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Entry
- #604757 - CRANIOSYNOSTOSIS 2; CRS2
- OMIM
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<span class="h4">#604757</span>
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<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/604757"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS123100"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
<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=(CRANIOSYNOSTOSIS) OR (MSX2)" class="mim-tip-hint" title="Clinical Trials" 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=3169&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.diseaseinfosearch.org/x/7444" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/gene/msx2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604757[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=1541" 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/35be06db-1725-41a3-a636-1db0caa4c728/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div style="display: table-cell;">Animal Models</div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0061009" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 720817008<br />
<strong>ORPHA:</strong> 1541<br />
<strong>DO:</strong> 0061009<br />
">ICD+</a>
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<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
604757
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<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
CRANIOSYNOSTOSIS 2; CRS2
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<a id="alternativeTitles" class="mim-anchor"></a>
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<em>Alternative titles; symbols</em>
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<h4>
<span class="mim-font">
CRANIOSYNOSTOSIS, BOSTON-TYPE; CSB
</span>
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<br />
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<strong>Phenotype-Gene Relationships</strong>
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<th>
Location
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Phenotype
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<th>
Phenotype <br /> MIM number
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<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
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<th>
Gene/Locus
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<th>
Gene/Locus <br /> MIM number
</th>
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</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/779?start=-3&limit=10&highlight=779">
5q35.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Craniosynostosis 2
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604757"> 604757 </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>
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<td>
<span class="mim-font">
MSX2
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</td>
<td>
<span class="mim-font">
<a href="/entry/123101"> 123101 </a>
</span>
</td>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/604757" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div class="small" style="margin: 5px">
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<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> 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">
- Craniosynostosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57219006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57219006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1421244&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1421244</a>, <a href="https://bioportal.bioontology.org/search?q=C5848303&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848303</a>, <a href="https://bioportal.bioontology.org/search?q=C0010278&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010278</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001363" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001363</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0005458" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005458</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001363" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001363</a>]</span><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 /> -
Turricephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48069004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48069004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5399823&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5399823</a>, <a href="https://bioportal.bioontology.org/search?q=C0030044&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030044</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000262" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000262</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000262" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000262</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=95e02059dac249fc32e95380b6a286cf" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Turricephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=95e02059dac249fc32e95380b6a286cf&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 /> -
Turribrachycephaly <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857484</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000244" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000244</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000244" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000244</a>]</span><br /> -
Dolichcephaly <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5563041&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5563041</a>]</span><br /> -
Trigonocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28740008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28740008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.03</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265535</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000243" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000243</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000243" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000243</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=4906179f9b29c3e7e6e73f5c1c6f3615" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Trigonocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=4906179f9b29c3e7e6e73f5c1c6f3615&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 /> -
Kleeblattschaedel deformity (clover-leaf skull anomaly trilobular skull with craniosynostosis) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230562&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230562</a>]</span><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">
- Forehead retrusion (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230561&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230561</a>]</span><br /> -
Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypotelorism (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44593008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44593008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424711&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424711</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000601" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000601</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000601" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000601</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9e1b9a0002dbf80898b12acc19faf05e" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Closely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9e1b9a0002dbf80898b12acc19faf05e&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 /> -
Myopia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57190000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57190000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027092&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027092</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span><br /> -
Hyperopia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38101003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38101003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span><br /> -
Visual field defects (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12184005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12184005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/368.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887875&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887875</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span><br /> -
Myopia/hyperopia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230559&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230559</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cleft soft palate (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253997002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253997002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0432098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0432098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000185</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000185</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Supernumerary teeth (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8666004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8666004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367534004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367534004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/196273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">196273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/520.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">520.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040457&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040457</a>, <a href="https://bioportal.bioontology.org/search?q=C5441989&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441989</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011069" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011069</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0011067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011067</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011069" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011069</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skull </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Recession of supraorbital rim <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230557&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230557</a>]</span><br /> -
Trilobular skull with craniosynostosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230556&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230556</a>]</span><br /> -
Bicoronal synostosis <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.022" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.022</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4021164&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4021164</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011318" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011318</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011318" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011318</a>]</span><br /> -
Unilateral coronal suture synostosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4023418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4023418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011315</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.02</a>]</span><br /> -
Metopic suture synostosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3280081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3280081</a>]</span><br /> -
Beaten-copper appearance (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230555&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230555</a>]</span><br /> -
Defect of anterior fontanel (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230554&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230554</a>]</span><br /> -
Complex craniosynostosis (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8611000119100" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8611000119100</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3839609&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3839609</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">
- Brachydactyly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43476002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43476002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221357&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221357</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001156" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001156</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001156" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001156</a>]</span><br /> -
Triphalangeal thumb (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205308004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205308004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q74.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q74.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241397&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241397</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001199</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001199" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001199</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=35de1477c268a6d42f86f25677a7609c" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/XR34kRDtve34dB3bQseXeWmKYcyc5kau-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=35de1477c268a6d42f86f25677a7609c&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 /> -
Supination position of thumb (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230552</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">
- Short first metatarsals (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1841688&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1841688</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010105" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010105</a>]</span><br />
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<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
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<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Normal intelligence <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26941006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26941006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423900&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423900</a>]</span><br /> -
Headaches, severe (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2957106&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2957106</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25064002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25064002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R51.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R51.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R51</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.0</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002315</a>]</span><br /> -
Seizures (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br />
</span>
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</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Highly variable intrafamilial expression<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the msh homeobox 2 gene (MSX2, <a href="/entry/123101#0001">123101.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Craniosynostosis
- <a href="/phenotypicSeries/PS123100">PS123100</a>
- 7 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/759?start=-3&limit=10&highlight=759"> 3q24 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616602"> ?Craniosynostosis 6 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616602"> 616602 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600470"> ZIC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600470"> 600470 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/779?start=-3&limit=10&highlight=779"> 5q35.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604757"> Craniosynostosis 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604757"> 604757 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123101"> MSX2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123101"> 123101 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/93?start=-3&limit=10&highlight=93"> 7p21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123100"> Craniosynostosis 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123100"> 123100 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601622"> TWIST1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601622"> 601622 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/329?start=-3&limit=10&highlight=329"> 11p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615529"> {Craniosynostosis 5, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615529"> 615529 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605420"> ALX4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605420"> 605420 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/242?start=-3&limit=10&highlight=242"> 15q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615314"> Craniosynostosis 3 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615314"> 615314 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600480"> TCF12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600480"> 600480 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/315?start=-3&limit=10&highlight=315"> 15q22.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617439"> {Craniosynostosis 7, susceptibility to} </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617439"> 617439 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602931"> SMAD6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602931"> 602931 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/751?start=-3&limit=10&highlight=751"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600775"> Craniosynostosis 4 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600775"> 600775 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611888"> ERF </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611888"> 611888 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<div>
<br />
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<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
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</h4>
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<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that craniosynostosis-2 (CRS2) is caused by heterozygous mutation in the MSX2 gene (<a href="/entry/123101">123101</a>) on chromosome 5q35.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
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<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by <a href="#1" class="mim-tip-reference" title="Fitzpatrick, D. R. &lt;strong&gt;Filling in the gaps in cranial suture biology.&lt;/strong&gt; Nature Genet. 45: 231-232, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23438589/&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;23438589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2557&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="23438589">Fitzpatrick, 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23438589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (<a href="/entry/123100">123100</a>).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#7" class="mim-tip-reference" title="Warman, M. L., Mulliken, J. B., Hayward, P. G., Muller, U. &lt;strong&gt;Newly recognized autosomal dominant disorder with craniosynostosis.&lt;/strong&gt; Am. J. Med. Genet. 46: 444-449, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8357019/&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;8357019&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320460420&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="8357019">Warman et al. (1993)</a> studied a 3-generation American family of English extraction (referred to by <a href="#4" class="mim-tip-reference" title="Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E. &lt;strong&gt;A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993."None>Li et al. (1993)</a> as the Boston family) in which craniosynostosis was segregating in 19 individuals. Although penetrance appeared to be complete, expression varied considerably. Cranial involvement was mild in the grandmother and generally more severe in her affected children and grandchildren. Skull malformations included forehead retrusion, frontal bossing, turribrachycephaly, and the Kleeblattschaedel deformity (cloverleaf skull anomaly; trilobular skull with craniosynostosis). Most affected individuals were myopic or hyperopic and several affected members suffered from severe headaches. Four had a seizure disorder. Intelligence was normal. No hand or foot abnormalities were noted on inspection; radiographic examination in 4 affected individuals demonstrated only short first metatarsals in 3. <a href="#5" class="mim-tip-reference" title="Muller, U., Warman, M. L., Mulliken, J. B., Weber, J. L. &lt;strong&gt;Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.&lt;/strong&gt; Hum. Molec. Genet. 2: 119-122, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8499900/&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;8499900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/2.2.119&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="8499900">Muller et al. (1993)</a> emphasized the consistent finding of recession of the supraorbital region in relation to the anterior surface of the cornea. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8499900+8357019" 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="Florisson, J. M. G., Verkerk, A. J. M. H., Huigh, D., Hoogeboom, A. J. M., Swagemakers, S., Kremer, A., Heijsman, D., Lequin, M. H., Mathijssen, I. M. J., van der Spek, P. J. &lt;strong&gt;Boston type craniosynostosis: report of a second mutation in MSX2.&lt;/strong&gt; Am. J. Med. Genet. 161A: 2626-2633, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23949913/&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;23949913&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36126&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="23949913">Florisson et al. (2013)</a> reported a 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, with 12 affected individuals. Each patient had a distinct skull phenotype, but all had craniosynostosis, variably associated with hypotelorism, forehead retrusion, and/or hand abnormalities. The proband presented at 5 months of age with turricephaly, narrow forehead, downslanting palpebral fissures, and hypotelorism. CT scan showed bilateral coronal synostosis, metopic synostosis, and wormian bones. His fingers were short and broad, but there were no bony abnormalities on x-ray. He underwent frontosupraorbital advancement at age 6 months; at 5 years of age he had normal neurologic development. The proband's 47-year-old father had metopic craniosynostosis resulting in trigonocephaly and hypotelorism, but never underwent surgery; he also had short fingers with normal shape, which x-rays showed was due to shortening of all phalanges. A 22-year-old female cousin had complex craniosynostosis for which she underwent surgery in the first year of life; skull remodeling was later performed due to retrusion of the forehead. She also had short fingers, primarily due to shortening of the distal phalanges, and both thumbs had a supination position. Her 17-year-old brother had mild dolichocephaly and had not undergone surgery; he had normal development without any other anomalies. Other affected family members included the proband's 2 paternal aunts, who had brachycephaly due to premature closure of the coronal sutures with elevation of the sphenoid wings on x-ray; both also exhibited generalized copper-beaten appearance, suggestive of elevated intracranial pressure. The paternal grandfather had unilateral coronal suture synostosis and a bony defect in the area of the anterior fontanel; his brother was known to have turricephaly but declined to participate in the study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23949913" 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 a family linkage study using short tandem repeat polymorphisms (STRPs) (<a href="#8" class="mim-tip-reference" title="Weber, J. L., May, P. E. &lt;strong&gt;Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction.&lt;/strong&gt; Am. J. Hum. Genet. 44: 388-396, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2916582/&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;2916582&lt;/a&gt;]" pmid="2916582">Weber and May, 1989</a>), <a href="#5" class="mim-tip-reference" title="Muller, U., Warman, M. L., Mulliken, J. B., Weber, J. L. &lt;strong&gt;Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.&lt;/strong&gt; Hum. Molec. Genet. 2: 119-122, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8499900/&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;8499900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/2.2.119&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="8499900">Muller et al. (1993)</a> demonstrated that the gene for the disorder in the Boston family is located on 5q. With D5S211, located at 5q34-qter (<a href="#9" class="mim-tip-reference" title="Weber, J. L., Polymeropoulos, M. H., May, P. E., Kwitek, A. E., Xiao, H., McPherson, J. D., Wasmuth, J. J. &lt;strong&gt;Mapping of human chromosome 5 microsatellite DNA polymorphisms.&lt;/strong&gt; Genomics 11: 695-700, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1774070/&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;1774070&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0888-7543(91)90077-r&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="1774070">Weber et al., 1991</a>), they obtained a maximum lod score of 4.8 at a recombination fraction of 0. No linkage was found in this family to markers on chromosome 7 where a gene for the Saethre-Chotzen syndrome (<a href="/entry/101400">101400</a>) has been mapped. Supporting the assignment of a locus for a form of craniosynostosis to 5q was the observation of craniosynostosis in an infant with partial trisomy of distal 5q (<a href="#6" class="mim-tip-reference" title="Van der Burgt, C. J. A. M., Merkx, G. F. M., Janssen, A. H., Mulder, J. C., Suijkerbuijk, R. F., Smeets, D. F. C. M. &lt;strong&gt;Partial trisomy for 5q and monosomy for 12p in a liveborn child as a result of a complex five breakpoint chromosome rearrangement in a parent.&lt;/strong&gt; J. Med. Genet. 29: 739-741, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1433237/&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;1433237&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.29.10.739&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="1433237">Van der Burgt et al., 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1433237+8499900+2916582+1774070" 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 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, <a href="#2" class="mim-tip-reference" title="Florisson, J. M. G., Verkerk, A. J. M. H., Huigh, D., Hoogeboom, A. J. M., Swagemakers, S., Kremer, A., Heijsman, D., Lequin, M. H., Mathijssen, I. M. J., van der Spek, P. J. &lt;strong&gt;Boston type craniosynostosis: report of a second mutation in MSX2.&lt;/strong&gt; Am. J. Med. Genet. 161A: 2626-2633, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23949913/&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;23949913&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36126&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="23949913">Florisson et al. (2013)</a> performed multipoint linkage analysis and obtained 4 linkage peaks with maximum lod scores between 2 and 2.5, including a 5.9-Mb interval on chromosome 5q35. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23949913" 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>To determine whether expression of the MXS2 gene, which maps to the same region of chromosome 5 as craniosynostosis-2, is consistent with its being a candidate gene for the phenotype, <a href="#4" class="mim-tip-reference" title="Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E. &lt;strong&gt;A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993."None>Li et al. (1993)</a> demonstrated by in situ hybridization that mouse Msx2 transcripts are present in osteoblasts adjacent to calvarial sutures during mouse embryonic and postnatal development. In addition, <a href="#4" class="mim-tip-reference" title="Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E. &lt;strong&gt;A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993."None>Li et al. (1993)</a> found that a (CA)n polymorphism within the MSX2 gene segregated with craniosynostosis in the Boston family studied by <a href="#7" class="mim-tip-reference" title="Warman, M. L., Mulliken, J. B., Hayward, P. G., Muller, U. &lt;strong&gt;Newly recognized autosomal dominant disorder with craniosynostosis.&lt;/strong&gt; Am. J. Med. Genet. 46: 444-449, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8357019/&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;8357019&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320460420&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="8357019">Warman et al. (1993)</a> and <a href="#5" class="mim-tip-reference" title="Muller, U., Warman, M. L., Mulliken, J. B., Weber, J. L. &lt;strong&gt;Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.&lt;/strong&gt; Hum. Molec. Genet. 2: 119-122, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8499900/&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;8499900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/2.2.119&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="8499900">Muller et al. (1993)</a>; no recombination was observed, giving a maximum lod score of 4.80. All affected members were found to have substitution of histidine for proline at amino acid position 7 of the homeodomain (P148H; <a href="/entry/123101#0001">123101.0001</a>); the mutation was absent in all unaffected members of the family and 68 controls. This proline residue is conserved in all known MSX genes in organisms as diverse as insects and mammals. <a href="#4" class="mim-tip-reference" title="Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E. &lt;strong&gt;A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993."None>Li et al. (1993)</a> claimed that this was the first report of a mutation in a homeobox gene associated with a human disorder. See <a href="#3" class="mim-tip-reference" title="Jabs, E. W., Muller, U., Li, X., Ma, L., Luo, W., Haworth, I. S., Klisak, I., Sparkes, R., Warman, M. L., Mulliken, J. B., Snead, M. L., Maxson, R. &lt;strong&gt;A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.&lt;/strong&gt; Cell 75: 443-450, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8106171/&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;8106171&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0092-8674(93)90379-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8106171">Jabs et al. (1993)</a> for the full report. This is a good example of identification of the defect in a disorder by the candidate gene approach. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8106171+8499900+8357019" 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 7 affected members of a 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, <a href="#2" class="mim-tip-reference" title="Florisson, J. M. G., Verkerk, A. J. M. H., Huigh, D., Hoogeboom, A. J. M., Swagemakers, S., Kremer, A., Heijsman, D., Lequin, M. H., Mathijssen, I. M. J., van der Spek, P. J. &lt;strong&gt;Boston type craniosynostosis: report of a second mutation in MSX2.&lt;/strong&gt; Am. J. Med. Genet. 161A: 2626-2633, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23949913/&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;23949913&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36126&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="23949913">Florisson et al. (2013)</a> identified heterozygosity for a pro148-to-leu mutation (P148L; <a href="/entry/123101#0009">123101.0009</a>) in the MSX2 gene. The mutation altered the same proline as that identified by <a href="#4" class="mim-tip-reference" title="Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E. &lt;strong&gt;A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993."None>Li et al. (1993)</a> in the Boston family with CRS2. The proband and his father, who were the only patients to manifest osteopoikilosis (see <a href="/entry/166700">166700</a>), were also heterozygous for a deletion in the LEMD3 gene (<a href="/entry/607844">607844</a>). The LEMD3 mutation appeared to have arisen de novo in the father, and the presence of osteopoikilosis in the 2 patients was considered to be a coincidental anomaly unrelated to the craniosynostosis phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23949913" 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="Fitzpatrick2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fitzpatrick, D. R.
<strong>Filling in the gaps in cranial suture biology.</strong>
Nature Genet. 45: 231-232, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23438589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23438589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23438589" 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.2557" target="_blank">Full Text</a>]
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<a id="Florisson2013" class="mim-anchor"></a>
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<p class="mim-text-font">
Florisson, J. M. G., Verkerk, A. J. M. H., Huigh, D., Hoogeboom, A. J. M., Swagemakers, S., Kremer, A., Heijsman, D., Lequin, M. H., Mathijssen, I. M. J., van der Spek, P. J.
<strong>Boston type craniosynostosis: report of a second mutation in MSX2.</strong>
Am. J. Med. Genet. 161A: 2626-2633, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23949913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23949913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23949913" 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.36126" target="_blank">Full Text</a>]
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<a id="Jabs1993" class="mim-anchor"></a>
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<p class="mim-text-font">
Jabs, E. W., Muller, U., Li, X., Ma, L., Luo, W., Haworth, I. S., Klisak, I., Sparkes, R., Warman, M. L., Mulliken, J. B., Snead, M. L., Maxson, R.
<strong>A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.</strong>
Cell 75: 443-450, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8106171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8106171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8106171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0092-8674(93)90379-5" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
<a id="Li1993" class="mim-anchor"></a>
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Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E.
<strong>A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)</strong>
Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993.
</p>
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<a id="Muller1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Muller, U., Warman, M. L., Mulliken, J. B., Weber, J. L.
<strong>Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.</strong>
Hum. Molec. Genet. 2: 119-122, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/2.2.119" target="_blank">Full Text</a>]
</p>
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<a id="6" class="mim-anchor"></a>
<a id="Van der Burgt1992" class="mim-anchor"></a>
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<p class="mim-text-font">
Van der Burgt, C. J. A. M., Merkx, G. F. M., Janssen, A. H., Mulder, J. C., Suijkerbuijk, R. F., Smeets, D. F. C. M.
<strong>Partial trisomy for 5q and monosomy for 12p in a liveborn child as a result of a complex five breakpoint chromosome rearrangement in a parent.</strong>
J. Med. Genet. 29: 739-741, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1433237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1433237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1433237" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.29.10.739" target="_blank">Full Text</a>]
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Warman, M. L., Mulliken, J. B., Hayward, P. G., Muller, U.
<strong>Newly recognized autosomal dominant disorder with craniosynostosis.</strong>
Am. J. Med. Genet. 46: 444-449, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357019</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8357019" 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.1320460420" target="_blank">Full Text</a>]
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<a id="Weber1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Weber, J. L., May, P. E.
<strong>Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction.</strong>
Am. J. Hum. Genet. 44: 388-396, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2916582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2916582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2916582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Weber, J. L., Polymeropoulos, M. H., May, P. E., Kwitek, A. E., Xiao, H., McPherson, J. D., Wasmuth, J. J.
<strong>Mapping of human chromosome 5 microsatellite DNA polymorphisms.</strong>
Genomics 11: 695-700, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1774070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0888-7543(91)90077-r" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 01/15/2016
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Marla J. F. O'Neill - updated : 7/18/2013
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Victor A. McKusick : 3/29/2000
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carol : 04/19/2017
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carol : 01/15/2016<br>carol : 10/16/2015<br>carol : 7/18/2013<br>carol : 7/18/2013<br>carol : 3/16/2010<br>terry : 3/18/2004<br>carol : 3/29/2000<br>carol : 3/29/2000
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<h3>
<span class="mim-font">
<strong>#</strong> 604757
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<span class="mim-font">
CRANIOSYNOSTOSIS 2; CRS2
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<span class="mim-font">
<em>Alternative titles; symbols</em>
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<span class="mim-font">
CRANIOSYNOSTOSIS, BOSTON-TYPE; CSB
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<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 720817008; &nbsp;
<strong>ORPHA:</strong> 1541; &nbsp;
<strong>DO:</strong> 0061009; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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<th>
Location
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Phenotype
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Phenotype <br /> MIM number
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<th>
Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
5q35.2
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Craniosynostosis 2
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<span class="mim-font">
604757
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<span class="mim-font">
Autosomal dominant
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<span class="mim-font">
3
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MSX2
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<span class="mim-font">
123101
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that craniosynostosis-2 (CRS2) is caused by heterozygous mutation in the MSX2 gene (123101) on chromosome 5q35.</p>
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<span class="mim-font">
<strong>Description</strong>
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<p>Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). </p><p>For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).</p>
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<span class="mim-font">
<strong>Clinical Features</strong>
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<p>Warman et al. (1993) studied a 3-generation American family of English extraction (referred to by Li et al. (1993) as the Boston family) in which craniosynostosis was segregating in 19 individuals. Although penetrance appeared to be complete, expression varied considerably. Cranial involvement was mild in the grandmother and generally more severe in her affected children and grandchildren. Skull malformations included forehead retrusion, frontal bossing, turribrachycephaly, and the Kleeblattschaedel deformity (cloverleaf skull anomaly; trilobular skull with craniosynostosis). Most affected individuals were myopic or hyperopic and several affected members suffered from severe headaches. Four had a seizure disorder. Intelligence was normal. No hand or foot abnormalities were noted on inspection; radiographic examination in 4 affected individuals demonstrated only short first metatarsals in 3. Muller et al. (1993) emphasized the consistent finding of recession of the supraorbital region in relation to the anterior surface of the cornea. </p><p>Florisson et al. (2013) reported a 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, with 12 affected individuals. Each patient had a distinct skull phenotype, but all had craniosynostosis, variably associated with hypotelorism, forehead retrusion, and/or hand abnormalities. The proband presented at 5 months of age with turricephaly, narrow forehead, downslanting palpebral fissures, and hypotelorism. CT scan showed bilateral coronal synostosis, metopic synostosis, and wormian bones. His fingers were short and broad, but there were no bony abnormalities on x-ray. He underwent frontosupraorbital advancement at age 6 months; at 5 years of age he had normal neurologic development. The proband's 47-year-old father had metopic craniosynostosis resulting in trigonocephaly and hypotelorism, but never underwent surgery; he also had short fingers with normal shape, which x-rays showed was due to shortening of all phalanges. A 22-year-old female cousin had complex craniosynostosis for which she underwent surgery in the first year of life; skull remodeling was later performed due to retrusion of the forehead. She also had short fingers, primarily due to shortening of the distal phalanges, and both thumbs had a supination position. Her 17-year-old brother had mild dolichocephaly and had not undergone surgery; he had normal development without any other anomalies. Other affected family members included the proband's 2 paternal aunts, who had brachycephaly due to premature closure of the coronal sutures with elevation of the sphenoid wings on x-ray; both also exhibited generalized copper-beaten appearance, suggestive of elevated intracranial pressure. The paternal grandfather had unilateral coronal suture synostosis and a bony defect in the area of the anterior fontanel; his brother was known to have turricephaly but declined to participate in the study. </p>
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<h4>
<span class="mim-font">
<strong>Mapping</strong>
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</h4>
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<span class="mim-text-font">
<p>In a family linkage study using short tandem repeat polymorphisms (STRPs) (Weber and May, 1989), Muller et al. (1993) demonstrated that the gene for the disorder in the Boston family is located on 5q. With D5S211, located at 5q34-qter (Weber et al., 1991), they obtained a maximum lod score of 4.8 at a recombination fraction of 0. No linkage was found in this family to markers on chromosome 7 where a gene for the Saethre-Chotzen syndrome (101400) has been mapped. Supporting the assignment of a locus for a form of craniosynostosis to 5q was the observation of craniosynostosis in an infant with partial trisomy of distal 5q (Van der Burgt et al., 1992). </p><p>In a 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, Florisson et al. (2013) performed multipoint linkage analysis and obtained 4 linkage peaks with maximum lod scores between 2 and 2.5, including a 5.9-Mb interval on chromosome 5q35. </p>
</span>
<div>
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<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
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</h4>
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<span class="mim-text-font">
<p>To determine whether expression of the MXS2 gene, which maps to the same region of chromosome 5 as craniosynostosis-2, is consistent with its being a candidate gene for the phenotype, Li et al. (1993) demonstrated by in situ hybridization that mouse Msx2 transcripts are present in osteoblasts adjacent to calvarial sutures during mouse embryonic and postnatal development. In addition, Li et al. (1993) found that a (CA)n polymorphism within the MSX2 gene segregated with craniosynostosis in the Boston family studied by Warman et al. (1993) and Muller et al. (1993); no recombination was observed, giving a maximum lod score of 4.80. All affected members were found to have substitution of histidine for proline at amino acid position 7 of the homeodomain (P148H; 123101.0001); the mutation was absent in all unaffected members of the family and 68 controls. This proline residue is conserved in all known MSX genes in organisms as diverse as insects and mammals. Li et al. (1993) claimed that this was the first report of a mutation in a homeobox gene associated with a human disorder. See Jabs et al. (1993) for the full report. This is a good example of identification of the defect in a disorder by the candidate gene approach. </p><p>In 7 affected members of a 4-generation Bosnian family segregating autosomal dominant multiple-suture craniosynostosis, Florisson et al. (2013) identified heterozygosity for a pro148-to-leu mutation (P148L; 123101.0009) in the MSX2 gene. The mutation altered the same proline as that identified by Li et al. (1993) in the Boston family with CRS2. The proband and his father, who were the only patients to manifest osteopoikilosis (see 166700), were also heterozygous for a deletion in the LEMD3 gene (607844). The LEMD3 mutation appeared to have arisen de novo in the father, and the presence of osteopoikilosis in the 2 patients was considered to be a coincidental anomaly unrelated to the craniosynostosis phenotype. </p>
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
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<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Fitzpatrick, D. R.
<strong>Filling in the gaps in cranial suture biology.</strong>
Nature Genet. 45: 231-232, 2013.
[PubMed: 23438589]
[Full Text: https://doi.org/10.1038/ng.2557]
</p>
</li>
<li>
<p class="mim-text-font">
Florisson, J. M. G., Verkerk, A. J. M. H., Huigh, D., Hoogeboom, A. J. M., Swagemakers, S., Kremer, A., Heijsman, D., Lequin, M. H., Mathijssen, I. M. J., van der Spek, P. J.
<strong>Boston type craniosynostosis: report of a second mutation in MSX2.</strong>
Am. J. Med. Genet. 161A: 2626-2633, 2013.
[PubMed: 23949913]
[Full Text: https://doi.org/10.1002/ajmg.a.36126]
</p>
</li>
<li>
<p class="mim-text-font">
Jabs, E. W., Muller, U., Li, X., Ma, L., Luo, W., Haworth, I. S., Klisak, I., Sparkes, R., Warman, M. L., Mulliken, J. B., Snead, M. L., Maxson, R.
<strong>A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis.</strong>
Cell 75: 443-450, 1993.
[PubMed: 8106171]
[Full Text: https://doi.org/10.1016/0092-8674(93)90379-5]
</p>
</li>
<li>
<p class="mim-text-font">
Li, X., Ma, L., Snead, M., Haworth, I., Sparkes, R., Jackson, C., Warman, M., Mulliken, J., Maxson, R., Muller, U., Jabs, E.
<strong>A mutation in the homeodomain of the MSX2 gene in a family affected with craniosynostosis, Boston type. (Abstract)</strong>
Am. J. Hum. Genet. 53 (suppl.): A213 only, 1993.
</p>
</li>
<li>
<p class="mim-text-font">
Muller, U., Warman, M. L., Mulliken, J. B., Weber, J. L.
<strong>Assignment of a gene locus involved in craniosynostosis to chromosome 5qter.</strong>
Hum. Molec. Genet. 2: 119-122, 1993.
[PubMed: 8499900]
[Full Text: https://doi.org/10.1093/hmg/2.2.119]
</p>
</li>
<li>
<p class="mim-text-font">
Van der Burgt, C. J. A. M., Merkx, G. F. M., Janssen, A. H., Mulder, J. C., Suijkerbuijk, R. F., Smeets, D. F. C. M.
<strong>Partial trisomy for 5q and monosomy for 12p in a liveborn child as a result of a complex five breakpoint chromosome rearrangement in a parent.</strong>
J. Med. Genet. 29: 739-741, 1992.
[PubMed: 1433237]
[Full Text: https://doi.org/10.1136/jmg.29.10.739]
</p>
</li>
<li>
<p class="mim-text-font">
Warman, M. L., Mulliken, J. B., Hayward, P. G., Muller, U.
<strong>Newly recognized autosomal dominant disorder with craniosynostosis.</strong>
Am. J. Med. Genet. 46: 444-449, 1993.
[PubMed: 8357019]
[Full Text: https://doi.org/10.1002/ajmg.1320460420]
</p>
</li>
<li>
<p class="mim-text-font">
Weber, J. L., May, P. E.
<strong>Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction.</strong>
Am. J. Hum. Genet. 44: 388-396, 1989.
[PubMed: 2916582]
</p>
</li>
<li>
<p class="mim-text-font">
Weber, J. L., Polymeropoulos, M. H., May, P. E., Kwitek, A. E., Xiao, H., McPherson, J. D., Wasmuth, J. J.
<strong>Mapping of human chromosome 5 microsatellite DNA polymorphisms.</strong>
Genomics 11: 695-700, 1991.
[PubMed: 1774070]
[Full Text: https://doi.org/10.1016/0888-7543(91)90077-r]
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Marla J. F. O&#x27;Neill - updated : 01/15/2016<br>Marla J. F. O&#x27;Neill - updated : 7/18/2013
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Victor A. McKusick : 3/29/2000
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</div>
</div>
<div class="modal-footer">
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
</div>
</div>
</div>
</div>
</div>
</body>
</html>
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