/&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;21567911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33955&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="21567911">Carvalho and Speck-Martins, 2011</a>; <a href="#12" class="mim-tip-reference" title="Posmyk, R., Lesniewicz, R., Chorazy, M., Wolczynski, S. &lt;strong&gt;New case of Primrose syndrome with mild intellectual disability.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2838-2840, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21910247/&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;21910247&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34257&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="21910247">Posmyk et al., 2011</a>), and all of whom had mutations in the ZBTB20 gene. Mutation-positive patients exhibited a consistent phenotype characterized by increased growth, variable intellectual disability, autistic traits and other behavioral problems, hypotonia, and distinctive facial features overlapping with the phenotype of the 3q13.31 deletion syndrome (<a href="/entry/615433">615433</a>). However, the phenotype in the Primrose syndrome patients was more severe, including disturbances of glucose metabolism with insulin-resistant diabetes occurring in adulthood, distal muscle wasting resulting in contractures in adulthood, and hearing loss and ectopic calcification of the ears and brain during puberty or early adulthood. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20644156+21910247+12532939+25017102+21567911+16530709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Battisti, C., Dotti, M. T., Cerase, A., Rufa, A., Sicurelli, F., Scarpini, C., Federico, A. &lt;strong&gt;The Primrose syndrome with progressive neurological involvement and cerebral calcification. (Letter)&lt;/strong&gt; J. Neurol. 249: 1466-1468, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12532939/&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;12532939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-002-0850-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12532939">Battisti et al. (2002)</a> reported a 49-year-old woman who exhibited the classic features of Primrose syndrome, associated with late-onset progressive gait ataxia, pyramidal signs, and cerebral calcification. Neurologic examination revealed severe mental retardation, frequent confabulation, severely impaired spastic-ataxic gait, positive Romberg sign, slight hypertonia, mild muscular atrophy of the limbs, upper limb areflexia, brisk tendon reflexes in the legs, bilateral ankle clonus, and Babinski sign. Brain CT showed areas of dense calcification in both heads of the caudate nuclei, with less dense calcification in both globi pallidi and in the anterior limb of the left internal capsule; dense calcification of both external ears was also evident. Muscle biopsy was suggestive of neurogenic atrophy. The authors noted that this was the first reported case of a female patient with Primrose syndrome, and suggested that the diagnosis should be considered in patients with syndromic mental retardation plus progressive neurologic involvement, including cerebral calcification, ataxia, and peripheral neuropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12532939" 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="Mattioli, F., Piton, A., Gerard, B., Superti-Furga, A., Mandel, J.-L., Unger, S. &lt;strong&gt;Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.&lt;/strong&gt; Am. J. Med. Genet. 170A: 1626-1629, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27061120/&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;27061120&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37645&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="27061120">Mattioli et al. (2016)</a> studied a 4-year-old boy, ascertained from a cohort of patients with developmental delay, in whom targeted sequencing of candidate genes revealed mutations in the ZBTB20 gene. Reverse phenotyping showed that the patient presented the classic features of Primrose syndrome, including dysmorphic facies, macrocephaly, hearing loss, hypotonia, and hypoplasia of the corpus callosum. His ears were large, but were supple to palpation with no evidence of calcification; the authors noted that calcified pinnae had only been observed in adult cases. In addition, the proband had congenital hypothyroidism, and thyroid scan showed a large volume thyroid gland with homogeneous uptake suggesting a problem in thyroid hormone synthesis. <a href="#11" class="mim-tip-reference" title="Mattioli, F., Piton, A., Gerard, B., Superti-Furga, A., Mandel, J.-L., Unger, S. &lt;strong&gt;Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.&lt;/strong&gt; Am. J. Med. Genet. 170A: 1626-1629, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27061120/&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;27061120&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37645&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="27061120">Mattioli et al. (2016)</a> noted that one other patient with Primrose syndrome had been reported to have hypothyroidism (<a href="#6" class="mim-tip-reference" title="Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J. &lt;strong&gt;Motor tics, stereotypies, and self-flagellation in Primrose syndrome.&lt;/strong&gt; Neurology 75: 284-286, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20644156/&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;20644156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181e8e754&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="20644156">Dalal et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27061120+20644156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Stellacci, E., Steindl, K., Joset, P., Mercurio, L., Anselmi, M., Cecchetti, S., Gogoll, L., Zweier, M., Hackenberg, A., Bocchinfuso, G., Stella, L., Tartaglia, M., Rauch, A. &lt;strong&gt;Clinical and functional characterization of two novel ZBTB20 mutations causing Primrose syndrome.&lt;/strong&gt; Hum. Mutat. 39: 959-964, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29737001/&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;29737001&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.23546&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="29737001">Stellacci et al. (2018)</a> reported 2 patients with Primrose syndrome. Patient 1 was an 8.5-year-old boy with mild developmental delay. Head circumference was normal at birth, but by age 19 months, he had macrocephaly and a brain MRI with prominent subarachnoid spaces, hypoplastic corpus callosum, and a small pituitary pars intermedia cyst. At the age of 7.5 years, his height was at the 90th centile, weight was at the 97th centile, and head circumference was greater than the 97th centile with a prominent occiput. He had convergent strabismus. Facial features included a narrow forehead, underdeveloped supraorbital ridges, medial flaring and laterally sparse eyebrows, narrow palpebral fissures, malar flattening, wide and depressed nasal bridge, broad nasal tip, short and deep philtrum, thick and everted upper and lower lip vermilion, hypotonic open mouth appearance, and overfolded helices and posteriorly angulated ears with large forward-facing lobes. He had upper incisor diastema and delayed teeth eruption. Ankle contractures were noted at the age of 9 years. Patient 2 was a 3-year-old girl with global developmental delay. At birth, head circumference was at the 90th centile. Bilateral hearing loss was noted at birth. Brain MRI at 10 months of age showed partial agenesis of the corpus callosum. At 14 months of age, she had macrocephaly, developmental delay, and muscular hypotonia. Growth parameters were weight at the 50th to 75th centile, length at the 75th to 90th centile, and head circumference greater than the 97th centile. She had a broad face and forehead, high anterior hairline, long ears with increased posterior angulation, short palpebral fissures with deeply set eyes, convergent strabismus, underdeveloped supraorbital ridges, medial flaring of eyebrows with lateral thinning, malar flattening, full cheeks, prominent nasal bridge with wide nasal base, short columella, mildly thickened alae nasi, deep philtrum, thin upper lip vermilion and mildly everted lower lip vermilion, and diastema of the upper central incisors. She had short hands, broadened thumbs, short terminal phalanges of the 5th fingers bilaterally, deep palmar creases, and bilateral sandal gaps. She had hypertrichosis on her back. She also had muscular hypotonia of the extremities and trunk. Neither patient had disturbed glucose metabolism, cataracts, or ectopic calcification of the ears and brain, suggesting that these occur later in childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29737001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Grimsdottir, S., Hove, H. B., Kreiborg, S., Ek, J., Johansen, A., Darvann, T. A., Hermann, N. V. &lt;strong&gt;Novel de novo mutation in ZBTB20 in primrose syndrome in boy with short stature.&lt;/strong&gt; Clin. Dysmorph. 28: 41-45, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30256248/&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;30256248&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/MCD.0000000000000244&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="30256248">Grimsdottir et al. (2019)</a> reported a 14-year old boy with many features of Primrose syndrome, including macrocephaly, intellectual disability, agenesis of the corpus callosum, hearing impairment, and characteristic facial dysmorphology, and a mutation in the ZBTB20 gene. Facial features included downslanting palpebral fissures, low-set ears, flat hypoplastic midface with maxillary retrognathia, relative mandibular prognathism, and a narrow and tapered lower face and chin. The patient also had short stature and did not respond sufficiently to growth hormone therapy. Craniofacial and dental findings not previously reported in Primrose syndrome included large paranasal sinuses, narrow cranial base, decreased cranial base angle, maxillary hypoplasia, a supernumerary tooth, and retention of 2 mandibular premolars. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30256248" 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="#7" class="mim-tip-reference" title="Ferreira, L. D., Borges-Medeiros, R. L., Thies, J., Schnur, R. E., Lam, C., de Oliveira, J. R. M. &lt;strong&gt;Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2228-2232, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31321892/&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;31321892&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61297&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="31321892">Ferreira et al. (2019)</a> reported 2 unrelated patients, a 2-year-old boy and a 27-year-old man, with Primrose syndrome. Both patients had hearing impairment, cognitive delays, skeletal abnormalities, and dysmorphic features including frontal bossing, deep-set eyes, large ears, and prominent chin. Both patients also had fainting spells in infancy consisting of hyperventilation and cyanosis followed by loss of consciousness; these spells mainly occurred when the patients were upset. The younger patient had macrocephaly, and brain imaging showed hypoplasia of the corpus callosum. The older patient had ectopic calcifications in outer ears and brain, torus palatinus, sparse body hair, short first metatarsals, and distal muscle wasting. Neuroimaging studies showed diminished gyri in the frontal lobe, persistent cavum septum pellucidum and cavum vergae cyst, and bilateral basal ganglia calcifications. The older patient also had diminishing growth, with height at 99th centile in infancy progressing to 0.2nd centile at 6 years of age. The authors proposed that Primrose syndrome is a progressive condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31321892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Cleaver, R., Berg, J., Craft, E., Foster, A., Gibbons, R. J., Hobson, E., Lachlan, K., Naik, S., Sampson, J. R., Sharif, S., Smithson, S., Deciphering Developmental Disorders Study, Parker, M. J., Tatton-Brown, K. &lt;strong&gt;Refining the Primrose syndrome phenotype: a study of five patients with ZBTB20 de novo variants and a review of the literature.&lt;/strong&gt; Am. J. Med. Genet. 179A: 344-349, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30637921/&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;30637921&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61024&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="30637921">Cleaver et al. (2019)</a> reported 5 unrelated patients, aged 2 to 13 years, with Primrose syndrome and reviewed 14 other patients with de novo ZBTB20 missense variants to further refine the phenotype. Major clinical features (reported in over 90%) included intellectual disability, most often in moderate range; abnormal findings on MRI, most often abnormalities of the corpus callosum; and a characteristic facial appearance with prominent forehead, deep-set eyes, downslanting and narrow palpebral fissures, small mouth, thin upper lip, pointed chin, and large fleshy ears. Other findings included hearing loss (15/18), hypotonia (14/18), cryptorchidism (6/8), macrocephaly (13/18), behavioral issues (10/18) and abnormal nails (8/14). Findings in more than 80% of adult patients included distal muscle wasting, abnormalities of glucose metabolism, contractures, and ectopic calcification of pinnae. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30637921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The heterozygous mutations in the ZBTB20 gene that were identified in patients with Primrose syndrome by <a href="#5" class="mim-tip-reference" title="Cordeddu, V., Redeker, B., Stellacci, E., Jongejan, A., Fragale, A., Bradley, T. E. J., Anselmi, M., Ciolfi, A., Cecchetti, S., Muto, V., Bernardini, L., Azage, M., and 15 others. &lt;strong&gt;Mutations in ZBTB20 cause Primrose syndrome.&lt;/strong&gt; Nature Genet. 46: 815-817, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25017102/&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;25017102&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.3035&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="25017102">Cordeddu et al. (2014)</a> occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25017102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 4 unrelated patients with Primrose syndrome, including the patients reported by <a href="#10" class="mim-tip-reference" title="Mathijssen, I. B., van Hasselt-van der Velde, J., Hennekam, R. C. M. &lt;strong&gt;Testicular cancer in a patient with Primrose syndrome.&lt;/strong&gt; Europ. J. Med. Genet. 49: 127-133, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16530709/&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;16530709&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2005.06.001&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="16530709">Mathijssen et al. (2006)</a>, <a href="#6" class="mim-tip-reference" title="Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J. &lt;strong&gt;Motor tics, stereotypies, and self-flagellation in Primrose syndrome.&lt;/strong&gt; Neurology 75: 284-286, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20644156/&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;20644156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181e8e754&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="20644156">Dalal et al. (2010)</a>, and <a href="#2" class="mim-tip-reference" title="Carvalho, D. R., Speck-Martins, C. E. &lt;strong&gt;Additional features of unique Primrose syndrome phenotype.&lt;/strong&gt; Am. J. Med. Genet. 155A: 1379-1383, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21567911/&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;21567911&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33955&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="21567911">Carvalho and Speck-Martins (2011)</a>, <a href="#5" class="mim-tip-reference" title="Cordeddu, V., Redeker, B., Stellacci, E., Jongejan, A., Fragale, A., Bradley, T. E. J., Anselmi, M., Ciolfi, A., Cecchetti, S., Muto, V., Bernardini, L., Azage, M., and 15 others. &lt;strong&gt;Mutations in ZBTB20 cause Primrose syndrome.&lt;/strong&gt; Nature Genet. 46: 815-817, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25017102/&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;25017102&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.3035&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="25017102">Cordeddu et al. (2014)</a> performed whole-exome sequencing and identified heterozygosity for de novo missense variants in the ZBTB20 gene (see, e.g., <a href="/entry/606025#0001">606025.0001</a> and <a href="/entry/606025#0002">606025.0002</a>); subsequent mutation analysis in 4 more affected individuals, including the patients reported by <a href="#1" class="mim-tip-reference" title="Battisti, C., Dotti, M. T., Cerase, A., Rufa, A., Sicurelli, F., Scarpini, C., Federico, A. &lt;strong&gt;The Primrose syndrome with progressive neurological involvement and cerebral calcification. (Letter)&lt;/strong&gt; J. Neurol. 249: 1466-1468, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12532939/&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;12532939&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00415-002-0850-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12532939">Battisti et al. (2002)</a> and <a href="#12" class="mim-tip-reference" title="Posmyk, R., Lesniewicz, R., Chorazy, M., Wolczynski, S. &lt;strong&gt;New case of Primrose syndrome with mild intellectual disability.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2838-2840, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21910247/&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;21910247&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34257&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="21910247">Posmyk et al. (2011)</a>, revealed a de novo heterozygous ZBTB20 missense mutation in each (see, e.g., <a href="/entry/606025#0003">606025.0003</a> and <a href="/entry/606025#0004">606025.0004</a>). Functional analysis showed strongly reduced DNA binding for all mutants compared to wildtype, and results were consistent with the mutations having a dominant-negative impact on the wildtype allele. The authors noted that the more severe phenotype seen in Primrose syndrome patients compared to that of patients with 3q13.31 deletion syndrome, who exhibit overlapping but milder features, was in line with a dominant-negative effect of the ZBTB20 mutations compared to the haploinsufficiency that likely underlies the 3q13.31 deletion syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20644156+21910247+12532939+25017102+21567911+16530709" 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>By targeted exome sequencing of 275 genes known to be or potentially associated with intellectual disability in a cohort of individuals with mild to severe developmental delay, who were negative for pathogenic CNV by array-CGH, <a href="#11" class="mim-tip-reference" title="Mattioli, F., Piton, A., Gerard, B., Superti-Furga, A., Mandel, J.-L., Unger, S. &lt;strong&gt;Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.&lt;/strong&gt; Am. J. Med. Genet. 170A: 1626-1629, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/27061120/&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;27061120&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.37645&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="27061120">Mattioli et al. (2016)</a> identified a 4-year-old boy with Primrose syndrome who was heterozygous for 2 de novo missense mutations on the same allele of the ZBTB20 gene (<a href="/entry/606025#0005">606025.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27061120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 14-year-old boy with Primrose syndrome, <a href="#8" class="mim-tip-reference" title="Grimsdottir, S., Hove, H. B., Kreiborg, S., Ek, J., Johansen, A., Darvann, T. A., Hermann, N. V. &lt;strong&gt;Novel de novo mutation in ZBTB20 in primrose syndrome in boy with short stature.&lt;/strong&gt; Clin. Dysmorph. 28: 41-45, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30256248/&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;30256248&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/MCD.0000000000000244&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="30256248">Grimsdottir et al. (2019)</a> identified heterozygosity for a de novo missense mutation in the ZBTB20 gene (H600Q; <a href="/entry/606025#0006">606025.0006</a>). The mutation was found by exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30256248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients with Primrose syndrome, <a href="#14" class="mim-tip-reference" title="Stellacci, E., Steindl, K., Joset, P., Mercurio, L., Anselmi, M., Cecchetti, S., Gogoll, L., Zweier, M., Hackenberg, A., Bocchinfuso, G., Stella, L., Tartaglia, M., Rauch, A. &lt;strong&gt;Clinical and functional characterization of two novel ZBTB20 mutations causing Primrose syndrome.&lt;/strong&gt; Hum. Mutat. 39: 959-964, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29737001/&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;29737001&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.23546&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="29737001">Stellacci et al. (2018)</a> identified de novo heterozygous mutations in the ZBTB20 gene: the first reported frameshift mutation (c.1024delC; <a href="/entry/606025#0007">606025.0007</a>) and a missense mutation (T644I; <a href="/entry/606025#0008">606025.0008</a>) in the third zinc finger motif of the protein. The authors noted that previously reported mutations occurred in the first and second zinc finger motifs. Functional data showed that both mutations result in stable but dysfunctional proteins characterized by impaired binding to DNA, consistent with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29737001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 2-year-old boy and an unrelated 27-year-old man with Primrose syndrome, <a href="#7" class="mim-tip-reference" title="Ferreira, L. D., Borges-Medeiros, R. L., Thies, J., Schnur, R. E., Lam, C., de Oliveira, J. R. M. &lt;strong&gt;Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2228-2232, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31321892/&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;31321892&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61297&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="31321892">Ferreira et al. (2019)</a> identified heterozygous mutations in the ZBTB20 gene. In the 2-year-old boy, trio exome sequencing identified a novel de novo cys608-to-arg substitution (C608R; <a href="/entry/606025#0009">606025.0009</a>). In the 27-year-old man, Sanger sequencing identified a heterozygous met625-to-val (M625V) substitution (M625V; <a href="/entry/606025#0010">606025.0010</a>). The M625V variant was not found in the patient's mother or healthy sibs; paternal DNA was unavailable. The variants in both patients occurred in the last coding exon of the ZBTB20 gene and in the second zinc finger domain of the ZBTB20 protein. Neither variant was seen in large population databases; the M625V variant had been previously deposited in ClinVar and dbSNP databases as a likely pathogenic variant, although supporting clinical data were not publicly available. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31321892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 unrelated patients with Primrose syndrome, <a href="#3" class="mim-tip-reference" title="Cleaver, R., Berg, J., Craft, E., Foster, A., Gibbons, R. J., Hobson, E., Lachlan, K., Naik, S., Sampson, J. R., Sharif, S., Smithson, S., Deciphering Developmental Disorders Study, Parker, M. J., Tatton-Brown, K. &lt;strong&gt;Refining the Primrose syndrome phenotype: a study of five patients with ZBTB20 de novo variants and a review of the literature.&lt;/strong&gt; Am. J. Med. Genet. 179A: 344-349, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30637921/&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;30637921&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61024&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="30637921">Cleaver et al. (2019)</a> used trio exome sequencing to identify novel de novo heterozygous pathogenic missense variants in the ZBTB20 gene. Consistent with previous reports, all 5 variants occurred within the C2H2 zinc finger domains. The variants in 2 patients (patients 4 and 5) were in the third zinc finger domain (e.g., <a href="/entry/606025#0011">606025.0011</a>), where only 2 pathogenic variants had previously been seen. One patient (patient 4) was mosaic for the variant in blood and saliva. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30637921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Battisti2002" class="mim-anchor"></a>
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<p class="mim-text-font">
Battisti, C., Dotti, M. T., Cerase, A., Rufa, A., Sicurelli, F., Scarpini, C., Federico, A.
<strong>The Primrose syndrome with progressive neurological involvement and cerebral calcification. (Letter)</strong>
J. Neurol. 249: 1466-1468, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12532939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12532939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12532939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s00415-002-0850-x" target="_blank">Full Text</a>]
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<a id="Carvalho2011" class="mim-anchor"></a>
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Carvalho, D. R., Speck-Martins, C. E.
<strong>Additional features of unique Primrose syndrome phenotype.</strong>
Am. J. Med. Genet. 155A: 1379-1383, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21567911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21567911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21567911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.33955" target="_blank">Full Text</a>]
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<a id="Cleaver2019" class="mim-anchor"></a>
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Cleaver, R., Berg, J., Craft, E., Foster, A., Gibbons, R. J., Hobson, E., Lachlan, K., Naik, S., Sampson, J. R., Sharif, S., Smithson, S., Deciphering Developmental Disorders Study, Parker, M. J., Tatton-Brown, K.
<strong>Refining the Primrose syndrome phenotype: a study of five patients with ZBTB20 de novo variants and a review of the literature.</strong>
Am. J. Med. Genet. 179A: 344-349, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30637921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30637921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30637921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.61024" target="_blank">Full Text</a>]
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<a id="Collacott1986" class="mim-anchor"></a>
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Collacott, R. A., O'Malley, B. P., Young, I. D.
<strong>The syndrome of mental handicap, cataracts, muscle wasting and skeletal abnormalities: report of a second case.</strong>
J. Ment. Defic. Res. 30: 301-308, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3783663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3783663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3783663" 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.1365-2788.1986.tb01324.x" target="_blank">Full Text</a>]
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<a id="Cordeddu2014" class="mim-anchor"></a>
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Cordeddu, V., Redeker, B., Stellacci, E., Jongejan, A., Fragale, A., Bradley, T. E. J., Anselmi, M., Ciolfi, A., Cecchetti, S., Muto, V., Bernardini, L., Azage, M., and 15 others.
<strong>Mutations in ZBTB20 cause Primrose syndrome.</strong>
Nature Genet. 46: 815-817, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25017102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25017102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25017102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng.3035" target="_blank">Full Text</a>]
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<a id="Dalal2010" class="mim-anchor"></a>
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Dalal, P., Leslie, N. D., Lindor, N. M., Gilbert, D. L., Espay, A. J.
<strong>Motor tics, stereotypies, and self-flagellation in Primrose syndrome.</strong>
Neurology 75: 284-286, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20644156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20644156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20644156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0b013e3181e8e754" target="_blank">Full Text</a>]
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<a id="Ferreira2019" class="mim-anchor"></a>
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<p class="mim-text-font">
Ferreira, L. D., Borges-Medeiros, R. L., Thies, J., Schnur, R. E., Lam, C., de Oliveira, J. R. M.
<strong>Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants.</strong>
Am. J. Med. Genet. 179A: 2228-2232, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31321892/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31321892</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31321892" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.61297" target="_blank">Full Text</a>]
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<a id="Grimsdottir2019" class="mim-anchor"></a>
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<p class="mim-text-font">
Grimsdottir, S., Hove, H. B., Kreiborg, S., Ek, J., Johansen, A., Darvann, T. A., Hermann, N. V.
<strong>Novel de novo mutation in ZBTB20 in primrose syndrome in boy with short stature.</strong>
Clin. Dysmorph. 28: 41-45, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30256248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30256248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30256248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/MCD.0000000000000244" target="_blank">Full Text</a>]
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<a id="Lindor1996" class="mim-anchor"></a>
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Lindor, N. M., Hoffman, A. D., Primrose, D. A.
<strong>A neuropsychiatric disorder associated with dense calcification of the external ears and distal muscle wasting: 'Primrose syndrome'.</strong>
Clin. Dysmorph. 5: 27-34, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8867656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8867656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8867656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00019605-199601000-00004" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
<a id="Mathijssen2006" class="mim-anchor"></a>
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<p class="mim-text-font">
Mathijssen, I. B., van Hasselt-van der Velde, J., Hennekam, R. C. M.
<strong>Testicular cancer in a patient with Primrose syndrome.</strong>
Europ. J. Med. Genet. 49: 127-133, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16530709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16530709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16530709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ejmg.2005.06.001" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
<a id="Mattioli2016" class="mim-anchor"></a>
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Mattioli, F., Piton, A., Gerard, B., Superti-Furga, A., Mandel, J.-L., Unger, S.
<strong>Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.</strong>
Am. J. Med. Genet. 170A: 1626-1629, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27061120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27061120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27061120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.37645" target="_blank">Full Text</a>]
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Posmyk, R., Lesniewicz, R., Chorazy, M., Wolczynski, S.
<strong>New case of Primrose syndrome with mild intellectual disability.</strong>
Am. J. Med. Genet. 155A: 2838-2840, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21910247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21910247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21910247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.34257" target="_blank">Full Text</a>]
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Primrose, D. A.
<strong>A slowly progressive degenerative condition characterized by mental deficiency, wasting of limb musculature and bone abnormalities, including ossification of the pinnae.</strong>
J. Ment. Defic. Res. 26: 101-106, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6809950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6809950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6809950" 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.1365-2788.1982.tb00133.x" target="_blank">Full Text</a>]
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Stellacci, E., Steindl, K., Joset, P., Mercurio, L., Anselmi, M., Cecchetti, S., Gogoll, L., Zweier, M., Hackenberg, A., Bocchinfuso, G., Stella, L., Tartaglia, M., Rauch, A.
<strong>Clinical and functional characterization of two novel ZBTB20 mutations causing Primrose syndrome.</strong>
Hum. Mutat. 39: 959-964, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29737001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29737001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29737001" 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/humu.23546" target="_blank">Full Text</a>]
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Sonja A. Rasmussen - updated : 02/16/2024
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Sonja A. Rasmussen - updated : 01/31/2023<br>Sonja A. Rasmussen - updated : 02/15/2019<br>Marla J. F. O'Neill - updated : 08/08/2016<br>Marla J. F. O'Neill - updated : 8/27/2014<br>Marla J. F. O'Neill - updated : 10/19/2011<br>Cassandra L. Kniffin - updated : 6/20/2011<br>Victor A. McKusick - updated : 10/19/2006<br>Iosif W. Lurie - updated : 7/20/1996
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Victor A. McKusick : 12/22/1992
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carol : 02/18/2025
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alopez : 02/16/2024<br>carol : 01/31/2023<br>carol : 02/16/2019<br>carol : 02/15/2019<br>carol : 08/08/2016<br>carol : 07/15/2016<br>carol : 8/28/2014<br>mcolton : 8/27/2014<br>carol : 10/19/2011<br>terry : 10/19/2011<br>wwang : 6/28/2011<br>ckniffin : 6/20/2011<br>alopez : 10/23/2006<br>terry : 10/19/2006<br>carol : 7/20/1996<br>mimadm : 3/11/1994<br>carol : 12/22/1992
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<strong>#</strong> 259050
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PRIMROSE SYNDROME; PRIMS
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
OSSIFIED EAR CARTILAGES WITH MENTAL DEFICIENCY, MUSCLE WASTING, AND BONY CHANGES
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<strong>SNOMEDCT:</strong> 726709001; &nbsp;
<strong>ORPHA:</strong> 3042; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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3q13.31
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Primrose syndrome
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259050
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Autosomal dominant
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3
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ZBTB20
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606025
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Primrose syndrome (PRIMS) is caused by heterozygous mutation in the ZBTB20 gene (606025) on chromosome 3q13.</p>
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<strong>Description</strong>
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<p>Primrose syndrome (PRIMS) consists of recognizable facial features, macrocephaly, impaired intellectual development, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by Carvalho and Speck-Martins, 2011). </p><p>Patients with a deletion syndrome involving 3q13.31 (615433) exhibit features overlapping those of Primrose syndrome.</p>
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<strong>Clinical Features</strong>
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<p>Primrose (1982) described the single case of a 33-year-old male with mental retardation who had been institutionalized from the age of 12 years. The parents were not related. He showed progressive wasting of the distal muscles of the legs and later of the small muscles of the hands. The cartilage of each pinna was extensively ossified, and photographs showing a fracture were presented. Cystic changes were observed in the head of the humerus and of the femurs, with deformity or destruction of the articular surfaces. Bilateral circumscribed, whitish, paracentral posterior polar cataracts were also described. He had had recurrent attacks of bilateral otitis media and was somewhat deaf. There was a 'hard mass filling in the cavity of the hard palate' which was not radioopaque. The same condition may have been described by Collacott et al. (1986). Their patient had large, calcified pinnae, and the buccal cavity was reduced by a large, soft-tissue mass extending over the inferior surface of the hard palate. Both lower limbs were wasted distally, and the hands were small and wasted. He had had recurrent attacks of otitis media and was profoundly deaf; he had dense bilateral cataracts. </p><p>Lindor et al. (1996) described a third affected male who also had schizophrenia. </p><p>Mathijssen et al. (2006) described a man with mental retardation who had joint contractures, sparse body hair, hearing loss, dysmorphic facial features, and, as cardinal features suggesting Primrose syndrome, large calcified pinnae and a huge torus palatinus. In addition, he developed a germ cell tumor of his right testicle at age 27 years. It was uncertain whether an increased risk of malignancy forms part of this syndrome or is only a consequence of cryptorchidism in the patient reported. </p><p>Dalal et al. (2010) reported a 43-year-old woman with all the clinical elements of Primrose syndrome who remained undiagnosed for over 4 decades. She was born with congenital heart disease, hip dysplasia, and agenesis of the corpus callosum. In childhood, she was noted to have hearing impairment, cataracts, neoplasm of the bone in the palate, ossification of cartilage, cystic bone changes, diabetes mellitus, and hypothyroidism. She walked at age 6 years and was severely mentally retarded. She slowly lost the ability to walk, had distal muscle wasting, and needed a wheelchair by age 40. She had dysmorphic facial features, including micrognathia, anteverted nares, prominent ears and nasal root, ptosis, and microphthalmia. She also had spastic paraparesis, areflexia, motor tics, hand stereotypies, and self-flagellating behaviors. Brain MRI showed partial calcification of the basal ganglia, and laboratory studies showed increase serum calcitonin. Microarray analysis detected a small 225.5-kb deletion on chromosome 11p between rs12275693 and rs1442927 encompassing the BBOX1 gene (603312). Dalal et al. (2010) postulated an abnormality in calcium homeostasis. </p><p>Carvalho and Speck-Martins (2011) described a 23-year-old Brazilian man, born of nonconsanguineous parents, who had mental retardation and developmental delay, macrocephaly, wide forehead, broad face, deeply set eyes, downslanting palpebral fissures with mild ptosis, large ears, high nasal bridge, large jaw, and apparently small mouth. The ears were unusually firm and immobile. He had thoracic kyphosis but no scoliosis, and genu valgum with distal muscle wasting of the lower extremities was apparent. Ankles and elbows had mild reduction of mobility. He also displayed sparse body hair and thin, dystrophic fingernails and toenails. There was scaly, thickened skin over extensor joint surfaces, and a great number of pigmented nevi as well as some striae were present. Examination at 23 years of age showed poor coordination and mild bradykinesia, but follow-up over 2 decades did not reveal progressive neurologic involvement. Hearing loss was not clinically noticeable, but audiometric evaluation detected a bilateral moderate mixed hearing loss. Skeletal x-rays showed calcification of the ear cartilages, thoracic kyphosis, and sloping ribs; osteopenia was not noted. CT of the head revealed uniform and extensive calcification of both pinnae and part of the external ear canals, with no brain calcification. Echocardiography showed signs of concentric left ventricular remodeling. Carvalho and Speck-Martins (2011) reviewed the key features of the 7 reported patients with Primrose syndrome, noting that all cases had been sporadic, with no familial occurrence or consanguinity. </p><p>Posmyk et al. (2011) reported a 27-year-old man with Primrose syndrome who had only mild mental retardation. He also exhibited hypergonadotropic hypogonadism and low bone density due to progressive osteoporosis. Posmyk et al. (2011) stated that their findings confirmed that Primrose syndrome is a progressive neurodegenerative disorder with late-onset neurologic signs. </p><p>Cordeddu et al. (2014) studied 8 individuals with Primrose syndrome, 5 of whom had previously been described in detail (Battisti et al., 2002; Mathijssen et al., 2006; Dalal et al., 2010; Carvalho and Speck-Martins, 2011; Posmyk et al., 2011), and all of whom had mutations in the ZBTB20 gene. Mutation-positive patients exhibited a consistent phenotype characterized by increased growth, variable intellectual disability, autistic traits and other behavioral problems, hypotonia, and distinctive facial features overlapping with the phenotype of the 3q13.31 deletion syndrome (615433). However, the phenotype in the Primrose syndrome patients was more severe, including disturbances of glucose metabolism with insulin-resistant diabetes occurring in adulthood, distal muscle wasting resulting in contractures in adulthood, and hearing loss and ectopic calcification of the ears and brain during puberty or early adulthood. </p><p>Battisti et al. (2002) reported a 49-year-old woman who exhibited the classic features of Primrose syndrome, associated with late-onset progressive gait ataxia, pyramidal signs, and cerebral calcification. Neurologic examination revealed severe mental retardation, frequent confabulation, severely impaired spastic-ataxic gait, positive Romberg sign, slight hypertonia, mild muscular atrophy of the limbs, upper limb areflexia, brisk tendon reflexes in the legs, bilateral ankle clonus, and Babinski sign. Brain CT showed areas of dense calcification in both heads of the caudate nuclei, with less dense calcification in both globi pallidi and in the anterior limb of the left internal capsule; dense calcification of both external ears was also evident. Muscle biopsy was suggestive of neurogenic atrophy. The authors noted that this was the first reported case of a female patient with Primrose syndrome, and suggested that the diagnosis should be considered in patients with syndromic mental retardation plus progressive neurologic involvement, including cerebral calcification, ataxia, and peripheral neuropathy. </p><p>Mattioli et al. (2016) studied a 4-year-old boy, ascertained from a cohort of patients with developmental delay, in whom targeted sequencing of candidate genes revealed mutations in the ZBTB20 gene. Reverse phenotyping showed that the patient presented the classic features of Primrose syndrome, including dysmorphic facies, macrocephaly, hearing loss, hypotonia, and hypoplasia of the corpus callosum. His ears were large, but were supple to palpation with no evidence of calcification; the authors noted that calcified pinnae had only been observed in adult cases. In addition, the proband had congenital hypothyroidism, and thyroid scan showed a large volume thyroid gland with homogeneous uptake suggesting a problem in thyroid hormone synthesis. Mattioli et al. (2016) noted that one other patient with Primrose syndrome had been reported to have hypothyroidism (Dalal et al., 2010). </p><p>Stellacci et al. (2018) reported 2 patients with Primrose syndrome. Patient 1 was an 8.5-year-old boy with mild developmental delay. Head circumference was normal at birth, but by age 19 months, he had macrocephaly and a brain MRI with prominent subarachnoid spaces, hypoplastic corpus callosum, and a small pituitary pars intermedia cyst. At the age of 7.5 years, his height was at the 90th centile, weight was at the 97th centile, and head circumference was greater than the 97th centile with a prominent occiput. He had convergent strabismus. Facial features included a narrow forehead, underdeveloped supraorbital ridges, medial flaring and laterally sparse eyebrows, narrow palpebral fissures, malar flattening, wide and depressed nasal bridge, broad nasal tip, short and deep philtrum, thick and everted upper and lower lip vermilion, hypotonic open mouth appearance, and overfolded helices and posteriorly angulated ears with large forward-facing lobes. He had upper incisor diastema and delayed teeth eruption. Ankle contractures were noted at the age of 9 years. Patient 2 was a 3-year-old girl with global developmental delay. At birth, head circumference was at the 90th centile. Bilateral hearing loss was noted at birth. Brain MRI at 10 months of age showed partial agenesis of the corpus callosum. At 14 months of age, she had macrocephaly, developmental delay, and muscular hypotonia. Growth parameters were weight at the 50th to 75th centile, length at the 75th to 90th centile, and head circumference greater than the 97th centile. She had a broad face and forehead, high anterior hairline, long ears with increased posterior angulation, short palpebral fissures with deeply set eyes, convergent strabismus, underdeveloped supraorbital ridges, medial flaring of eyebrows with lateral thinning, malar flattening, full cheeks, prominent nasal bridge with wide nasal base, short columella, mildly thickened alae nasi, deep philtrum, thin upper lip vermilion and mildly everted lower lip vermilion, and diastema of the upper central incisors. She had short hands, broadened thumbs, short terminal phalanges of the 5th fingers bilaterally, deep palmar creases, and bilateral sandal gaps. She had hypertrichosis on her back. She also had muscular hypotonia of the extremities and trunk. Neither patient had disturbed glucose metabolism, cataracts, or ectopic calcification of the ears and brain, suggesting that these occur later in childhood. </p><p>Grimsdottir et al. (2019) reported a 14-year old boy with many features of Primrose syndrome, including macrocephaly, intellectual disability, agenesis of the corpus callosum, hearing impairment, and characteristic facial dysmorphology, and a mutation in the ZBTB20 gene. Facial features included downslanting palpebral fissures, low-set ears, flat hypoplastic midface with maxillary retrognathia, relative mandibular prognathism, and a narrow and tapered lower face and chin. The patient also had short stature and did not respond sufficiently to growth hormone therapy. Craniofacial and dental findings not previously reported in Primrose syndrome included large paranasal sinuses, narrow cranial base, decreased cranial base angle, maxillary hypoplasia, a supernumerary tooth, and retention of 2 mandibular premolars. </p><p>Ferreira et al. (2019) reported 2 unrelated patients, a 2-year-old boy and a 27-year-old man, with Primrose syndrome. Both patients had hearing impairment, cognitive delays, skeletal abnormalities, and dysmorphic features including frontal bossing, deep-set eyes, large ears, and prominent chin. Both patients also had fainting spells in infancy consisting of hyperventilation and cyanosis followed by loss of consciousness; these spells mainly occurred when the patients were upset. The younger patient had macrocephaly, and brain imaging showed hypoplasia of the corpus callosum. The older patient had ectopic calcifications in outer ears and brain, torus palatinus, sparse body hair, short first metatarsals, and distal muscle wasting. Neuroimaging studies showed diminished gyri in the frontal lobe, persistent cavum septum pellucidum and cavum vergae cyst, and bilateral basal ganglia calcifications. The older patient also had diminishing growth, with height at 99th centile in infancy progressing to 0.2nd centile at 6 years of age. The authors proposed that Primrose syndrome is a progressive condition. </p><p>Cleaver et al. (2019) reported 5 unrelated patients, aged 2 to 13 years, with Primrose syndrome and reviewed 14 other patients with de novo ZBTB20 missense variants to further refine the phenotype. Major clinical features (reported in over 90%) included intellectual disability, most often in moderate range; abnormal findings on MRI, most often abnormalities of the corpus callosum; and a characteristic facial appearance with prominent forehead, deep-set eyes, downslanting and narrow palpebral fissures, small mouth, thin upper lip, pointed chin, and large fleshy ears. Other findings included hearing loss (15/18), hypotonia (14/18), cryptorchidism (6/8), macrocephaly (13/18), behavioral issues (10/18) and abnormal nails (8/14). Findings in more than 80% of adult patients included distal muscle wasting, abnormalities of glucose metabolism, contractures, and ectopic calcification of pinnae. </p>
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<strong>Inheritance</strong>
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<p>The heterozygous mutations in the ZBTB20 gene that were identified in patients with Primrose syndrome by Cordeddu et al. (2014) occurred de novo. </p>
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<strong>Molecular Genetics</strong>
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<p>In 4 unrelated patients with Primrose syndrome, including the patients reported by Mathijssen et al. (2006), Dalal et al. (2010), and Carvalho and Speck-Martins (2011), Cordeddu et al. (2014) performed whole-exome sequencing and identified heterozygosity for de novo missense variants in the ZBTB20 gene (see, e.g., 606025.0001 and 606025.0002); subsequent mutation analysis in 4 more affected individuals, including the patients reported by Battisti et al. (2002) and Posmyk et al. (2011), revealed a de novo heterozygous ZBTB20 missense mutation in each (see, e.g., 606025.0003 and 606025.0004). Functional analysis showed strongly reduced DNA binding for all mutants compared to wildtype, and results were consistent with the mutations having a dominant-negative impact on the wildtype allele. The authors noted that the more severe phenotype seen in Primrose syndrome patients compared to that of patients with 3q13.31 deletion syndrome, who exhibit overlapping but milder features, was in line with a dominant-negative effect of the ZBTB20 mutations compared to the haploinsufficiency that likely underlies the 3q13.31 deletion syndrome. </p><p>By targeted exome sequencing of 275 genes known to be or potentially associated with intellectual disability in a cohort of individuals with mild to severe developmental delay, who were negative for pathogenic CNV by array-CGH, Mattioli et al. (2016) identified a 4-year-old boy with Primrose syndrome who was heterozygous for 2 de novo missense mutations on the same allele of the ZBTB20 gene (606025.0005). </p><p>In a 14-year-old boy with Primrose syndrome, Grimsdottir et al. (2019) identified heterozygosity for a de novo missense mutation in the ZBTB20 gene (H600Q; 606025.0006). The mutation was found by exome sequencing and confirmed by Sanger sequencing. </p><p>In 2 unrelated patients with Primrose syndrome, Stellacci et al. (2018) identified de novo heterozygous mutations in the ZBTB20 gene: the first reported frameshift mutation (c.1024delC; 606025.0007) and a missense mutation (T644I; 606025.0008) in the third zinc finger motif of the protein. The authors noted that previously reported mutations occurred in the first and second zinc finger motifs. Functional data showed that both mutations result in stable but dysfunctional proteins characterized by impaired binding to DNA, consistent with a dominant-negative effect. </p><p>In a 2-year-old boy and an unrelated 27-year-old man with Primrose syndrome, Ferreira et al. (2019) identified heterozygous mutations in the ZBTB20 gene. In the 2-year-old boy, trio exome sequencing identified a novel de novo cys608-to-arg substitution (C608R; 606025.0009). In the 27-year-old man, Sanger sequencing identified a heterozygous met625-to-val (M625V) substitution (M625V; 606025.0010). The M625V variant was not found in the patient's mother or healthy sibs; paternal DNA was unavailable. The variants in both patients occurred in the last coding exon of the ZBTB20 gene and in the second zinc finger domain of the ZBTB20 protein. Neither variant was seen in large population databases; the M625V variant had been previously deposited in ClinVar and dbSNP databases as a likely pathogenic variant, although supporting clinical data were not publicly available. </p><p>In 5 unrelated patients with Primrose syndrome, Cleaver et al. (2019) used trio exome sequencing to identify novel de novo heterozygous pathogenic missense variants in the ZBTB20 gene. Consistent with previous reports, all 5 variants occurred within the C2H2 zinc finger domains. The variants in 2 patients (patients 4 and 5) were in the third zinc finger domain (e.g., 606025.0011), where only 2 pathogenic variants had previously been seen. One patient (patient 4) was mosaic for the variant in blood and saliva. </p>
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<strong>REFERENCES</strong>
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Battisti, C., Dotti, M. T., Cerase, A., Rufa, A., Sicurelli, F., Scarpini, C., Federico, A.
<strong>The Primrose syndrome with progressive neurological involvement and cerebral calcification. (Letter)</strong>
J. Neurol. 249: 1466-1468, 2002.
[PubMed: 12532939]
[Full Text: https://doi.org/10.1007/s00415-002-0850-x]
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Carvalho, D. R., Speck-Martins, C. E.
<strong>Additional features of unique Primrose syndrome phenotype.</strong>
Am. J. Med. Genet. 155A: 1379-1383, 2011.
[PubMed: 21567911]
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Collacott, R. A., O'Malley, B. P., Young, I. D.
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Cordeddu, V., Redeker, B., Stellacci, E., Jongejan, A., Fragale, A., Bradley, T. E. J., Anselmi, M., Ciolfi, A., Cecchetti, S., Muto, V., Bernardini, L., Azage, M., and 15 others.
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Ferreira, L. D., Borges-Medeiros, R. L., Thies, J., Schnur, R. E., Lam, C., de Oliveira, J. R. M.
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Lindor, N. M., Hoffman, A. D., Primrose, D. A.
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Stellacci, E., Steindl, K., Joset, P., Mercurio, L., Anselmi, M., Cecchetti, S., Gogoll, L., Zweier, M., Hackenberg, A., Bocchinfuso, G., Stella, L., Tartaglia, M., Rauch, A.
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