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<title>
Entry
- #606408 - EHLERS-DANLOS SYNDROME, CLASSIC-LIKE, 1; EDSCLL1
- OMIM
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<span class="h4">#606408</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/606408"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS130000"> <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="#otherFeatures">Other Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#references"><strong>References</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=EHLERS-DANLOS SYNDROME, CLASSIC-LIKE" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19142&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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</div>
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</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 778022009<br />
<strong>ORPHA:</strong> 230839<br />
<strong>DO:</strong> 0080731<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
606408
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
EHLERS-DANLOS SYNDROME, CLASSIC-LIKE, 1; EDSCLL1
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
EHLERS-DANLOS SYNDROME, CLASSIC-LIKE; EDSCLL<br />
EHLERS-DANLOS SYNDROME DUE TO TENASCIN-X DEFICIENCY<br />
EDS DUE TO TNX DEFICIENCY<br />
TNX DEFICIENCY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/351?start=-3&limit=10&highlight=351">
6p21.33-p21.32
</a>
</span>
</td>
<td>
<span class="mim-font">
Ehlers-Danlos syndrome, classic-like, 1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606408"> 606408 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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">
TNXB
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600985"> 600985 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
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<a href="/clinicalSynopsis/606408" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS130000" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/606408" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/606408" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Quadricuspid aortic valve (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253611000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253611000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0345002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0345002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031655" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031655</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031655" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031655</a>]</span><br /> -
Mitral valve prolapse (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409712001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409712001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8074002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8074002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026267&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026267</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001634" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001634</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001634" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001634</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hiatus hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84089009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84089009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3489393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3489393</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002036" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002036</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002036" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002036</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Genitalia (Female) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Ambiguous genitalia (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/21321009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">21321009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q56.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q56.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000062" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000062</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000062" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000062</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Female) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Bicornuate uterus (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31401003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31401003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/289637001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">289637001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q51.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q51.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.34" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.34</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266387&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266387</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000813" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000813</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000813" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000813</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Single kidney (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266294</a>, <a href="https://bioportal.bioontology.org/search?q=C1849176&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849176</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000122" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000122</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000122" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000122</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Bladder </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vesicoureteral reflux (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197811007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197811007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N13.70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N13.70</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N13.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N13.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/593.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">593.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042580&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042580</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000076</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000076</a>]</span><br /> -
Urethral prolapse (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12068006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12068006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/772794003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">772794003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N81.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N81.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/599.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">599.5</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/618.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">618.03</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238502&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238502</a>, <a href="https://bioportal.bioontology.org/search?q=C0156287&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0156287</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100821" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100821</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> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Joint hypermobility <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/788453008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">788453008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1862377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1862377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br /> -
Arthralgia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57676002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57676002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M25.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M25.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/719.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/719.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003862</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span><br /> -
Joint subluxation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26396009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26396009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263031003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263031003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0332768&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332768</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032153" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032153</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032153" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032153</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hyperextensible skin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241074&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241074</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000974</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000974</a>]</span><br /> -
Easy bruisability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/425075004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">425075004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/424131007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">424131007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000978" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000978</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000978" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000978</a>]</span><br /> -
No scarring <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851824</a>]</span><br /> -
Velvety skin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241178&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241178</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000977" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000977</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000977" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000977</a>]</span><br /> -
Normal wound healing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1863751&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1863751</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Proximal muscle weakness (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249939004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221629</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span><br /> -
Proximal muscle atrophy (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850794</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007126</a>]</span><br /> -
Myopathic pattern seen on EMG (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4015455&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4015455</a>]</span><br /> -
Internal nuclei seen on biopsy (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012932&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012932</a>]</span><br /> -
Muscle fiber splitting (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836057&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836057</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003555" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003555</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003555" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003555</a>]</span><br /> -
Increased connective tissue (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866021</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span><br /> -
Disruption plasma membrane (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012935</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Elevated serum 17-hydroxyprogesterone level (seen in patients with contiguous gene defect) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551835</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Tenascin X deficiency (serum and fibroblasts) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2676306&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2676306</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Some patients may present with myopathic features<br /> -
Some patients have a contiguous gene defect involving both the CYP21A2 (<a href="/entry/613815">613815</a>) and the TNXB (<a href="/entry/600985">600985</a>) genes<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 tenascin XB gene (TNXB, <a href="/entry/600985#0001">600985.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Ehlers-Danlos syndrome
- <a href="/phenotypicSeries/PS130000">PS130000</a>
- 23 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/1/33?start=-3&limit=10&highlight=33"> 1p36.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615349"> Ehlers-Danlos syndrome, spondylodysplastic type, 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/615349"> 615349 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615291"> B3GALT6 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615291"> 615291 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/162?start=-3&limit=10&highlight=162"> 1p36.22 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/225400"> Ehlers-Danlos syndrome, kyphoscoliotic type, 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/225400"> 225400 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/153454"> PLOD1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/153454"> 153454 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/854?start=-3&limit=10&highlight=854"> 2q32.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130050"> Ehlers-Danlos syndrome, vascular type </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/130050"> 130050 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120180"> COL3A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120180"> 120180 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/855?start=-3&limit=10&highlight=855"> 2q32.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130010"> Ehlers-Danlos syndrome, classic type, 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/130010"> 130010 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120190"> COL5A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120190"> 120190 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/523?start=-3&limit=10&highlight=523"> 4q27 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614170"> Brittle cornea syndrome 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/614170"> 614170 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614161"> PRDM5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614161"> 614161 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/817?start=-3&limit=10&highlight=817"> 5q35.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130070"> Ehlers-Danlos syndrome, spondylodysplastic type, 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/130070"> 130070 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604327"> B4GALT7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604327"> 604327 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/829?start=-3&limit=10&highlight=829"> 5q35.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/225410"> Ehlers-Danlos syndrome, dermatosparaxis type </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/225410"> 225410 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604539"> ADAMTS2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604539"> 604539 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/351?start=-3&limit=10&highlight=351"> 6p21.33-p21.32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606408"> Ehlers-Danlos syndrome, classic-like, 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/606408"> 606408 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600985"> TNXB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600985"> 600985 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/650?start=-3&limit=10&highlight=650"> 6q13-q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616471"> Bethlem myopathy 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/616471"> 616471 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120320"> COL12A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120320"> 120320 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/798?start=-3&limit=10&highlight=798"> 6q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615539"> Ehlers-Danlos syndrome, musculocontractural type 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/615539"> 615539 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605942"> DSE </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605942"> 605942 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/1032?start=-3&limit=10&highlight=1032"> 6q27 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620865"> ?Ehlers-Danlos syndrome, classic-like, 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/620865"> 620865 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188061"> THBS2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188061"> 188061 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/159?start=-3&limit=10&highlight=159"> 7p14.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614557"> Ehlers-Danlos syndrome, kyphoscoliotic type, 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/614557"> 614557 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614505"> FKBP14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614505"> 614505 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/227?start=-3&limit=10&highlight=227"> 7p13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618000"> Ehlers-Danlos syndrome, classic-like, 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/618000"> 618000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602981"> AEBP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602981"> 602981 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/225320"> Ehlers-Danlos syndrome, cardiac valvular type </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/225320"> 225320 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> COL1A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617821"> Ehlers-Danlos syndrome, arthrochalasia type, 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/617821"> 617821 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> COL1A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/629?start=-3&limit=10&highlight=629"> 9q34.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130000"> Ehlers-Danlos syndrome, classic type, 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/130000"> 130000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120215"> COL5A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120215"> 120215 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/363?start=-3&limit=10&highlight=363"> 11p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612350"> Ehlers-Danlos syndrome, spondylodysplastic type, 3 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/612350"> 612350 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608735"> SLC39A13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608735"> 608735 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/89?start=-3&limit=10&highlight=89"> 12p13.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617174"> Ehlers-Danlos syndrome, periodontal type, 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/617174"> 617174 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120580"> C1S </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120580"> 120580 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/90?start=-3&limit=10&highlight=90"> 12p13.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130080"> Ehlers-Danlos syndrome, periodontal type, 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/130080"> 130080 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613785"> C1R </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613785"> 613785 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/100?start=-3&limit=10&highlight=100"> 15q15.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601776"> Ehlers-Danlos syndrome, musculocontractural type 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/601776"> 601776 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608429"> CHST14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608429"> 608429 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/727?start=-3&limit=10&highlight=727"> 16q24.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/229200"> Brittle cornea syndrome 1 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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/229200"> 229200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612078"> ZNF469 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612078"> 612078 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130060"> Ehlers-Danlos syndrome, arthrochalasia type, 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/130060"> 130060 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> COL1A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
Not Mapped
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130020"> Ehlers-Danlos syndrome, hypermobility type </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">
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130020"> 130020 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130020"> EDSHMB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130020"> 130020 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<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>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because Ehlers-Danlos syndrome classic-like-1 (EDSCLL1) is caused by homozygous or compound heterozygous mutation in the tenascin-XB gene (TNXB; <a href="/entry/600985">600985</a>) on chromosome 6p21.</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>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Ehlers-Danlos syndrome classic-like-1 (EDSCLL1) is a connective tissue disorder characterized by hyperextensible skin, hypermobile joints, and tissue fragility (<a href="#1" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D. &lt;strong&gt;Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 59 (suppl.): A16, 1996."None>Burch et al., 1996</a>).</p><p><strong><em>Genetic Heterogeneity of Classic-Like Ehlers-Danlos Syndrome</em></strong></p><p>
EDSCLL2 (<a href="/entry/618000">618000</a>) is caused by mutation in the AEBP1 gene (<a href="/entry/602981">602981</a>) on chromosome 7p13, and EDSCLL3 (<a href="/entry/620865">620865</a>) is caused by mutation in the THBS2 gene (<a href="/entry/188061">188061</a>) on chromosome 6q27.</p><p>For a discussion of the classification of EDS, see <a href="/entry/130000">130000</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>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#1" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D. &lt;strong&gt;Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 59 (suppl.): A16, 1996."None>Burch et al. (1996)</a> reported a 25-year-old man with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (<a href="/entry/201910">201910</a>), associated with a classic Ehlers-Danlos syndrome (see <a href="/entry/130000">130000</a>)-like phenotype, consisting of hyperextensible skin and joints, patellar chondromalacia, and easy bruising. In their full report, <a href="#2" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., Bristow, J. &lt;strong&gt;Tenascin-X deficiency is associated with Ehlers-Danlos syndrome.&lt;/strong&gt; Nature Genet. 17: 104-108, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9288108/&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;9288108&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0997-104&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="9288108">Burch et al. (1997)</a> described atypical histologic findings that suggested a novel mechanism of disease in their proband: the most striking findings were abnormal elastin (<a href="/entry/130160">130160</a>) bodies beneath the dermal-epidermal junction, a diffuse increase in perivascular matrix, and uneven packing of the myelin sheaths of peripheral nerves. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288108" 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>To investigate the role of tenascins in EDS, <a href="#9" class="mim-tip-reference" title="Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J. &lt;strong&gt;A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.&lt;/strong&gt; New Eng. J. Med. 345: 1167-1175, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11642233/&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;11642233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa002939&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="11642233">Schalkwijk et al. (2001)</a> screened serum samples from 151 patients with the classic, hypermobility, or vascular types of EDS for the presence of tenascin-X and tenascin-C (<a href="/entry/187380">187380</a>) by enzyme-linked immunosorbent assay. The same assays were done in 75 patients with psoriasis, 93 patients with rheumatoid arthritis, and 21 healthy persons. Absence of tenascin-X from the serum was found in 5 unrelated patients, all of whom had recessive EDS and 1 of whom also had CAH. All 5 tenascin-X-deficient patients and 3 clinically affected tenascin-X-deficient sibs had hyperelastic skin and hypermobile joints, fulfilling major diagnostic criteria for classic EDS. Minor diagnostic criteria supporting the diagnosis of classic EDS in these patients and their affected sibs included easy bruising in all, velvety skin in 7, joint pain in 2, and multiple subluxations in 3. Although the findings were similar to those of classic EDS, all tenascin-X-deficient patients lacked atrophic scars, a major diagnostic criteria for classic EDS. Delayed wound healing, which is also common in classic EDS, was not present in any of these patients, although it was noted in the tenascin-X-deficient patient reported by <a href="#2" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., Bristow, J. &lt;strong&gt;Tenascin-X deficiency is associated with Ehlers-Danlos syndrome.&lt;/strong&gt; Nature Genet. 17: 104-108, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9288108/&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;9288108&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0997-104&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="9288108">Burch et al. (1997)</a>. However, it was possible that treatment with glucocorticoids for congenital adrenal hyperplasia in that patient may have played a role in delayed wound healing. The tenascin-X-deficient patients reported by <a href="#9" class="mim-tip-reference" title="Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J. &lt;strong&gt;A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.&lt;/strong&gt; New Eng. J. Med. 345: 1167-1175, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11642233/&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;11642233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa002939&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="11642233">Schalkwijk et al. (2001)</a> also had a range of additional clinical findings not typically associated with EDS, including congenital adrenal hyperplasia, spina bifida occulta, mitral valve prolapse, stroke, gastrointestinal bleeding, and premature arteriosclerosis. It was not clear whether these additional disorders were related to tenascin-X deficiency. None of the parents of the 5 patients with tenascin-X deficiency were related, and none of the 4 parents available for study had clinical signs of EDS. The authors identified mutations in the TNX gene in all 5 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9288108+11642233" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Lindor, N. M., Bristow, J. &lt;strong&gt;Tenascin-X deficiency in autosomal recessive Ehlers-Danlos syndrome.&lt;/strong&gt; Am. J. Med. Genet. 135A: 75-80, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15793839/&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;15793839&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30671&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="15793839">Lindor and Bristow (2005)</a> described 2 unrelated patients with complete deficiency of tenascin-X who had marked skin hyperextensibility, easy bruising, and joint laxity. Unlike classic EDS patients, they did not have atrophic scarring or poor wound healing. Significant medical problems occurring in these individuals included severe diverticular intestinal disease with ruptured diverticula, pancolonic diverticulitis, and rectal prolapse, mitral valve prolapse requiring valve replacement, and obstructive airway disease. One patient had 3 daughters, presumed heterozygotes, who had minimal clinical expression of a tenascin-X deficiency phenotype and did not meet the diagnostic criteria for EDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15793839" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Chen, W., Kim, M. S., Shanbhag, S., Arai, A., VanRyzin, C., McDonnell, N. B., Merke, D. P. &lt;strong&gt;The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects.&lt;/strong&gt; Am. J. Med. Genet. 149A: 2803-2808, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19921645/&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;19921645&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19921645[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33092&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="19921645">Chen et al. (2009)</a> reported an 8-year-old 46,XX girl, born with ambiguous genitalia, bicornuate uterus, single kidney, and grade III vesicoureteral reflux, who was found to have 21-hydroxylase deficiency. Examination at 8 years of age revealed bifid uvula, single palmar crease on the left hand, normal skin, mild arachnodactyly, and hyperextensible joints with a Beighton score of 8/9. Her mother, who had a history of urethral prolapse and hiatus hernia, also had hyperextensible joints (Beighton score, 7/9), and her maternal grandfather had hyperextensible thumbs, whereas her father had a Beighton score of 0/9. Cardiac MRI revealed a quadricuspid aortic valve in the proband; her mother had mild mitral valve prolapse and trace regurgitation by transthoracic echocardiogram. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19921645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Voermans, N. C., van Alfen, N., Pillen, S., Lammens, M., Schalkwijk, J., Zwarts, M. J., van Rooij, I. A., Hamel, B. C. J., van Engelen, B. G. &lt;strong&gt;Neuromuscular involvement in various types of Ehlers-Danlos syndrome.&lt;/strong&gt; Ann. Neurol. 65: 687-697, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19557868/&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;19557868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21643&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="19557868">Voermans et al. (2009)</a> performed a cross-sectional study on the presence of neuromuscular symptoms in 40 patients with various forms of EDS. Ten patients each were analyzed with classic EDS (see <a href="/entry/130000">130000</a>), vascular EDS (<a href="/entry/130050">130050</a>), hypermobility EDS (<a href="/entry/130020">130020</a>), and TNX-deficient EDS. Overall, those with classic EDS and TNX-deficient EDS reported the most neuromuscular involvement, with muscle weakness, hypotonia, myalgia, easy fatigability, and intermittent paresthesias, although patients in all groups reported these features. Physical examination showed mild to moderate muscle weakness (85%) and reduction of vibration sense (60%) across all groups. Nerve conduction studies demonstrated axonal polyneuropathy in 5 (13%) of 39 patients. Needle electromyography showed myopathic EMG features in 9 (26%) and a mixed neurogenic-myopathic pattern in 21 (60%) of 35 patients. Muscle ultrasound showed increased echo intensity in 19 (48%) and atrophy in 20 (50%) of 40 patients. Mild myopathic features were seen on muscle biopsy of 5 (28%) of 18 patients. Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. <a href="#12" class="mim-tip-reference" title="Voermans, N. C., van Alfen, N., Pillen, S., Lammens, M., Schalkwijk, J., Zwarts, M. J., van Rooij, I. A., Hamel, B. C. J., van Engelen, B. G. &lt;strong&gt;Neuromuscular involvement in various types of Ehlers-Danlos syndrome.&lt;/strong&gt; Ann. Neurol. 65: 687-697, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19557868/&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;19557868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21643&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="19557868">Voermans et al. (2009)</a> postulated that abnormalities in muscle or nerve extracellular matrix may underlie these findings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19557868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Penisson-Besnier, I., Allamand, V., Beurrier, P., Martin, L., Schalkwijk, J., van Vlijmen-Willems, I., Gartioux, C., Malfait, F., Syx, D., Macchi, L., Marcorelles, P., Arbeille, B., Croue, A., De Paepe, A., Dubas, F. &lt;strong&gt;Compound heterozygous mutations of the TNXB gene cause primary myopathy.&lt;/strong&gt; Neuromusc. Disord. 23: 664-669, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23768946/&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;23768946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.04.009&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="23768946">Penisson-Besnier et al. (2013)</a> reported a 42-year-old French man who developed progressive proximal muscle weakness around 30 years of age. He had a history of easy bruising and inguinal hernias, but no joint hypermobility and only minimal skin hyperextensibility. EMG showed a myopathic pattern, imaging showed fatty infiltration of proximal muscle, and serum creatine kinase was increased. He had no cardiac symptoms, but echocardiography showed mildly hypokinetic left ventricle with reduced systolic function and minimal mitral regurgitation. Endocrine abnormalities were not reported. The muscle biopsy sample was soft and showed excessive internal myonuclei, focal sarcolemmal indentations that sometimes split the muscle cell, and increased connective tissue. There was also myofibrillar disorganization accompanied by focal disruption of the plasma membrane. Abnormal histologic features were restricted to a small number of myofibers reminiscent of myotendinous junctions within the muscle belly. Skin and muscle biopsies showed strong reduction in TNX content, and serum TNX was undetectable. These findings suggested that TNX deficiency leads to mislocalization of structures that transmit mechanical forces from muscle fibers to tendons. Molecular analysis identified compound heterozygous mutations in the TNXB gene (30-kb del, <a href="/entry/600985#0001">600985.0001</a> and R4072C, <a href="/entry/600985#0005">600985.0005</a>). <a href="#7" class="mim-tip-reference" title="Penisson-Besnier, I., Allamand, V., Beurrier, P., Martin, L., Schalkwijk, J., van Vlijmen-Willems, I., Gartioux, C., Malfait, F., Syx, D., Macchi, L., Marcorelles, P., Arbeille, B., Croue, A., De Paepe, A., Dubas, F. &lt;strong&gt;Compound heterozygous mutations of the TNXB gene cause primary myopathy.&lt;/strong&gt; Neuromusc. Disord. 23: 664-669, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23768946/&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;23768946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.04.009&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="23768946">Penisson-Besnier et al. (2013)</a> suggested that soft muscle may be a diagnostic clue for this disease entity, and emphasized the myopathic features apparent in this patient. <a href="#10" class="mim-tip-reference" title="Voermans, N. C., Gerrits, K., van Engelen, B. G., de Haan, A. &lt;strong&gt;Compound heterozygous mutations of the TNXB gene cause primary myopathy. (Letter)&lt;/strong&gt; Neuromusc. Disord. 24: 88-89, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24300784/&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;24300784&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.10.007&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="24300784">Voermans et al. (2014)</a> commented that in vivo studies of muscle strength in patients with TNX mutations have indicated that changes in the muscle matrix contribute to muscle weakness, thus confirming the report of <a href="#7" class="mim-tip-reference" title="Penisson-Besnier, I., Allamand, V., Beurrier, P., Martin, L., Schalkwijk, J., van Vlijmen-Willems, I., Gartioux, C., Malfait, F., Syx, D., Macchi, L., Marcorelles, P., Arbeille, B., Croue, A., De Paepe, A., Dubas, F. &lt;strong&gt;Compound heterozygous mutations of the TNXB gene cause primary myopathy.&lt;/strong&gt; Neuromusc. Disord. 23: 664-669, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23768946/&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;23768946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.04.009&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="23768946">Penisson-Besnier et al. (2013)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23768946+24300784" 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 25-year-old man with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (<a href="/entry/201910">201910</a>), associated with an Ehlers-Danlos syndrome phenotype, and in his unaffected father, <a href="#1" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D. &lt;strong&gt;Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 59 (suppl.): A16, 1996."None>Burch et al. (1996)</a> identified a 30-kb deletion resulting in loss of the CYP21 gene (<a href="/entry/603815">603815</a>) and creation of a hybrid gene between TNXB (<a href="/entry/600985">600985</a>) and the partially duplicated TNXB gene (called XA by them) with early termination of TNX translation (<a href="/entry/600985#0001">600985.0001</a>). The nature of the molecular lesion in the proband's second TNXB and CYP21 alleles was unknown. <a href="#1" class="mim-tip-reference" title="Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D. &lt;strong&gt;Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 59 (suppl.): A16, 1996."None>Burch et al. (1996)</a> concluded that the patient's Ehlers-Danlos syndrome phenotype was due to loss of TNXB and represented the first tenascin-related disease.</p><p>In 3 patients with an Ehlers-Danlos syndrome phenotype and tenascin-X deficiency, <a href="#9" class="mim-tip-reference" title="Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J. &lt;strong&gt;A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.&lt;/strong&gt; New Eng. J. Med. 345: 1167-1175, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11642233/&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;11642233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa002939&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="11642233">Schalkwijk et al. (2001)</a> identified homozygosity for a 30-kb deletion and 2 frameshift mutations in the TNXB gene, respectively (<a href="/entry/600985#0001">600985.0001</a>-<a href="/entry/600985#0003">600985.0003</a>). The patient who was homozygous for the 30-kb deletion also had CAH. In another 2 patients, only heterozygosity for the 30-kb deletion was detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11642233" 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 an 8-year-old girl with CAH due to 21-hydroxylase deficiency and an Ehlers-Danlos syndrome phenotype, <a href="#3" class="mim-tip-reference" title="Chen, W., Kim, M. S., Shanbhag, S., Arai, A., VanRyzin, C., McDonnell, N. B., Merke, D. P. &lt;strong&gt;The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects.&lt;/strong&gt; Am. J. Med. Genet. 149A: 2803-2808, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19921645/&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;19921645&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19921645[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33092&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="19921645">Chen et al. (2009)</a> identified a heterozygous 'In2G' mutation in the CYP21A2 gene, as well as a large deletion encompassing both CYP21A2 and the TNXB genes. Her mother and maternal grandfather, who exhibited hyperextensible joints, also carried the large deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19921645" 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="#13" class="mim-tip-reference" title="Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., Schalkwijk, J. &lt;strong&gt;Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 73: 214-217, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12865992/&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;12865992&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/376564&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="12865992">Zweers et al. (2003)</a> examined all 20 heterozygous members from 4 families with the recessive form of EDS due to homozygosity for mutations in the TNXB gene (<a href="/entry/600985#0001">600985.0001</a>-<a href="/entry/600985#0003">600985.0003</a>). Clinical examination revealed generalized joint hypermobility in 9 family members (45%). Skin hyperextensibility and easy bruising, frequently seen in individuals with complete TNX deficiency, were absent. A number of patients with haploinsufficiency had recurring joint dislocations and chronic joint pain, as seen in the hypermobility type of EDS and in benign joint hypermobility syndrome (BJHS; see <a href="/entry/130020">130020</a>). A striking finding was that none of the 6 males with TNXB haploinsufficiency fulfilled the clinical criteria for either the hypermobility type of EDS or BJHS, whereas 9 of 14 (64%) females were positive. This finding was in accordance with previous studies showing a female preponderance in joint hypermobility syndromes (<a href="#5" class="mim-tip-reference" title="Larsson, L. G., Baum, J., Mudholkar, G. S. &lt;strong&gt;Hypermobility: features and differential incidence between the sexes.&lt;/strong&gt; Arthritis Rheum. 30: 1426-1430, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3435571/&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;3435571&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/art.1780301216&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="3435571">Larsson et al., 1987</a>; <a href="#8" class="mim-tip-reference" title="Rikken-Bultman, D. G., Wellink, L., van Dongen, P. W. &lt;strong&gt;Hypermobility in two Dutch school populations.&lt;/strong&gt; Europ. J. Obstet. Gynec. Reprod. Biol. 73: 189-192, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9228503/&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;9228503&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0301-2115(97)02745-0&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="9228503">Rikken-Bultman et al., 1997</a>). <a href="#13" class="mim-tip-reference" title="Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., Schalkwijk, J. &lt;strong&gt;Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 73: 214-217, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12865992/&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;12865992&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/376564&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="12865992">Zweers et al. (2003)</a> measured TNX levels in an unselected cohort of 80 patients, approximately 90% of whom were female, who had been diagnosed with the hypermobility type of EDS by a medical specialist and who were recruited through a Dutch organization for EDS patients. Six of the patients had serum TNX levels more than 2.5 SD below the mean for unaffected individuals and showed hypermobile joints, often associated with joint subluxations and chronic musculoskeletal pain. They did not have skin hyperextensibility and lacked the easy bruising seen in patients with TNX deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9228503+12865992+3435571" 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 sporadic patient with hypermobility type EDS and normal TNX serum levels, <a href="#14" class="mim-tip-reference" title="Zweers, M. C., Dean, W. B., van Kuppevelt, T. H., Bristow, J., Schalkwijk, J. &lt;strong&gt;Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations.&lt;/strong&gt; Clin. Genet. 67: 330-334, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15733269/&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;15733269&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00401.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15733269">Zweers et al. (2005)</a> identified a heterozygous missense mutation in the TNXB gene (<a href="/entry/600985#0004">600985.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Zweers, M. C., Dean, W. B., van Kuppevelt, T. H., Bristow, J., Schalkwijk, J. &lt;strong&gt;Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations.&lt;/strong&gt; Clin. Genet. 67: 330-334, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15733269/&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;15733269&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00401.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15733269">Zweers et al. (2005)</a> found that the average length of the elastic fibers in the papillary dermis was significantly decreased in skin biopsies from 8 patients with TNX-haploinsufficient hypermobility type EDS compared to those from controls. Many elastic fibers had a moth-eaten appearance and irregular edges, or contained electron-dense inclusions. In contrast, there was no difference in elastic fiber length between patients with hypermobility type EDS without TNX mutations and controls. One EDS hypermobility patient with a heterozygous missense mutation in the TNXB gene (<a href="/entry/600985#0004">600985.0004</a>), but no decrease in serum TNX levels, had an increase in elastic fiber length compared to controls. <a href="#14" class="mim-tip-reference" title="Zweers, M. C., Dean, W. B., van Kuppevelt, T. H., Bristow, J., Schalkwijk, J. &lt;strong&gt;Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations.&lt;/strong&gt; Clin. Genet. 67: 330-334, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15733269/&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;15733269&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2005.00401.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15733269">Zweers et al. (2005)</a> concluded that elastic fiber abnormalities in hypermobility type EDS are specific for TNX-haploinsufficient individuals, and that TNX may play a role in regulating elastic fiber integrity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Voermans, N. C., Jenniskens, G. J., Hamel, B. C., Schalkwijk, J., Guicheney, P., van Engelen, B. G. &lt;strong&gt;Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 143A: 2215-2219, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17702048/&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;17702048&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31899&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="17702048">Voermans et al. (2007)</a> reported follow-up on one of the EDS patients reported by <a href="#9" class="mim-tip-reference" title="Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J. &lt;strong&gt;A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.&lt;/strong&gt; New Eng. J. Med. 345: 1167-1175, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11642233/&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;11642233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa002939&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="11642233">Schalkwijk et al. (2001)</a> who had a homozygous mutation in the TNXB gene (<a href="/entry/600985#0002">600985.0002</a>). In addition to classic clinical features of EDS, such as mild joint hypermobility, skin hyperextensibility, and easy bruising since childhood, she also had progressive generalized muscle weakness and distal contractures beginning at about age 40. She was unable to walk up stairs, had limited walking endurance of 1 hour, and had reduced gripping force. Needle biopsy of the quadriceps muscle did not show significant myopathic changes, but there was absence of immunostaining to tenascin XB and decreased endomysial staining for collagen VI (see, e.g., COL6A1; <a href="/entry/120220">120220</a>). <a href="#11" class="mim-tip-reference" title="Voermans, N. C., Jenniskens, G. J., Hamel, B. C., Schalkwijk, J., Guicheney, P., van Engelen, B. G. &lt;strong&gt;Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 143A: 2215-2219, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17702048/&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;17702048&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31899&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="17702048">Voermans et al. (2007)</a> noted that disruption of the TNXB gene, which is part of the extracellular matrix in skeletal muscle, results in decreased expression of type VI collagen. Thus, some patients with EDS due to tenascin deficiency may show myopathic features of collagen VI-related myopathies, such as Bethlem myopathy (BTHLM1; <a href="/entry/158810">158810</a>) and Ullrich congenital muscular dystrophy (UCMD1; <a href="/entry/254090">254090</a>). <a href="#4" class="mim-tip-reference" title="Kirschner, J., Hausser, I., Zou, Y., Schreiber, G., Christen, H.-J., Brown, S. C., Anton-Lamprecht, I., Muntoni, F., Hanefeld, F., Bonnemann, C. G. &lt;strong&gt;Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.&lt;/strong&gt; Am. J. Med. Genet. 132A: 296-301, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15690374/&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;15690374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30443&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="15690374">Kirschner et al. (2005)</a> had previously suggested an overlap in ultrastructural connective tissue abnormalities between patients with UCMD1 and EDS, namely, changes in collagen fibril morphology and increased ground substance. All 5 UCMD1 patients examined by <a href="#4" class="mim-tip-reference" title="Kirschner, J., Hausser, I., Zou, Y., Schreiber, G., Christen, H.-J., Brown, S. C., Anton-Lamprecht, I., Muntoni, F., Hanefeld, F., Bonnemann, C. G. &lt;strong&gt;Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.&lt;/strong&gt; Am. J. Med. Genet. 132A: 296-301, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15690374/&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;15690374&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30443&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="15690374">Kirschner et al. (2005)</a> had distal joint hypermobility, and some patients had abnormal scar formation, poor wound healing, and velvety skin texture as observed in EDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17702048+11642233+15690374" 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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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Burch1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D.
<strong>Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)</strong>
Am. J. Hum. Genet. 59 (suppl.): A16, 1996.
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Burch1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., Bristow, J.
<strong>Tenascin-X deficiency is associated with Ehlers-Danlos syndrome.</strong>
Nature Genet. 17: 104-108, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288108</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288108" 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/ng0997-104" target="_blank">Full Text</a>]
</p>
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<a id="3" class="mim-anchor"></a>
<a id="Chen2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chen, W., Kim, M. S., Shanbhag, S., Arai, A., VanRyzin, C., McDonnell, N. B., Merke, D. P.
<strong>The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects.</strong>
Am. J. Med. Genet. 149A: 2803-2808, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19921645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19921645</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19921645[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19921645" 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.33092" target="_blank">Full Text</a>]
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Kirschner2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kirschner, J., Hausser, I., Zou, Y., Schreiber, G., Christen, H.-J., Brown, S. C., Anton-Lamprecht, I., Muntoni, F., Hanefeld, F., Bonnemann, C. G.
<strong>Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.</strong>
Am. J. Med. Genet. 132A: 296-301, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15690374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15690374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15690374" 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.30443" target="_blank">Full Text</a>]
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<a id="Larsson1987" class="mim-anchor"></a>
<div class="">
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Larsson, L. G., Baum, J., Mudholkar, G. S.
<strong>Hypermobility: features and differential incidence between the sexes.</strong>
Arthritis Rheum. 30: 1426-1430, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3435571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3435571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3435571" 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/art.1780301216" target="_blank">Full Text</a>]
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<a id="Lindor2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lindor, N. M., Bristow, J.
<strong>Tenascin-X deficiency in autosomal recessive Ehlers-Danlos syndrome.</strong>
Am. J. Med. Genet. 135A: 75-80, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15793839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15793839</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15793839" 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.30671" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="Penisson-Besnier2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Penisson-Besnier, I., Allamand, V., Beurrier, P., Martin, L., Schalkwijk, J., van Vlijmen-Willems, I., Gartioux, C., Malfait, F., Syx, D., Macchi, L., Marcorelles, P., Arbeille, B., Croue, A., De Paepe, A., Dubas, F.
<strong>Compound heterozygous mutations of the TNXB gene cause primary myopathy.</strong>
Neuromusc. Disord. 23: 664-669, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23768946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23768946</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23768946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.nmd.2013.04.009" target="_blank">Full Text</a>]
</p>
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<a id="8" class="mim-anchor"></a>
<a id="Rikken-Bultman1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rikken-Bultman, D. G., Wellink, L., van Dongen, P. W.
<strong>Hypermobility in two Dutch school populations.</strong>
Europ. J. Obstet. Gynec. Reprod. Biol. 73: 189-192, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9228503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9228503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9228503" 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/s0301-2115(97)02745-0" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
<a id="Schalkwijk2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J.
<strong>A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.</strong>
New Eng. J. Med. 345: 1167-1175, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11642233/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11642233</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11642233" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMoa002939" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
<a id="Voermans2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Voermans, N. C., Gerrits, K., van Engelen, B. G., de Haan, A.
<strong>Compound heterozygous mutations of the TNXB gene cause primary myopathy. (Letter)</strong>
Neuromusc. Disord. 24: 88-89, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24300784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24300784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24300784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.nmd.2013.10.007" target="_blank">Full Text</a>]
</p>
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<a id="11" class="mim-anchor"></a>
<a id="Voermans2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Voermans, N. C., Jenniskens, G. J., Hamel, B. C., Schalkwijk, J., Guicheney, P., van Engelen, B. G.
<strong>Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. (Letter)</strong>
Am. J. Med. Genet. 143A: 2215-2219, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17702048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17702048</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17702048" 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.31899" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
<a id="Voermans2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Voermans, N. C., van Alfen, N., Pillen, S., Lammens, M., Schalkwijk, J., Zwarts, M. J., van Rooij, I. A., Hamel, B. C. J., van Engelen, B. G.
<strong>Neuromuscular involvement in various types of Ehlers-Danlos syndrome.</strong>
Ann. Neurol. 65: 687-697, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19557868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19557868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19557868" 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/ana.21643" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
<a id="Zweers2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., Schalkwijk, J.
<strong>Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. (Letter)</strong>
Am. J. Hum. Genet. 73: 214-217, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12865992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12865992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12865992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/376564" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
<a id="Zweers2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zweers, M. C., Dean, W. B., van Kuppevelt, T. H., Bristow, J., Schalkwijk, J.
<strong>Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations.</strong>
Clin. Genet. 67: 330-334, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15733269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15733269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15733269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.2005.00401.x" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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Cassandra L. Kniffin - updated : 8/26/2014
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Marla J. F. O'Neill - updated : 6/13/2012<br>Cassandra L. Kniffin - updated : 11/19/2009<br>Cassandra L. Kniffin - updated : 2/24/2009<br>Marla J. F. O'Neill - updated : 5/23/2005
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Victor A. McKusick : 10/22/2001
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carol : 06/26/2024
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carol : 03/01/2024<br>carol : 02/29/2024<br>carol : 05/29/2018<br>carol : 12/21/2017<br>carol : 07/20/2015<br>carol : 4/13/2015<br>carol : 8/27/2014<br>mcolton : 8/26/2014<br>ckniffin : 8/26/2014<br>alopez : 6/14/2012<br>terry : 6/13/2012<br>wwang : 2/17/2010<br>ckniffin : 11/19/2009<br>wwang : 3/4/2009<br>ckniffin : 2/24/2009<br>wwang : 6/8/2005<br>wwang : 6/2/2005<br>terry : 5/23/2005<br>mgross : 11/8/2001<br>mgross : 11/8/2001<br>mgross : 10/23/2001<br>mgross : 10/22/2001
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<h3>
<span class="mim-font">
<strong>#</strong> 606408
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<span class="mim-font">
EHLERS-DANLOS SYNDROME, CLASSIC-LIKE, 1; EDSCLL1
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<em>Alternative titles; symbols</em>
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EHLERS-DANLOS SYNDROME, CLASSIC-LIKE; EDSCLL<br />
EHLERS-DANLOS SYNDROME DUE TO TENASCIN-X DEFICIENCY<br />
EDS DUE TO TNX DEFICIENCY<br />
TNX DEFICIENCY
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<strong>SNOMEDCT:</strong> 778022009; &nbsp;
<strong>ORPHA:</strong> 230839; &nbsp;
<strong>DO:</strong> 0080731; &nbsp;
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<h4>
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<th>
Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<td>
<span class="mim-font">
6p21.33-p21.32
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<td>
<span class="mim-font">
Ehlers-Danlos syndrome, classic-like, 1
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<span class="mim-font">
606408
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Autosomal recessive
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3
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<span class="mim-font">
TNXB
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600985
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<span class="mim-font">
<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Ehlers-Danlos syndrome classic-like-1 (EDSCLL1) is caused by homozygous or compound heterozygous mutation in the tenascin-XB gene (TNXB; 600985) on chromosome 6p21.</p>
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<span class="mim-font">
<strong>Description</strong>
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<p>Ehlers-Danlos syndrome classic-like-1 (EDSCLL1) is a connective tissue disorder characterized by hyperextensible skin, hypermobile joints, and tissue fragility (Burch et al., 1996).</p><p><strong><em>Genetic Heterogeneity of Classic-Like Ehlers-Danlos Syndrome</em></strong></p><p>
EDSCLL2 (618000) is caused by mutation in the AEBP1 gene (602981) on chromosome 7p13, and EDSCLL3 (620865) is caused by mutation in the THBS2 gene (188061) on chromosome 6q27.</p><p>For a discussion of the classification of EDS, see 130000.</p>
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<h4>
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<strong>Clinical Features</strong>
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<p>Burch et al. (1996) reported a 25-year-old man with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (201910), associated with a classic Ehlers-Danlos syndrome (see 130000)-like phenotype, consisting of hyperextensible skin and joints, patellar chondromalacia, and easy bruising. In their full report, Burch et al. (1997) described atypical histologic findings that suggested a novel mechanism of disease in their proband: the most striking findings were abnormal elastin (130160) bodies beneath the dermal-epidermal junction, a diffuse increase in perivascular matrix, and uneven packing of the myelin sheaths of peripheral nerves. </p><p>To investigate the role of tenascins in EDS, Schalkwijk et al. (2001) screened serum samples from 151 patients with the classic, hypermobility, or vascular types of EDS for the presence of tenascin-X and tenascin-C (187380) by enzyme-linked immunosorbent assay. The same assays were done in 75 patients with psoriasis, 93 patients with rheumatoid arthritis, and 21 healthy persons. Absence of tenascin-X from the serum was found in 5 unrelated patients, all of whom had recessive EDS and 1 of whom also had CAH. All 5 tenascin-X-deficient patients and 3 clinically affected tenascin-X-deficient sibs had hyperelastic skin and hypermobile joints, fulfilling major diagnostic criteria for classic EDS. Minor diagnostic criteria supporting the diagnosis of classic EDS in these patients and their affected sibs included easy bruising in all, velvety skin in 7, joint pain in 2, and multiple subluxations in 3. Although the findings were similar to those of classic EDS, all tenascin-X-deficient patients lacked atrophic scars, a major diagnostic criteria for classic EDS. Delayed wound healing, which is also common in classic EDS, was not present in any of these patients, although it was noted in the tenascin-X-deficient patient reported by Burch et al. (1997). However, it was possible that treatment with glucocorticoids for congenital adrenal hyperplasia in that patient may have played a role in delayed wound healing. The tenascin-X-deficient patients reported by Schalkwijk et al. (2001) also had a range of additional clinical findings not typically associated with EDS, including congenital adrenal hyperplasia, spina bifida occulta, mitral valve prolapse, stroke, gastrointestinal bleeding, and premature arteriosclerosis. It was not clear whether these additional disorders were related to tenascin-X deficiency. None of the parents of the 5 patients with tenascin-X deficiency were related, and none of the 4 parents available for study had clinical signs of EDS. The authors identified mutations in the TNX gene in all 5 patients. </p><p>Lindor and Bristow (2005) described 2 unrelated patients with complete deficiency of tenascin-X who had marked skin hyperextensibility, easy bruising, and joint laxity. Unlike classic EDS patients, they did not have atrophic scarring or poor wound healing. Significant medical problems occurring in these individuals included severe diverticular intestinal disease with ruptured diverticula, pancolonic diverticulitis, and rectal prolapse, mitral valve prolapse requiring valve replacement, and obstructive airway disease. One patient had 3 daughters, presumed heterozygotes, who had minimal clinical expression of a tenascin-X deficiency phenotype and did not meet the diagnostic criteria for EDS. </p><p>Chen et al. (2009) reported an 8-year-old 46,XX girl, born with ambiguous genitalia, bicornuate uterus, single kidney, and grade III vesicoureteral reflux, who was found to have 21-hydroxylase deficiency. Examination at 8 years of age revealed bifid uvula, single palmar crease on the left hand, normal skin, mild arachnodactyly, and hyperextensible joints with a Beighton score of 8/9. Her mother, who had a history of urethral prolapse and hiatus hernia, also had hyperextensible joints (Beighton score, 7/9), and her maternal grandfather had hyperextensible thumbs, whereas her father had a Beighton score of 0/9. Cardiac MRI revealed a quadricuspid aortic valve in the proband; her mother had mild mitral valve prolapse and trace regurgitation by transthoracic echocardiogram. </p>
</span>
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<div>
<h4>
<span class="mim-font">
<strong>Other Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Voermans et al. (2009) performed a cross-sectional study on the presence of neuromuscular symptoms in 40 patients with various forms of EDS. Ten patients each were analyzed with classic EDS (see 130000), vascular EDS (130050), hypermobility EDS (130020), and TNX-deficient EDS. Overall, those with classic EDS and TNX-deficient EDS reported the most neuromuscular involvement, with muscle weakness, hypotonia, myalgia, easy fatigability, and intermittent paresthesias, although patients in all groups reported these features. Physical examination showed mild to moderate muscle weakness (85%) and reduction of vibration sense (60%) across all groups. Nerve conduction studies demonstrated axonal polyneuropathy in 5 (13%) of 39 patients. Needle electromyography showed myopathic EMG features in 9 (26%) and a mixed neurogenic-myopathic pattern in 21 (60%) of 35 patients. Muscle ultrasound showed increased echo intensity in 19 (48%) and atrophy in 20 (50%) of 40 patients. Mild myopathic features were seen on muscle biopsy of 5 (28%) of 18 patients. Patients with the hypermobility type EDS caused by TNXB haploinsufficiency were least affected. Voermans et al. (2009) postulated that abnormalities in muscle or nerve extracellular matrix may underlie these findings. </p><p>Penisson-Besnier et al. (2013) reported a 42-year-old French man who developed progressive proximal muscle weakness around 30 years of age. He had a history of easy bruising and inguinal hernias, but no joint hypermobility and only minimal skin hyperextensibility. EMG showed a myopathic pattern, imaging showed fatty infiltration of proximal muscle, and serum creatine kinase was increased. He had no cardiac symptoms, but echocardiography showed mildly hypokinetic left ventricle with reduced systolic function and minimal mitral regurgitation. Endocrine abnormalities were not reported. The muscle biopsy sample was soft and showed excessive internal myonuclei, focal sarcolemmal indentations that sometimes split the muscle cell, and increased connective tissue. There was also myofibrillar disorganization accompanied by focal disruption of the plasma membrane. Abnormal histologic features were restricted to a small number of myofibers reminiscent of myotendinous junctions within the muscle belly. Skin and muscle biopsies showed strong reduction in TNX content, and serum TNX was undetectable. These findings suggested that TNX deficiency leads to mislocalization of structures that transmit mechanical forces from muscle fibers to tendons. Molecular analysis identified compound heterozygous mutations in the TNXB gene (30-kb del, 600985.0001 and R4072C, 600985.0005). Penisson-Besnier et al. (2013) suggested that soft muscle may be a diagnostic clue for this disease entity, and emphasized the myopathic features apparent in this patient. Voermans et al. (2014) commented that in vivo studies of muscle strength in patients with TNX mutations have indicated that changes in the muscle matrix contribute to muscle weakness, thus confirming the report of Penisson-Besnier et al. (2013). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a 25-year-old man with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (201910), associated with an Ehlers-Danlos syndrome phenotype, and in his unaffected father, Burch et al. (1996) identified a 30-kb deletion resulting in loss of the CYP21 gene (603815) and creation of a hybrid gene between TNXB (600985) and the partially duplicated TNXB gene (called XA by them) with early termination of TNX translation (600985.0001). The nature of the molecular lesion in the proband's second TNXB and CYP21 alleles was unknown. Burch et al. (1996) concluded that the patient's Ehlers-Danlos syndrome phenotype was due to loss of TNXB and represented the first tenascin-related disease.</p><p>In 3 patients with an Ehlers-Danlos syndrome phenotype and tenascin-X deficiency, Schalkwijk et al. (2001) identified homozygosity for a 30-kb deletion and 2 frameshift mutations in the TNXB gene, respectively (600985.0001-600985.0003). The patient who was homozygous for the 30-kb deletion also had CAH. In another 2 patients, only heterozygosity for the 30-kb deletion was detected. </p><p>In an 8-year-old girl with CAH due to 21-hydroxylase deficiency and an Ehlers-Danlos syndrome phenotype, Chen et al. (2009) identified a heterozygous 'In2G' mutation in the CYP21A2 gene, as well as a large deletion encompassing both CYP21A2 and the TNXB genes. Her mother and maternal grandfather, who exhibited hyperextensible joints, also carried the large deletion. </p><p>Zweers et al. (2003) examined all 20 heterozygous members from 4 families with the recessive form of EDS due to homozygosity for mutations in the TNXB gene (600985.0001-600985.0003). Clinical examination revealed generalized joint hypermobility in 9 family members (45%). Skin hyperextensibility and easy bruising, frequently seen in individuals with complete TNX deficiency, were absent. A number of patients with haploinsufficiency had recurring joint dislocations and chronic joint pain, as seen in the hypermobility type of EDS and in benign joint hypermobility syndrome (BJHS; see 130020). A striking finding was that none of the 6 males with TNXB haploinsufficiency fulfilled the clinical criteria for either the hypermobility type of EDS or BJHS, whereas 9 of 14 (64%) females were positive. This finding was in accordance with previous studies showing a female preponderance in joint hypermobility syndromes (Larsson et al., 1987; Rikken-Bultman et al., 1997). Zweers et al. (2003) measured TNX levels in an unselected cohort of 80 patients, approximately 90% of whom were female, who had been diagnosed with the hypermobility type of EDS by a medical specialist and who were recruited through a Dutch organization for EDS patients. Six of the patients had serum TNX levels more than 2.5 SD below the mean for unaffected individuals and showed hypermobile joints, often associated with joint subluxations and chronic musculoskeletal pain. They did not have skin hyperextensibility and lacked the easy bruising seen in patients with TNX deficiency. </p><p>In a sporadic patient with hypermobility type EDS and normal TNX serum levels, Zweers et al. (2005) identified a heterozygous missense mutation in the TNXB gene (600985.0004). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Zweers et al. (2005) found that the average length of the elastic fibers in the papillary dermis was significantly decreased in skin biopsies from 8 patients with TNX-haploinsufficient hypermobility type EDS compared to those from controls. Many elastic fibers had a moth-eaten appearance and irregular edges, or contained electron-dense inclusions. In contrast, there was no difference in elastic fiber length between patients with hypermobility type EDS without TNX mutations and controls. One EDS hypermobility patient with a heterozygous missense mutation in the TNXB gene (600985.0004), but no decrease in serum TNX levels, had an increase in elastic fiber length compared to controls. Zweers et al. (2005) concluded that elastic fiber abnormalities in hypermobility type EDS are specific for TNX-haploinsufficient individuals, and that TNX may play a role in regulating elastic fiber integrity. </p><p>Voermans et al. (2007) reported follow-up on one of the EDS patients reported by Schalkwijk et al. (2001) who had a homozygous mutation in the TNXB gene (600985.0002). In addition to classic clinical features of EDS, such as mild joint hypermobility, skin hyperextensibility, and easy bruising since childhood, she also had progressive generalized muscle weakness and distal contractures beginning at about age 40. She was unable to walk up stairs, had limited walking endurance of 1 hour, and had reduced gripping force. Needle biopsy of the quadriceps muscle did not show significant myopathic changes, but there was absence of immunostaining to tenascin XB and decreased endomysial staining for collagen VI (see, e.g., COL6A1; 120220). Voermans et al. (2007) noted that disruption of the TNXB gene, which is part of the extracellular matrix in skeletal muscle, results in decreased expression of type VI collagen. Thus, some patients with EDS due to tenascin deficiency may show myopathic features of collagen VI-related myopathies, such as Bethlem myopathy (BTHLM1; 158810) and Ullrich congenital muscular dystrophy (UCMD1; 254090). Kirschner et al. (2005) had previously suggested an overlap in ultrastructural connective tissue abnormalities between patients with UCMD1 and EDS, namely, changes in collagen fibril morphology and increased ground substance. All 5 UCMD1 patients examined by Kirschner et al. (2005) had distal joint hypermobility, and some patients had abnormal scar formation, poor wound healing, and velvety skin texture as observed in EDS. </p>
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<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
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</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Burch, G. H., Gong, Y., Curry, C., Miller, W. L., Bristow, J. D.
<strong>Human tenascin-X deficiency causes an Ehlers-Danlos-like phenotype. (Abstract)</strong>
Am. J. Hum. Genet. 59 (suppl.): A16, 1996.
</p>
</li>
<li>
<p class="mim-text-font">
Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., Miller, W. L., Bristow, J.
<strong>Tenascin-X deficiency is associated with Ehlers-Danlos syndrome.</strong>
Nature Genet. 17: 104-108, 1997.
[PubMed: 9288108]
[Full Text: https://doi.org/10.1038/ng0997-104]
</p>
</li>
<li>
<p class="mim-text-font">
Chen, W., Kim, M. S., Shanbhag, S., Arai, A., VanRyzin, C., McDonnell, N. B., Merke, D. P.
<strong>The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects.</strong>
Am. J. Med. Genet. 149A: 2803-2808, 2009.
[PubMed: 19921645]
[Full Text: https://doi.org/10.1002/ajmg.a.33092]
</p>
</li>
<li>
<p class="mim-text-font">
Kirschner, J., Hausser, I., Zou, Y., Schreiber, G., Christen, H.-J., Brown, S. C., Anton-Lamprecht, I., Muntoni, F., Hanefeld, F., Bonnemann, C. G.
<strong>Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.</strong>
Am. J. Med. Genet. 132A: 296-301, 2005.
[PubMed: 15690374]
[Full Text: https://doi.org/10.1002/ajmg.a.30443]
</p>
</li>
<li>
<p class="mim-text-font">
Larsson, L. G., Baum, J., Mudholkar, G. S.
<strong>Hypermobility: features and differential incidence between the sexes.</strong>
Arthritis Rheum. 30: 1426-1430, 1987.
[PubMed: 3435571]
[Full Text: https://doi.org/10.1002/art.1780301216]
</p>
</li>
<li>
<p class="mim-text-font">
Lindor, N. M., Bristow, J.
<strong>Tenascin-X deficiency in autosomal recessive Ehlers-Danlos syndrome.</strong>
Am. J. Med. Genet. 135A: 75-80, 2005.
[PubMed: 15793839]
[Full Text: https://doi.org/10.1002/ajmg.a.30671]
</p>
</li>
<li>
<p class="mim-text-font">
Penisson-Besnier, I., Allamand, V., Beurrier, P., Martin, L., Schalkwijk, J., van Vlijmen-Willems, I., Gartioux, C., Malfait, F., Syx, D., Macchi, L., Marcorelles, P., Arbeille, B., Croue, A., De Paepe, A., Dubas, F.
<strong>Compound heterozygous mutations of the TNXB gene cause primary myopathy.</strong>
Neuromusc. Disord. 23: 664-669, 2013.
[PubMed: 23768946]
[Full Text: https://doi.org/10.1016/j.nmd.2013.04.009]
</p>
</li>
<li>
<p class="mim-text-font">
Rikken-Bultman, D. G., Wellink, L., van Dongen, P. W.
<strong>Hypermobility in two Dutch school populations.</strong>
Europ. J. Obstet. Gynec. Reprod. Biol. 73: 189-192, 1997.
[PubMed: 9228503]
[Full Text: https://doi.org/10.1016/s0301-2115(97)02745-0]
</p>
</li>
<li>
<p class="mim-text-font">
Schalkwijk, J., Zweers, M. C., Steijlen, P. M., Dean, W. B., Taylor, G., van Vlijmen, I. M., van Haren, B., Miller, W. L., Bristow, J.
<strong>A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.</strong>
New Eng. J. Med. 345: 1167-1175, 2001.
[PubMed: 11642233]
[Full Text: https://doi.org/10.1056/NEJMoa002939]
</p>
</li>
<li>
<p class="mim-text-font">
Voermans, N. C., Gerrits, K., van Engelen, B. G., de Haan, A.
<strong>Compound heterozygous mutations of the TNXB gene cause primary myopathy. (Letter)</strong>
Neuromusc. Disord. 24: 88-89, 2014.
[PubMed: 24300784]
[Full Text: https://doi.org/10.1016/j.nmd.2013.10.007]
</p>
</li>
<li>
<p class="mim-text-font">
Voermans, N. C., Jenniskens, G. J., Hamel, B. C., Schalkwijk, J., Guicheney, P., van Engelen, B. G.
<strong>Ehlers-Danlos syndrome due to tenascin-X deficiency: muscle weakness and contractures support overlap with collagen VI myopathies. (Letter)</strong>
Am. J. Med. Genet. 143A: 2215-2219, 2007.
[PubMed: 17702048]
[Full Text: https://doi.org/10.1002/ajmg.a.31899]
</p>
</li>
<li>
<p class="mim-text-font">
Voermans, N. C., van Alfen, N., Pillen, S., Lammens, M., Schalkwijk, J., Zwarts, M. J., van Rooij, I. A., Hamel, B. C. J., van Engelen, B. G.
<strong>Neuromuscular involvement in various types of Ehlers-Danlos syndrome.</strong>
Ann. Neurol. 65: 687-697, 2009.
[PubMed: 19557868]
[Full Text: https://doi.org/10.1002/ana.21643]
</p>
</li>
<li>
<p class="mim-text-font">
Zweers, M. C., Bristow, J., Steijlen, P. M., Dean, W. B., Hamel, B. C., Otero, M., Kucharekova, M., Boezeman, J. B., Schalkwijk, J.
<strong>Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. (Letter)</strong>
Am. J. Hum. Genet. 73: 214-217, 2003.
[PubMed: 12865992]
[Full Text: https://doi.org/10.1086/376564]
</p>
</li>
<li>
<p class="mim-text-font">
Zweers, M. C., Dean, W. B., van Kuppevelt, T. H., Bristow, J., Schalkwijk, J.
<strong>Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations.</strong>
Clin. Genet. 67: 330-334, 2005.
[PubMed: 15733269]
[Full Text: https://doi.org/10.1111/j.1399-0004.2005.00401.x]
</p>
</li>
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