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Entry
- #130050 - EHLERS-DANLOS SYNDROME, VASCULAR TYPE; EDSVASC
- OMIM
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<span class="h4">#130050</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/130050"><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="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#otherFeatures">Other Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=EHLERS-DANLOS SYNDROME, VASCULAR TYPE" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:14756" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/130050" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA000327/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:130050" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 17025000<br />
<strong>ICD10CM:</strong> Q79.63<br />
<strong>ORPHA:</strong> 286<br />
<strong>DO:</strong> 14756<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>
130050
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
EHLERS-DANLOS SYNDROME, VASCULAR TYPE; EDSVASC
</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, TYPE IV, AUTOSOMAL DOMINANT; EDS4<br />
EDS IV<br />
EHLERS-DANLOS SYNDROME, ARTERIAL TYPE<br />
EHLERS-DANLOS SYNDROME, ECCHYMOTIC TYPE<br />
EHLERS-DANLOS SYNDROME, SACK-BARABAS TYPE
</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/2/854?start=-3&limit=10&highlight=854">
2q32.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Ehlers-Danlos syndrome, vascular type
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/130050"> 130050 </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">
COL3A1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120180"> 120180 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/130050" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/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')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/130050" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/130050" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin lips <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301348000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301348000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000233</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000233</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Lobeless ears <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849364&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849364</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000387</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000387</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Keratoconus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65636009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65636009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H18.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H18.60</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H18.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H18.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/371.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">371.6</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/371.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">371.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022578</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000563" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000563</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000563" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000563</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pinched, thin nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851809&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851809</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Periodontal disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2556008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2556008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K05.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K05.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0031090&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0031090</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000704" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000704</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000704" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000704</a>]</span><br /> -
Early loss of teeth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42756003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42756003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232513&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232513</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006480" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006480</a>]</span><br /> -
Thin lips <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301348000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301348000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0578038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0578038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000233</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000233</a>]</span><br />
</span>
</div>
</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">
- Mitral valve prolapse <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>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Intracranial aneurysm <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128609009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128609009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007766&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007766</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004944</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004944</a>]</span><br /> -
Coronary artery aneurysm <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/50570003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">50570003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I25.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I25.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/414.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">414.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030882</a>]</span><br /> -
Aortic aneurysm <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/67362008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">67362008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I71.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I71.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/441.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">441.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0340629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340629</a>, <a href="https://bioportal.bioontology.org/search?q=C0003486&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003486</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004942</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004942</a>]</span><br /> -
Abdominal aortic aneurysm <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233985008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233985008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2926614&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2926614</a>, <a href="https://bioportal.bioontology.org/search?q=C0162871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162871</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005112" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005112</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005112" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005112</a>]</span><br /> -
Thoracic aneurysm <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/433068007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">433068007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162872&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162872</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012727" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012727</a>]</span><br /> -
Carotid cavernous sinus fistulae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302213007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302213007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238045&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238045</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031157" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031157</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Lung </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Spontaneous pneumothorax <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80423007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80423007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J93.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J93.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149781&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149781</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002108" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002108</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002108" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002108</a>]</span><br /> -
Hemoptysis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/6686005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">6686005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/66857006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">66857006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R04.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R04.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/786.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019079&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019079</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002105" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002105</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002105" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002105</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> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Inguinal hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396232000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396232000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K40.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">550</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019294</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Esophageal perforation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23387001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23387001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K22.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K22.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/530.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">530.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014860&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014860</a>]</span><br /> -
Stomach perforation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235674005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235674005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:6000383" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:6000383</a>]</span><br /> -
Spontaneous rupture of bowel or colon <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5829365&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5829365</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Female) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Uterine rupture associated with pregnancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851807&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851807</a>]</span><br /> -
Uterine prolapse <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/24976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">24976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N81.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N81.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/618.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">618.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042140&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042140</a>, <a href="https://bioportal.bioontology.org/search?q=C0553716&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0553716</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000139" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000139</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000139" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000139</a>]</span><br /> -
Cervical insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17382005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17382005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N88.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N88.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/622.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">622.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007871</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030009</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030009</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">
- Bladder prolapse <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0262393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0262393</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100645</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100645</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> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Congenital hip dislocation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52781008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52781008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48334007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48334007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q65.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q65.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551649&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551649</a>, <a href="https://bioportal.bioontology.org/search?q=C0019555&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019555</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001374" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001374</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001385" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001385</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001374" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001374</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypermobility of distal interphalangeal joints <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851811&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851811</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006201" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006201</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006201" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006201</a>]</span><br /> -
Acroosteolysis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63122002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63122002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27201004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27201004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0917990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0917990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009771</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009771</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Clubfoot <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br /> -
Acroosteolysis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63122002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63122002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27201004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27201004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0917990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0917990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009771</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009771" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009771</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">
- Fragile skin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247427007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247427007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241181&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241181</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001030</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 /> -
Cigarette-paper scars <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851828&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851828</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001073</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001073</a>]</span><br /> -
Atrophic skin over ears <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851813&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851813</a>]</span><br /> -
Prominent venous markings <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851814&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851814</a>]</span><br /> -
Absent-mild skin hyperextensibility <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851815&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851815</a>]</span><br /> -
Skin changes worse in areas of lower skin temperature <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851816</a>]</span><br /> -
Molluscoid pseudotumors <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844597&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844597</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000993</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000993</a>]</span><br /> -
Acrogeria (skin over hands and feet are thin and finely wrinkled) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851817</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/238872007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">238872007</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Alopecia of scalp <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298000004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298000004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0574769&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0574769</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002293</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Delivery </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Premature delivery because of cervical insufficiency or membrane fragility <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851808&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851808</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005267</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005267" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005267</a>]</span><br />
</span>
</div>
</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">
- Type III collagen defect <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851812&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851812</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">
- Death usually occurs before 5th decade<br /> -
Autosomal recessive inheritance has been reported in 1 family (as of April 2011)<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 collagen III, alpha-1 polypeptide gene (COL3A1, <a href="/entry/120180#0001">120180.0001</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/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/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/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>
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<p>A number sign (#) is used with this entry because vascular-type Ehlers-Danlos syndrome (EDSVASC) is caused by heterozygous mutation in the COL3A1 gene (<a href="/entry/120180">120180</a>) on chromosome 2q32.</p><p>Biallelic mutation in the COL3A1 gene causes polymicrogyria with or without vascular EDS (PMGVEDS; <a href="/entry/618343">618343</a>).</p>
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<p>The vascular type of Ehlers-Danlos syndrome is characterized by the major complications of arterial and bowel rupture, uterine rupture during pregnancy, and the clinical features of easy bruising, thin skin with visible veins, and characteristic facial features (summary by <a href="#23" class="mim-tip-reference" title="Leistritz, D. F., Pepin, M. G., Schwarze U., Byers, P. H. &lt;strong&gt;COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy.&lt;/strong&gt; Genet. Med. 13: 717-722, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21637106/&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;21637106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182180c89&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="21637106">Leistritz et al., 2011</a>). Joint hypermobility is largely limited to the digits, and skin hyperextensibility is minimal or absent (<a href="#27" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972."None>McKusick, 1972</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21637106" 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="#51" class="mim-tip-reference" title="Superti-Furga, A., Gugler, E., Gitzelmann, R., Steinmann, B. &lt;strong&gt;Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.&lt;/strong&gt; J. Biol. Chem. 263: 6226-6232, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2834369/&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;2834369&lt;/a&gt;]" pmid="2834369">Superti-Furga et al. (1988)</a> provided the first description of a mutation in the COL3A1 gene in type IV EDS. The proband was 22 years old; his father was affected with the same disorder and had died at age 34 years. He had been hospitalized for bleeding in the anterior abdominal wall and retroperitoneally following minor trauma. He went into cardiac arrest; open-chest cardiac massage resulted in avulsion of the heart from the superior vena cava with massive intrathoracic bleeding and death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2834369" 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>Type III procollagen is stored in dermal fibroblasts which show markedly dilated endoplasmic reticulum. <a href="#8" class="mim-tip-reference" title="Byers, P. H., Holbrook, K. A., McGillivray, B., MacLeod, P. M., Lowry, R. B. &lt;strong&gt;Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome.&lt;/strong&gt; Hum. Genet. 47: 141-150, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/437782/&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;437782&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00273196&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="437782">Byers et al. (1979)</a> emphasized the heterogeneity of EDS IV. Of 2 patients only 1 showed dilated endoplasmic reticulum. Probably a defect in type III collagen is a common feature. One of their patients showed keloid formation, a seemingly paradoxical feature that <a href="#28" class="mim-tip-reference" title="Mckusick, V. A. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Baltimore, Md. 1979."None>McKusick (1979)</a> also observed in this disorder. One patient had had spontaneous pneumothorax as well as spontaneous rupture of the bowel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=437782" 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="#40" class="mim-tip-reference" title="Pope, F. M., Nicholls, A. C., Jones, P. M., Wells, R. S., Lawrence, D. &lt;strong&gt;EDS IV (acrogeria): new autosomal dominant and recessive types.&lt;/strong&gt; J. Roy. Soc. Med. 73: 180-186, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7230200/&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;7230200&lt;/a&gt;]" pmid="7230200">Pope et al. (1980)</a> reported an apparent dominant form of EDS IV (in father and daughter). The acrogeric appearance of the skin of the hands was particularly striking in the 37-year-old father. A third patient (their patient 1) had severe acrogeric EDS IV. At age 7 she had been presented at the Section of Dermatology of the Royal Society of Medicine (<a href="#30" class="mim-tip-reference" title="Morris, D. &lt;strong&gt;Acrogeria.&lt;/strong&gt; J. Roy. Soc. Med. 50: 330-331, 1957."None>Morris, 1957</a>). At age 25 she suffered spontaneous rupture of the splenic artery and 3 years later had rupture of a left renal artery aneurysm. At age 29 she showed the typical facies and hand changes of acrogeria. The skin over the nose and ears was tight like that in scleroderma. Acroosteolysis was present. Chemical studies showed striking deficiency of type III collagen in all 3 cases. See <a href="/entry/120180#0015">120180.0015</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7230200" 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 18-year-old girl whom they considered to have EDS I, <a href="#11" class="mim-tip-reference" title="De Paepe, A., Nicholls, A., Narcisi, P., De Keyser, F., Quatacker, J., Van Staey, M., Matton, M., Pope, F. M. &lt;strong&gt;Ehlers-Danlos syndrome type I: a clinical and ultrastructural study of a family with reduced amounts of collagen type III.&lt;/strong&gt; Brit. J. Derm. 117: 89-97, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3651336/&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;3651336&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1365-2133.1987.tb04096.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="3651336">De Paepe et al. (1987)</a> found large, irregular collagen fibers by light microscopy of skin biopsies, with the same finding in the affected father. Electron microscopy showed variation in the diameter and shape of collagen fibrils as well as slight dilatation of the rough endoplasmic reticulum of fibroblasts in father and daughter. In both instances, the findings in the unaffected mother were normal. Synthesis of type III collagen was reduced to 50% of normal in the father and daughter. The patient had perhaps a greater tendency to bruising than do many EDS I patients. The abnormality in type III collagen suggested the diagnosis of EDS IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3651336" 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="Fox, R., Pope, F. M., Narcisi, P., Nicholls, A. C., Kendall, B. E., Hourihan, M. D., Compston, D. A. S. &lt;strong&gt;Spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 51: 984-986, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3204406/&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;3204406&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.51.7.984&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="3204406">Fox et al. (1988)</a> described a man who developed a spontaneous pulsating tinnitus in his left ear at the age of 20.5 years; he discovered accidentally that this noise could be stopped by firm pressure over the left side of the neck. Left-sided periorbital swelling, reddening of the conjunctiva, and ocular pain developed 6 months later, with left-sided pulsatile proptosis and a loud vascular bruit over the left orbit. Signs of EDS IV included thin nose and lips, hyperextensible joints, lax or thin skin with prominent venous markings, and small linear telangiectases on the trunk. There was a history of rectal bleeding attributed to multiple colonic diverticula. The patient was found to have a deficiency of type III collagen. The carotid-cavernous fistula was closed by means of a balloon catheter. <a href="#13" class="mim-tip-reference" title="Fox, R., Pope, F. M., Narcisi, P., Nicholls, A. C., Kendall, B. E., Hourihan, M. D., Compston, D. A. S. &lt;strong&gt;Spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 51: 984-986, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3204406/&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;3204406&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.51.7.984&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="3204406">Fox et al. (1988)</a> referred to 5 previously reported cases of the Ehlers-Danlos syndrome presenting as spontaneous carotid-cavernous fistula. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3204406" 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 group of 14 families, <a href="#45" class="mim-tip-reference" title="Rudd, N. L., Nimrod, C., Holbrook, K. A., Byers, P. H. &lt;strong&gt;Pregnancy complications in type IV Ehlers-Danlos syndrome.&lt;/strong&gt; Lancet 321: 50-53, 1983. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6129381/&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;6129381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(83)91577-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6129381">Rudd et al. (1983)</a> identified 20 women with EDS IV. The diagnosis was confirmed in at least 1 member of each family by demonstration of reduced production of type III collagen by dermal fibroblasts in vitro. Of the 20 women, 10 had been pregnant and 5 had died of pregnancy-related complications. The overall risk of death in each pregnancy was 25% in this series. Pregnancy-related complications included rupture of bowel, aorta, vena cava or uterus, vaginal laceration, and postpartum uterine hemorrhage. Nine of the families had 29 affected persons in an autosomal dominant pedigree pattern; the remaining 5 families had a single case. <a href="#41" class="mim-tip-reference" title="Pope, F. M., Nicholls, A. C. &lt;strong&gt;Pregnancy and Ehlers-Danlos syndrome type IV. (Letter)&lt;/strong&gt; Lancet 321: 249-250, 1983. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6130287/&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;6130287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(83)92631-4&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="6130287">Pope and Nicholls (1983)</a> took a less pessimistic view of pregnancy in EDS IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6129381+6130287" 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="Byard, R. W., Keeley, F. W., Smith, C. R. &lt;strong&gt;Type IV Ehlers-Danlos syndrome presenting as sudden infant death.&lt;/strong&gt; Am. J. Clin. Path. 93: 579-582, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2321591/&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;2321591&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/ajcp/93.4.579&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="2321591">Byard et al. (1990)</a> ascribed the 'sudden infant death syndrome' in a previously healthy 5-month-old female infant to type IV Ehlers-Danlos syndrome leading to spontaneous subarachnoid hemorrhage. The skin and aorta at postmortem showed a deficiency of type III collagen. There was no parental consanguinity and no family history of EDS, and both parents were aged 25. There were no gross features of EDS IV and the diagnosis was based exclusively on the finding that type III collagen in aorta and skin was reduced. <a href="#49" class="mim-tip-reference" title="Sherry, R. M., Fisch, A., Grey, D. P., Lubbock, C. A. &lt;strong&gt;Embolization of a hepatoportal fistula in a patient with Ehlers-Danlos syndrome and colon perforation.&lt;/strong&gt; Surgery 111: 475-478, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1557695/&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;1557695&lt;/a&gt;]" pmid="1557695">Sherry et al. (1992)</a> described a 16-year-old boy with EDS IV who developed a hepatoportal fistula 9 days after sigmoid colectomy and colostomy were performed for spontaneous rupture of the colon. The fistula was successfully occluded angiographically with a transcatheter coil <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1557695+2321591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 patients with inherited EDS IV, <a href="#53" class="mim-tip-reference" title="Superti-Furga, A., Saesseli, B., Steinmann, B., Bollinger, A. &lt;strong&gt;Microangiopathy in Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Int. J. Microcirc. Clin. Exp. 11: 241-247, 1992. Note: Erratum: Int. J. Microcirc. Clin. Exp. 11: 455 only, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1506129/&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;1506129&lt;/a&gt;]" pmid="1506129">Superti-Furga et al. (1992)</a> demonstrated evidence of microangiopathy of skin capillaries with microbleedings, microaneurysms, and increased transcapillary diffusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1506129" 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 series of 10 patients, <a href="#24" class="mim-tip-reference" title="Lewkonia, R. M., Pope, F. M. &lt;strong&gt;Joint contractures and acroosteolysis in Ehlers-Danlos syndrome type IV.&lt;/strong&gt; J. Rheum. 12: 140-144, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3981500/&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;3981500&lt;/a&gt;]" pmid="3981500">Lewkonia and Pope (1985)</a> found several with peripheral joint contractures and 3 who had acroosteolysis involving both fingers and toes. The simulation of chronic inflammatory joint disease was pointed out. <a href="#32" class="mim-tip-reference" title="Newton, T. H., Carpenter, M. E. &lt;strong&gt;Ehlers-Danlos syndrome with acro-osteolysis.&lt;/strong&gt; Brit. J. Radiol. 32: 739-743, 1959.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14426851/&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;14426851&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1259/0007-1285-32-383-739&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14426851">Newton and Carpenter (1959)</a> also reported acroosteolysis in EDS but it is not clear that the mother and daughter that they reported had type IV. They pointed out that the dislocation of the thumbs and other fingers may contribute to the simulation of rheumatoid arthritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3981500+14426851" 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="#59" class="mim-tip-reference" title="Yost, B. A., Vogelsang, J. P., Lie, J. T. &lt;strong&gt;Fatal hemoptysis in Ehlers-Danlos syndrome: old malady with a new curse.&lt;/strong&gt; Chest 107: 1465-1467, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7750352/&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;7750352&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1378/chest.107.5.1465&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="7750352">Yost et al. (1995)</a> described a 27-year-old man with EDS type IV who had recurrent and eventually fatal pulmonary hemorrhages. This had apparently not been previously described. <a href="#34" class="mim-tip-reference" title="North, K. N., Whiteman, D. A. H., Pepin, M. G., Byers, P. H. &lt;strong&gt;Cerebrovascular complications in Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Ann. Neurol. 38: 960-964, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8526472/&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;8526472&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410380620&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="8526472">North et al. (1995)</a> reviewed the cerebral vascular complications in 202 individuals with molecularly confirmed type IV Ehlers Danlos syndrome. Of these, 19 individuals had cerebral vascular complications which included intracranial aneurysms, spontaneous carotid cavernous sinus fistulas, and dissection of cervical arteries. The mean age at presentation of the cerebral vascular complication was 28.3 years ranging from 17 to 48. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7750352+8526472" 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="#38" class="mim-tip-reference" title="Phan, T. G., Sakulsaengprapha, A., Wilson, M., Wing, R. &lt;strong&gt;Ruptured internal mammary artery aneurysm presenting as massive spontaneous haemothorax in a patient with Ehlers-Danlos syndrome. (Letter)&lt;/strong&gt; Aust. New Zeal. J. Med. 28: 210-211, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9612531/&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;9612531&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1445-5994.1998.tb02972.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="9612531">Phan et al. (1998)</a> described a 39-year-old man with known EDS IV who presented with massive spontaneous hemothorax due to ruptured internal mammary artery aneurysm. He had first presented in his twenties with right renal infarction; 3 years later he underwent partial left nephrectomy for left renal infarction, and an aneurysm of the left renal artery was excised and the artery replaced. In addition to joint hypermobility, he had elastosis perforans serpiginosa. Emergency anterolateral thoracotomy for ligation of an abnormally fragile left internal mammary artery proximal to the aneurysm and drainage of an extensive hemothorax was accomplished successfully and postoperative recovery was uneventful. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9612531" 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>Commenting on the report of <a href="#37" class="mim-tip-reference" title="Pepin, M., Schwarze, U., Superti-Furga, A., Byers, P. H. &lt;strong&gt;Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type.&lt;/strong&gt; New Eng. J. Med. 342: 673-680, 2000. Note: Erratum: New Eng. J. Med. 344: 392 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10706896/&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;10706896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200003093421001&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="10706896">Pepin et al. (2000)</a>, <a href="#4" class="mim-tip-reference" title="Barabas, A. P. &lt;strong&gt;Ehlers-Danlos syndrome type IV. (Letter)&lt;/strong&gt; New Eng. J. Med. 343: 366 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10928897/&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;10928897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200008033430513&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="10928897">Barabas (2000)</a> stated that in his experience, teenage boys are at high risk for arterial rupture, which is often fatal. He suggested that this may be because during the prepubertal growth spurt the defective collagen is further weakened. He stated further that patients who undergo surgery are prone to arterial rupture in the postoperative period. <a href="#37" class="mim-tip-reference" title="Pepin, M., Schwarze, U., Superti-Furga, A., Byers, P. H. &lt;strong&gt;Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type.&lt;/strong&gt; New Eng. J. Med. 342: 673-680, 2000. Note: Erratum: New Eng. J. Med. 344: 392 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10706896/&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;10706896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200003093421001&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="10706896">Pepin et al. (2000)</a> had commented that preexisting aneurysms are only occasionally documented in patients who have arterial ruptures. <a href="#4" class="mim-tip-reference" title="Barabas, A. P. &lt;strong&gt;Ehlers-Danlos syndrome type IV. (Letter)&lt;/strong&gt; New Eng. J. Med. 343: 366 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10928897/&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;10928897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200008033430513&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="10928897">Barabas (2000)</a> suggested that this is because the patients with EDS type IV do not have true aneurysms. Aneurysms, if present, follow arterial tears and are walled-in hematomas or pseudoaneurysms. <a href="#4" class="mim-tip-reference" title="Barabas, A. P. &lt;strong&gt;Ehlers-Danlos syndrome type IV. (Letter)&lt;/strong&gt; New Eng. J. Med. 343: 366 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10928897/&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;10928897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200008033430513&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="10928897">Barabas (2000)</a> also drew attention to the danger of varicose vein surgery in unrecognized cases of EDS type IV, since the extreme fragility of all blood vessels can lead to loss of a limb or even loss of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10928897+10706896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Kroes, H. Y., Pals, G., van Essen, A. J. &lt;strong&gt;Ehlers-Danlos syndrome type IV: unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile.&lt;/strong&gt; Clin. Genet. 63: 224-227, 2003. Note: Erratum: Clin. Genet. 64: 375 only, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12694234/&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;12694234&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1034/j.1399-0004.2003.00047.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="12694234">Kroes et al. (2003)</a> described a mother and son with EDS type IV and unusual congenital anomalies. The mother had amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephalus; the son had esophageal atresia and hydrocephalus. The family was also anomalous in that protein analysis of collagen III in cultured fibroblasts of the mother showed no abnormalities; however, DNA analysis of the COL3A1 gene revealed a pathogenic mutation (<a href="/entry/120180#0031">120180.0031</a>) in both the mother and the son. The relationship between the COL3A1 mutation and the congenital anomalies was not clear. The experience emphasized the importance of performing both collagen protein analysis and DNA analysis of COL3A1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12694234" 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 16 patients with EDS type IV and 16 age-, gender-, and blood pressure-matched controls, <a href="#5" class="mim-tip-reference" title="Boutouyrie, P., Germain, D. P., Fiessinger, J.-N., Laloux, B., Perdu, J., Laurent, S. &lt;strong&gt;Increased carotid wall stress in vascular Ehlers-Danlos syndrome&lt;/strong&gt; Circulation 109: 1530-1535, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15007000/&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;15007000&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1161/01.CIR.0000121741.50315.C2&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="15007000">Boutouyrie et al. (2004)</a> measured circumferential wall stress in an elastic (common carotid) and a muscular (radial) artery. In the carotid artery, steady circumferential wall stress was 43% higher in EDS patients than in controls, pulsatile circumferential wall stress was 22% higher, and carotid intima-media thickness was 32% lower (p less than 0.001 for all findings). Carotid internal diameter and radial artery parameters were not significantly different between the 2 groups. <a href="#5" class="mim-tip-reference" title="Boutouyrie, P., Germain, D. P., Fiessinger, J.-N., Laloux, B., Perdu, J., Laurent, S. &lt;strong&gt;Increased carotid wall stress in vascular Ehlers-Danlos syndrome&lt;/strong&gt; Circulation 109: 1530-1535, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15007000/&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;15007000&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1161/01.CIR.0000121741.50315.C2&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="15007000">Boutouyrie et al. (2004)</a> concluded that the abnormally low intima-media thickness of elastic arteries in EDS IV patients generates higher wall stress, which may increase the risk of arterial dissection and rupture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15007000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Germain, D. P., Herrera-Guzman, Y. &lt;strong&gt;Vascular Ehlers-Danlos syndrome.&lt;/strong&gt; Ann. Genet. 47: 1-9, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15127738/&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;15127738&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.anngen.2003.07.002&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="15127738">Germain and Herrera-Guzman (2004)</a> provided an extensive review of EDS IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15127738" 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="#31" class="mim-tip-reference" title="Murray, M. L., Pepin, M., Peterson, S., Byers, P. H. &lt;strong&gt;Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos syndrome.&lt;/strong&gt; Genet. Med. 16: 874-880, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922461/&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;24922461&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.53&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="24922461">Murray et al. (2014)</a> reported pregnancy-related complications and deaths in women with vascular Ehlers-Danlos syndrome. Pregnancy-related deaths occurred in 30 (5.3%) of 565 deliveries. There was no difference in Kaplan-Meier survival curves between parous and nulliparous women with vascular EDS. Interviews with 39 women indicated that 46% of deliveries were uncomplicated. The most common complications were third- or fourth-degree lacerations in 20% and preterm delivery in 19%. Life-threatening complications occurred in 14.5% of deliveries and included arterial dissection/rupture (9.2%), uterine rupture (2.6%), and surgical complications (2.6%). There were 5 maternal deaths (6.5%) in 76 deliveries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24922461" 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="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a> reviewed clinical records from 1,231 individuals with vascular EDS and found median survival of 51 years; this was influenced by gender (lower in men) and by the type of mutation. Aortic aneurysm, dissection, or rupture was the leading single vascular complication (22%) recorded, leading to death in 68% of patients. Coronary artery aneurysm, dissection, or rupture was described in 25 individuals (9 males and 16 females); the mean age of the event was 30.8 years (25.0 for males and 33.5 for females). Twenty-seven carotid cavernous sinus fistulae were described (22 in females, 5 in males), with mean age of event at 30.9 years. Lethal cerebral vascular accidents without detailed description were reported in 15 of the 38 individuals who suffered 'intracranial' events. There were 181 bowel perforations described in this cohort: 117 (65%) colon or bowel perforations; 52 (29%) sigmoid colon; 8 (4%) small bowel; and 4 (2%) esophagus or stomach. Four birth defects occurred with a significantly greater frequency than the currently estimated prevalence in the United States (p less than 0.01, Z-test). Clubfoot or unilateral or bilateral defect was recorded in 8% of study subjects. Congenital hip dislocation, limb deficiency, and amniotic band were recorded in roughly 1% of patients, which was well above the estimated US prevalence. <a href="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a> identified 295 individuals less than 18 years of age with vascular EDS; 174 (60%) were tested in the presence of a positive family history. Of those 174, 13% had experienced a major complication, and the mean age of testing was 8 years. Among individuals less than 18 years of age with a negative family history, the proportion ascertained on the basis of a major complication was greater (52%), and the age of testing was older (mean of 11.5 years). In the absence of a positive family history or a major complication, the features most commonly identified as the reason for testing were easy bruising, thin skin, and joint hypermobility, in combination with clubfoot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24922459" 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 studies of cell strains from 8 cases of EDS IV, <a href="#54" class="mim-tip-reference" title="Superti-Furga, A., Steinmann, B., Ramirez, F., Byers, P. H. &lt;strong&gt;Molecular defects of type III procollagen in Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Hum. Genet. 82: 104-108, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2722184/&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;2722184&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00284038&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="2722184">Superti-Furga et al. (1989)</a> found evidence in 7 of structural defects in half of the type III procollagen chains synthesized, such as deletions or amino acid substitutions, which cause delayed formation and destabilization of the collagen triple helix and, as a consequence, reduced secretion of the molecule. In 3 of the families the inheritance was demonstrably autosomal dominant. One patient who had been thought to have a recessively inherited form of EDS IV (<a href="#39" class="mim-tip-reference" title="Pope, F. M., Martin, G. R., McKusick, V. A. &lt;strong&gt;Inheritance of Ehlers-Danlos type IV syndrome.&lt;/strong&gt; J. Med. Genet. 14: 200-204, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/881711/&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;881711&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.14.3.200&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="881711">Pope et al., 1977</a>) was found to have normal mRNA levels in the cells and secretion of a small amount of normal type III collagen, compatible with heterozygosity for a mutation in the COL3A1 gene. Because type III procollagen is a homotrimer, a structural defect in one-half of newly synthesized pro-alpha-1(III) chains will result in assembly of one-eighth normal and seven-eighths abnormal procollagen molecules. The mutant procollagen molecules described by <a href="#55" class="mim-tip-reference" title="Superti-Furga, A., Steinmann, B. &lt;strong&gt;Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 150: 140-147, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3337712/&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;3337712&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0006-291x(88)90497-4&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="3337712">Superti-Furga and Steinmann (1988)</a> and Superti-Furga et al. (<a href="#52" class="mim-tip-reference" title="Superti-Furga, A., Royce, P. M., Gugler, E., Gitzelmann, R., Steinmann, B. &lt;strong&gt;A structural defect of type III collagen causing Ehlers-Danlos syndrome type IV. (Abstract)&lt;/strong&gt; Pediat. Res. 20: 1043, 1986."None>1986</a>, <a href="#51" class="mim-tip-reference" title="Superti-Furga, A., Gugler, E., Gitzelmann, R., Steinmann, B. &lt;strong&gt;Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.&lt;/strong&gt; J. Biol. Chem. 263: 6226-6232, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2834369/&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;2834369&lt;/a&gt;]" pmid="2834369">1988</a>) had decreased thermal stability, were less efficiently secreted, and were not normally processed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2722184+881711+2834369+3337712" 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="#50" class="mim-tip-reference" title="Steinmann, B., Superti-Furga, A., Joller-Jemelka, H. I., Cetta, G., Byers, P. H. &lt;strong&gt;Ehlers-Danlos syndrome type IV--a subset of patients distinguished by low serum levels of the amino-terminal propeptide of type III procollagen.&lt;/strong&gt; Am. J. Med. Genet. 34: 68-71, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2816989/&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;2816989&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320340113&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="2816989">Steinmann et al. (1989)</a> found that serum levels of procollagen type III aminopropeptide, a peptide released during conversion of type III procollagen to collagen, were abnormally low in 6 of 10 patients with EDS IV and low-normal in 4 other such patients. The serum levels correlated with the amount of type III procollagen secreted by the patients' cultured fibroblasts. <a href="#7" class="mim-tip-reference" title="Byers, P. H., Barsh, G. S., Holbrook, K. A. &lt;strong&gt;Molecular mechanisms of connective tissue abnormalities in the Ehlers-Danlos syndrome.&lt;/strong&gt; Coll. Relat. Res. 1: 475-489, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6125299/&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;6125299&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0174-173x(81)80030-1&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="6125299">Byers et al. (1981)</a> reviewed the state of knowledge about collagen defects in the several forms of the Ehlers-Danlos syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6125299+2816989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="otherFeatures" class="mim-anchor"></a>
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<p><a href="#8" class="mim-tip-reference" title="Byers, P. H., Holbrook, K. A., McGillivray, B., MacLeod, P. M., Lowry, R. B. &lt;strong&gt;Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome.&lt;/strong&gt; Hum. Genet. 47: 141-150, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/437782/&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;437782&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00273196&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="437782">Byers et al. (1979)</a> demonstrated a predominance of collagen fibers of small diameter in EDS IV with or without intracellular accumulation. Dilation of the endoplasmic reticulum is a normal finding in plasma cells, where immunoglobin is the storage material. It is an abnormal finding in hepatocytes in alpha-1-antitrypsin deficiency (<a href="/entry/613490">613490</a>), and in chondrocytes in pseudoachondroplasia (<a href="/entry/177170">177170</a>) (<a href="#26" class="mim-tip-reference" title="Maynard, J. A., Cooper, R. R., Ponseti, I. V. &lt;strong&gt;A unique rough surfaced endoplasmic reticulum inclusion in pseudoachondroplasia.&lt;/strong&gt; Lab. Invest. 26: 40-46, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4333078/&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;4333078&lt;/a&gt;]" pmid="4333078">Maynard et al., 1972</a>) and metaphyseal dysostosis, presumably of the Murk Jansen type (<a href="/entry/156400">156400</a>) (<a href="#10" class="mim-tip-reference" title="Cooper, R. R., Pedrini-Mille, A., Ponseti, I. V. &lt;strong&gt;Metaphyseal dysostosis: a rough surfaced endoplasmic reticulum storage defect.&lt;/strong&gt; Lab. Invest. 28: 119-125, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4265987/&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;4265987&lt;/a&gt;]" pmid="4265987">Cooper et al., 1973</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4265987+4333078+437782" 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>Temperature effects on the rate of synthesis and/or the stability of the collagen would account well for the acrogeric appearance of the hands and face with pinched nose and atrophic skin over the ears that is displayed by some patients (see fig. 6-10, p. 311, in <a href="#27" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972."None>McKusick, 1972</a>).</p><p><a href="#56" class="mim-tip-reference" title="Superti-Furga, A., Steinmann, B. &lt;strong&gt;Ehlers-Danlos syndrome type IV: another temperature-dependent skin disorder? (Letter)&lt;/strong&gt; J. Am. Acad. Derm. 21: 323, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2768588/&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;2768588&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0190-9622(89)70192-4&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="2768588">Superti-Furga and Steinmann (1989)</a> expanded the possibility that this disorder is a temperature-dependent condition and that the atrophic changes of the skin on the hands, ears, and nose can be so explained. The suggestion was based on their demonstration that the structurally abnormal type III procollagen, which is retained within fibroblasts at 37 degrees C, can be secreted sufficiently when the temperature is lowered to 32 degrees C or below. They suggested that the presence of defective molecules in the extracellular space leads to disorganization of collagen fibrils and therefore to more pronounced skin changes in the areas of lower skin temperature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2768588" 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="#58" 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 among 40 patients with various forms of EDS. Ten patients each were analyzed with classic type I EDS (<a href="/entry/130000">130000</a>), vascular EDS, hypermobility EDS (<a href="/entry/130020">130020</a>), and TNX-deficient EDS (<a href="/entry/606408">606408</a>). 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="#58" 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="#42" class="mim-tip-reference" title="Prontera, P., Belcastro, V., Calabresi, P., Donti, E. &lt;strong&gt;Myostatin depletion: a therapy for Ehlers-Danlos syndrome?&lt;/strong&gt; Ann. Neurol. 67: 147-148, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20186851/&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;20186851&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21828&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="20186851">Prontera et al. (2010)</a> reported a 42-year old Italian man with a complex EDS phenotype caused by a 13.7-Mb de novo heterozygous deletion of chromosome 2q23.3-q31.2 resulting in deletion of the COL3A1, COL5A2 (<a href="/entry/120190">120190</a>), and myostatin (MSTN; <a href="/entry/601788">601788</a>) genes. Loss of function mutations in COL3A1 and COL5A2 cause EDS types IV and I, respectively. Haploinsufficiency for MSTN results in overgrowth of skeletal muscle. Due to the monosomy for MSTN, the patient had 'an exceptional constitutional muscular mass,' without muscle weakness, myalgia, or easy fatigability. He also had no generalized joint hypomobility or recurrent joint dislocation; symptoms of EDS were limited to recurrent inguinal hernias and mild mitral valve prolapse. <a href="#42" class="mim-tip-reference" title="Prontera, P., Belcastro, V., Calabresi, P., Donti, E. &lt;strong&gt;Myostatin depletion: a therapy for Ehlers-Danlos syndrome?&lt;/strong&gt; Ann. Neurol. 67: 147-148, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20186851/&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;20186851&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21828&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="20186851">Prontera et al. (2010)</a> hypothesized that haploinsufficiency for the MSTN allele exerted a protective effect again EDS clinical manifestations in this patient. The findings also indicated that there is direct involvement of muscle damage in EDS and that care of muscle function in these patients may be beneficial. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186851" 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="#2" class="mim-tip-reference" title="Barabas, A. P. &lt;strong&gt;Vascular complications in the Ehlers-Danlos syndrome, with special reference to the &#x27;arterial type&#x27; or Sack&#x27;s syndrome.&lt;/strong&gt; J. Cardiovasc. Surg. (Torino) 13: 160-167, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5034837/&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;5034837&lt;/a&gt;]" pmid="5034837">Barabas (1972)</a> reported a family in which the mother and a 16-year-old brother died of aortic rupture and the proband had frequent hematomata and at least one intraperitoneal bleed. The transmission pattern was consistent with autosomal dominant inheritance. <a href="#3" class="mim-tip-reference" title="Barabas, A. P. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Bury St. Edmunds, England 2/26/1975."None>Barabas (1975)</a>, whose name along with Sack's is applied eponymically to this condition, later reported 3 sporadic and 2 familial cases. In 1 family the mother was affected and died of a tear in her abdominal aorta following her fourth pregnancy. The eldest boy died at the age of 16 of similar complications. A daughter 'has survived several major arterial catastrophes.' The inheritance appeared to be dominant in the other family also. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5034837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Byers, P. H. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Seattle, Washington 6/3/1980."None>Byers (1980)</a> identified 4 autosomal dominant families. In 1 kindred a father and his son and daughter were affected; the father and daughter died of catastrophes. Several members of the next generation are also affected. Two autosomal dominant forms may exist: one with and one without dilated endoplasmic reticulum. These may be allelic disorders, however; in AAT deficiency, similar forms with and without accumulation are observed.</p><p><a href="#54" class="mim-tip-reference" title="Superti-Furga, A., Steinmann, B., Ramirez, F., Byers, P. H. &lt;strong&gt;Molecular defects of type III procollagen in Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Hum. Genet. 82: 104-108, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2722184/&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;2722184&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00284038&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="2722184">Superti-Furga et al. (1989)</a> supported the view that the great majority of cases of EDS IV have autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2722184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="mapping" class="mim-anchor"></a>
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<strong>Mapping</strong>
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<p>Although the lod score (1.8 at 0.0 recombination) did not achieve the level of 3.0, <a href="#47" class="mim-tip-reference" title="Schwartz, R. C., Byers, P. H., Chu, M.-L., Weil, D., Ramirez, F., Tsipouras, P. &lt;strong&gt;Ehlers-Danlos syndrome type IV (EDS IV): genetic linkage to the pro-alpha-1(III) collagen gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A173, 1985."None>Schwartz et al. (1985)</a> could conclude from linkage studies with a COL3A1 probe that the collagen III gene is probably mutant in a 3-generation family with EDS IV. <a href="#57" class="mim-tip-reference" title="Tsipouras, P., Byers, P. H., Schwartz, R. C., Chu, M.-L., Weil, D., Pepe, G., Cassidy, S. B., Ramirez, F. &lt;strong&gt;Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen.&lt;/strong&gt; Hum. Genet. 74: 41-46, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2875936/&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;2875936&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00278783&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="2875936">Tsipouras et al. (1986)</a> reported further on the study presented in abstract by <a href="#47" class="mim-tip-reference" title="Schwartz, R. C., Byers, P. H., Chu, M.-L., Weil, D., Ramirez, F., Tsipouras, P. &lt;strong&gt;Ehlers-Danlos syndrome type IV (EDS IV): genetic linkage to the pro-alpha-1(III) collagen gene. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A173, 1985."None>Schwartz et al. (1985)</a>. Findings in 2 kindreds indicated linkage. The lod score was 2.10 at theta = 0.00 in their family A and 0.30 at theta = 0.00 in their family B. Biochemically, the defect was somewhat different in the 2 families. Linkage analysis in a large Belgian family segregating autosomal dominant Ehlers-Danlos syndrome type IV was consistent with linkage of the EDS IV phenotype to the COL3A1 locus. However, no abnormality was detected in the type III collagen produced by the patients, and immunofluorescent and tissue analysis demonstrated significant amounts of type III collagen in the tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2875936" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="De Paepe, A., Van den Bossche, H., Mortier, G., Matton, M. &lt;strong&gt;Les syndromes d&#x27;Ehlers-Danlos et de Marfan chez le jeune enfant.&lt;/strong&gt; J. Genet. Hum. 36: 247-253, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3411305/&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;3411305&lt;/a&gt;]" pmid="3411305">De Paepe et al. (1988)</a> described a kindred with EDS IV in 11 members of 3 generations with numerous examples of male-to-male transmission. Deficiency in the synthesis of type III collagen was identified in cultured skin fibroblasts. By use of a RFLP associated with the COL3A1 gene, tight linkage was found between the gene and the disease; no definite recombinant was identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3411305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p><a href="#55" class="mim-tip-reference" title="Superti-Furga, A., Steinmann, B. &lt;strong&gt;Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 150: 140-147, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3337712/&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;3337712&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0006-291x(88)90497-4&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="3337712">Superti-Furga and Steinmann (1988)</a> and Superti-Furga et al. (<a href="#52" class="mim-tip-reference" title="Superti-Furga, A., Royce, P. M., Gugler, E., Gitzelmann, R., Steinmann, B. &lt;strong&gt;A structural defect of type III collagen causing Ehlers-Danlos syndrome type IV. (Abstract)&lt;/strong&gt; Pediat. Res. 20: 1043, 1986."None>1986</a>, <a href="#51" class="mim-tip-reference" title="Superti-Furga, A., Gugler, E., Gitzelmann, R., Steinmann, B. &lt;strong&gt;Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.&lt;/strong&gt; J. Biol. Chem. 263: 6226-6232, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2834369/&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;2834369&lt;/a&gt;]" pmid="2834369">1988</a>) showed that a patient with severe, dominantly inherited EDS IV had a deletion of 3.3 kb in the triple-helical coding domain of 1 of the 2 genes for the pro-alpha-chains of type III collagen. His cultured skin fibroblasts contained equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesized both normal and shortened procollagen chains. In procollagen molecules containing 1 or more shortened chains, a triple helix was formed with a length of only about 780 amino acids. The mutant procollagen molecules had decreased thermal stability, were less efficiently secreted, and were not normally processed. This was the first description of the molecular lesion in the COL3A1 gene in a case of EDS type IV. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2834369+3337712" 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 affected members of the family reported by <a href="#13" class="mim-tip-reference" title="Fox, R., Pope, F. M., Narcisi, P., Nicholls, A. C., Kendall, B. E., Hourihan, M. D., Compston, D. A. S. &lt;strong&gt;Spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 51: 984-986, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3204406/&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;3204406&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.51.7.984&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="3204406">Fox et al. (1988)</a>, <a href="#43" class="mim-tip-reference" title="Richards, A. J., Ward, P. N., Narcisi, P., Nicholls, A. C., Lloyd, J. C., Pope, F. M. &lt;strong&gt;A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV: an unaffected family member is mosaic for the mutation.&lt;/strong&gt; Hum. Genet. 89: 414-418, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1352273/&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;1352273&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194313&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="1352273">Richards et al. (1992)</a> described a gly847-to-glu mutation of the COL3A1 gene (<a href="/entry/120180#0014">120180.0014</a>). This family included an unaffected member who was mosaic for the mutation. <a href="#20" class="mim-tip-reference" title="Kontusaari, S., Tromp, G., Kuivaniemi, H., Stolle, C., Pope, F. M., Prockop, D. J. &lt;strong&gt;Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother.&lt;/strong&gt; Am. J. Hum. Genet. 51: 497-507, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1496983/&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;1496983&lt;/a&gt;]" pmid="1496983">Kontusaari et al. (1992)</a> described mosaicism for a mutation in the COL3A1 gene in the asymptomatic mother of a patient with EDS type IV (<a href="/entry/120180#0015">120180.0015</a>). <a href="#29" class="mim-tip-reference" title="Milewicz, D. M., Witz, A. M., Smith, A. C. M., Manchester, D. K., Waldstein, G., Byers, P. H. &lt;strong&gt;Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring.&lt;/strong&gt; Am. J. Hum. Genet. 53: 62-70, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8317500/&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;8317500&lt;/a&gt;]" pmid="8317500">Milewicz et al. (1993)</a> found heterozygosity for a 2-kb deletion in the COL3A1 gene in a severely affected teenaged girl whose asymptomatic father was mosaic for the same deletion. <a href="#29" class="mim-tip-reference" title="Milewicz, D. M., Witz, A. M., Smith, A. C. M., Manchester, D. K., Waldstein, G., Byers, P. H. &lt;strong&gt;Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring.&lt;/strong&gt; Am. J. Hum. Genet. 53: 62-70, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8317500/&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;8317500&lt;/a&gt;]" pmid="8317500">Milewicz et al. (1993)</a> gave a useful summary of the numerous autosomal dominant or X-linked recessive disorders in which this phenomenon has been observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3204406+1496983+1352273+8317500" 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="#15" class="mim-tip-reference" title="Gilchrist, D., Schwarze, U., Shields, K., MacLaren, L., Bridge, P. J., Byers, P. H. &lt;strong&gt;Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives.&lt;/strong&gt; Am. J. Med. Genet. 82: 305-311, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10051163/&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;10051163&lt;/a&gt;]" pmid="10051163">Gilchrist et al. (1999)</a> identified a gly571-to-ser substitution in the triple helical domain of the products of one COL3A1 allele (<a href="/entry/120180#0026">120180.0026</a>) in a large family with a milder phenotype than that typically associated with EDS IV. Clinical presentation in some of the affected members occurred at a later age than usual. Longevity was longer than that seen in many families, and there was less pregnancy-associated morbidity or mortality than that found in some families. The authors suggested that some clinical aspects of EDS IV may be related to the nature of the mutation and its effect on the behavior of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051163" 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="#35" class="mim-tip-reference" title="Palmeri, S., Mari, F., Meloni, I., Malandrini, A., Ariani, F., Villanova, M., Pompilio, A., Schwarze, U., Byers, P. H., Renieri, A. &lt;strong&gt;Neurological presentation of Ehlers-Danlos syndrome type IV in a family with parental mosaicism.&lt;/strong&gt; Clin. Genet. 63: 510-515, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12786757/&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;12786757&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1034/j.1399-0004.2003.00075.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="12786757">Palmeri et al. (2003)</a> characterized 7 members of a family with EDS IV. The index patient, a young woman with an acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon retraction, finger flexion contractures, and seizures. The mother had similar features and had experienced an ischemic stroke at the age of 43 years. A gly883-to-val mutation in the COL3A1 gene (<a href="/entry/120180#0033">120180.0033</a>) was identified in both. Angiography of the cerebral vessels in the mother revealed coiling on both internal carotids in the extracranial tract, which mimicked fibromuscular dysplasia as reported by <a href="#46" class="mim-tip-reference" title="Schievink, W. I., Limburg, M. &lt;strong&gt;Angiographic abnormalities mimicking fibromuscular dysplasia in a patient with Ehlers-Danlos syndrome, type IV. (Letter)&lt;/strong&gt; Neurosurgery 25: 482-483, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2771024/&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;2771024&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00006123-198909000-00033&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="2771024">Schievink and Limburg (1989)</a>. The phenotypically normal maternal grandmother was found to be mosaic for this mutation. The maternal grandfather and a maternal aunt each had an abdominal aortic aneurysm, the rupture of which was the cause of death in the latter at 40 years of age; the aneurysm in the grandfather was presumably an incidental finding, with a cause different from the vascular disease that the other members of the family inherited from the mosaic maternal grandmother. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2771024+12786757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Ehlers-Danlos Syndrome Type IV Variant</em></strong></p><p>
<a href="#19" class="mim-tip-reference" title="Kontusaari, S., Tromp, G., Kuivaniemi, H., Romanic, A. M., Prockop, D. J. &lt;strong&gt;A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms.&lt;/strong&gt; J. Clin. Invest. 86: 1465-1473, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2243125/&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;2243125&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI114863&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="2243125">Kontusaari et al. (1990)</a> studied a 37-year-old female captain in the U. S. Air Force who had a family history of sudden death due to rupture of thoracic or abdominal aortic aneurysms. She had mild hyperextensibility of joints and apparent arachnodactyly, with a hand-to-height ratio of 10.9% (upper limit of normal). She had a tendency to bruise easily, and the surgeon who had previously removed her appendix noted that her tissues seemed friable and bled easily, with the loss of 1 liter of blood during that operation. She had no history of joint dislocations, her skin had normal texture without unusual extensibility, and she did not have subluxation of the lens on slit-lamp examination. Analysis of the COL3A1 gene revealed heterozygosity for a missense mutation (G619R; <a href="/entry/120180#0002">120180.0002</a>) that was also found in pathology specimens from her mother and a maternal aunt, who died at age 34 years and 55 years, respectively, of aortic aneurysms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2243125" 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 34-year-old man with a history of thin skin and easy bruisability, who died of massive intrathoracic and intraabdominal hemorrhage, <a href="#18" class="mim-tip-reference" title="Kontusaari, S., Tromp, G., Kuivaniemi, H., Ladda, R. L., Prockop, D. J. &lt;strong&gt;Inheritance of an RNA splicing mutation (G(+1) IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Am. J. Hum. Genet. 47: 112-120, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2349939/&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;2349939&lt;/a&gt;]" pmid="2349939">Kontusaari et al. (1990)</a> identified heterozygosity for a splice site mutation in the COL3A1 gene (<a href="/entry/120180#0004">120180.0004</a>). At autopsy, no distinct aneurysm or bleeding point was identified, but microscopic sections of aorta revealed an apparent decrease in and disorganization of elastic fibers, and all the abdominal soft tissues appeared to be unusually friable. The proband's father and 1 brother had died of rupture of abdominal and thoracic aneurysms, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2349939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Genotype/Phenotype Correlations</strong>
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</h4>
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<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
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<p><a href="#48" class="mim-tip-reference" title="Schwarze, U., Schievink, W. I., Petty, E., Jaff, M. R., Babovic-Vuksanovic, D., Cherry, K. J., Pepin, M., Byers, P. H. &lt;strong&gt;Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Am. J. Hum. Genet. 69: 989-1001, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11577371/&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;11577371&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11577371[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/10.1086/324123&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="11577371">Schwarze et al. (2001)</a> studied 4 patients with EDS IV who presented with vascular aneurysm or rupture and were found to be haploinsufficient for a COL3A1 allele. They noted that in contrast to the severe phenotype in these patients, mice that are haploinsufficient for COL3A1 have no identified phenotype and individuals with null mutations in the dominant protein of a tissue, i.e., COL1A1 and COL2A1, have milder phenotypes than those caused by mutations that alter protein sequence. <a href="#48" class="mim-tip-reference" title="Schwarze, U., Schievink, W. I., Petty, E., Jaff, M. R., Babovic-Vuksanovic, D., Cherry, K. J., Pepin, M., Byers, P. H. &lt;strong&gt;Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Am. J. Hum. Genet. 69: 989-1001, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11577371/&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;11577371&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11577371[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/10.1086/324123&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="11577371">Schwarze et al. (2001)</a> suggested that the major effect of many of these dominant mutations in the 'minor' collagen genes may be expressed through protein deficiency rather than through incorporation of structurally altered molecules into fibrils. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11577371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Leistritz, D. F., Pepin, M. G., Schwarze U., Byers, P. H. &lt;strong&gt;COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy.&lt;/strong&gt; Genet. Med. 13: 717-722, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21637106/&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;21637106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182180c89&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="21637106">Leistritz et al. (2011)</a> reviewed the clinical and family histories of medical complications in 54 individuals from 19 families with COL3A1-null mutations. Compared with individuals with missense or exon-skipping mutations, they found that life span was extended, the age of first complication was delayed by almost 15 years, and major complications were limited to vascular events. Families were ascertained after a complication in a single individual, but only 28% of relatives, some of whom had reached their seventies or eighties without incident, had a complication and only 30% had minor clinical features of vascular Ehlers-Danlos syndrome type IV. <a href="#23" class="mim-tip-reference" title="Leistritz, D. F., Pepin, M. G., Schwarze U., Byers, P. H. &lt;strong&gt;COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy.&lt;/strong&gt; Genet. Med. 13: 717-722, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21637106/&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;21637106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e3182180c89&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="21637106">Leistritz et al. (2011)</a> concluded that null mutations of COL3A1 have reduced penetrance compared with missense and splicing mutations, and the phenotype seems to be limited almost entirely to vascular events. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21637106" 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="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a> reviewed clinical records for details of vascular, bowel, and organ complications in 1,231 individuals (630 index cases and 601 relatives) with vascular EDS. Missense and splice site mutations accounted for more than 90% of the 572 alterations that the authors identified in COL3A1. Median survival was 51 years but was influenced by gender (lower in men) and by the type of mutation. Although vascular EDS appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1. <a href="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a> concluded that these findings indicate that when counseling families, confirmation of the presence of a COL3A1 mutation and its nature can help evaluate the risks of complications. These data are also important factors in both the selection and allocation of individuals to appropriate arms in clinical trials to assess the effects of interventions. Among the 410 unique mutation sites identified by <a href="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a>, 69 had more than 1 family with the same mutation. Among these, 4 sites (c.1662+1G-A, IVS24+1G-A (32), c.547G-A, p.Gly183Ser, p.Gly16Ser in the triple helical domain (18), c.755G-T, p.Gly252Val, c.1347+1G-A, IVS20+1G-A (9), and Gly85Val in the triple helical domain (8)) accounted for 30% of recurrent mutations. There were 17 additional sites with more than 2 unrelated families with the same mutation. By mutation type, <a href="#36" class="mim-tip-reference" title="Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H. &lt;strong&gt;Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV).&lt;/strong&gt; Genet. Med. 16: 881-888, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24922459/&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;24922459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2014.72&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="24922459">Pepin et al. (2014)</a> found that survival was highest among patients with null mutations; second, by more severe and splice acceptor site mutations; third, by glycine substitution mutations; and fourth, by splice donor site mutations. The hazard ratio for a glycine change to any other amino acid was higher than that for null mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24922459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="diagnosis" class="mim-anchor"></a>
<h4 href="#mimDiagnosisFold" id="mimDiagnosisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Diagnosis</strong>
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<p><a href="#50" class="mim-tip-reference" title="Steinmann, B., Superti-Furga, A., Joller-Jemelka, H. I., Cetta, G., Byers, P. H. &lt;strong&gt;Ehlers-Danlos syndrome type IV--a subset of patients distinguished by low serum levels of the amino-terminal propeptide of type III procollagen.&lt;/strong&gt; Am. J. Med. Genet. 34: 68-71, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2816989/&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;2816989&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320340113&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="2816989">Steinmann et al. (1989)</a> suggested that determination of serum levels of procollagen type III aminopropeptide is a simple test for diagnosis and might be especially helpful in making the diagnosis in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2816989" 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="#16" class="mim-tip-reference" title="Johnson, P. H., Richards, A. J., Lloyd, J. C., Pope, F. M., Hopkinson, D. A. &lt;strong&gt;Efficient strategy for the detection of mutations in acrogeric Ehlers-Danlos syndrome type IV.&lt;/strong&gt; Hum. Mutat. 6: 336-342, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8680408/&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;8680408&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380060408&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="8680408">Johnson et al. (1995)</a> were successful in demonstrating mutations in all 13 patients with typical or acrogeric EDS IV using denaturing gradient gel electrophoresis (DGGE) in the study of PCR-amplified cDNA from the C-terminal domain of type III collagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8680408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Autio, P., Turpeinen, M., Risteli, J., Kallioinen, M., Kiistala, U., Oikarinen, A. &lt;strong&gt;Ehlers-Danlos type IV: non-invasive techniques as diagnostic support.&lt;/strong&gt; Brit. J. Derm. 137: 653-655, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9390355/&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;9390355&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1365-2133.1997.tb03811.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="9390355">Autio et al. (1997)</a> pictured the characteristic facial appearance, as well as the thin transparent skin over the anterior aspect of the chest and upper arms, of an EDS IV patient. They suggested B-mode ultrasonic techniques, in place of skin biopsy, as a useful noninvasive method for demonstrating thin skin. In addition, they concluded that the measurement of procollagen propeptides in body fluids is a valuable noninvasive method helpful in the diagnosis and classification of EDS. They confirmed the diagnosis of EDS IV in a patient by measuring type III amino-terminal procollagen propeptide levels in the skin interstitial fluid, i.e., suction blister fluid (SBF), and serum and the type I amino-terminal procollagen propeptide level in SBF. The serum concentration of the type III propeptide has been shown to be abnormally low or in the low normal range in EDS IV patients and well-correlated with the ability of the patient's cultured fibroblasts to secrete type III procollagen. In the patient reported, the serum concentration of the type III propeptide was low; however, the elimination of the type III propeptide molecule from the serum is a constant process and may be altered by factors such as abnormal liver function. Thus, the concentration of the type III propeptide in the SBF more accurately reflects an individual's synthesis of type III collagen. This value was abnormally low in the reported patient. In turn, the concentration of the type I propeptide in the SBF was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390355" 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="#37" class="mim-tip-reference" title="Pepin, M., Schwarze, U., Superti-Furga, A., Byers, P. H. &lt;strong&gt;Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type.&lt;/strong&gt; New Eng. J. Med. 342: 673-680, 2000. Note: Erratum: New Eng. J. Med. 344: 392 only, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10706896/&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;10706896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200003093421001&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="10706896">Pepin et al. (2000)</a> reviewed the clinical and family histories and the medical and surgical complications of 220 index patients with biochemically confirmed Ehlers-Danlos syndrome type IV and 199 of their affected relatives. They identified the underlying COL3A1 mutation in 135 index patients. Complications were rare in childhood; 25% of the index patients had a first complication by the age of 20 years, and more than 80% had at least 1 complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about one-quarter of complications but rarely led to death. Complications of pregnancy led to death in 12 of the 81 women who became pregnant. The types of complications were not associated with specific mutations in COL3A1. The authors urged that the diagnosis of EDS IV be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or visceral rupture. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10706896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>See Also:</strong>
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<a href="#Kontusaari1989" class="mim-tip-reference" title="Kontusaari, S., Kuivaniemi, H., Tromp, G., Grimwood, R., Prockop, D. J. &lt;strong&gt;A single base mutation in the type III procollagen gene (COL3A1) on chromosome 2q that causes familial aneurysms. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 51: 1024-1025, 1989.">Kontusaari et al. (1989)</a>; <a href="#Kuivaniemi1991" class="mim-tip-reference" title="Kuivaniemi, H., Tromp, G., Prockop, D. J. &lt;strong&gt;Genetic causes of aortic aneurysms: unlearning at least part of what the textbooks say.&lt;/strong&gt; J. Clin. Invest. 88: 1441-1444, 1991.">Kuivaniemi et al. (1991)</a>; <a href="#Liu1997" class="mim-tip-reference" title="Liu, X., Wu, H., Byrne, M., Krane, S., Jaenisch, R. &lt;strong&gt;Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development.&lt;/strong&gt; Proc. Nat. Acad. Sci. 94: 1852-1856, 1997.">Liu et al.
(1997)</a>; <a href="#Nicholls1988" class="mim-tip-reference" title="Nicholls, A. C., De Paepe, A., Narcisi, P., Dalgleish, R., De Keyser, F., Matton, M., Pope, F. M. &lt;strong&gt;Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree.&lt;/strong&gt; Hum. Genet. 78: 276-281, 1988.">Nicholls et al. (1988)</a>; <a href="#Roberts1984" class="mim-tip-reference" title="Roberts, D. L. L., Pope, F. M., Nicholls, A. C., Narcisi, P. &lt;strong&gt;Ehlers-Danlos syndrome type IV mimicking non-accidental injury in a child.&lt;/strong&gt; Brit. J. Derm. 111: 341-345, 1984.">Roberts et al. (1984)</a>
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Autio, P., Turpeinen, M., Risteli, J., Kallioinen, M., Kiistala, U., Oikarinen, A.
<strong>Ehlers-Danlos type IV: non-invasive techniques as diagnostic support.</strong>
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[<a href="https://doi.org/10.1111/j.1365-2133.1997.tb03811.x" target="_blank">Full Text</a>]
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Barabas, A. P.
<strong>Personal Communication.</strong>
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Barabas, A. P.
<strong>Ehlers-Danlos syndrome type IV. (Letter)</strong>
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[<a href="https://doi.org/10.1056/NEJM200008033430513" target="_blank">Full Text</a>]
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Boutouyrie, P., Germain, D. P., Fiessinger, J.-N., Laloux, B., Perdu, J., Laurent, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15007000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15007000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15007000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1161/01.CIR.0000121741.50315.C2" target="_blank">Full Text</a>]
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Byard, R. W., Keeley, F. W., Smith, C. R.
<strong>Type IV Ehlers-Danlos syndrome presenting as sudden infant death.</strong>
Am. J. Clin. Path. 93: 579-582, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2321591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2321591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2321591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/ajcp/93.4.579" target="_blank">Full Text</a>]
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<p class="mim-text-font">
Byers, P. H., Barsh, G. S., Holbrook, K. A.
<strong>Molecular mechanisms of connective tissue abnormalities in the Ehlers-Danlos syndrome.</strong>
Coll. Relat. Res. 1: 475-489, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6125299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6125299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6125299" 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/s0174-173x(81)80030-1" target="_blank">Full Text</a>]
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<a id="Byers1979" class="mim-anchor"></a>
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Byers, P. H., Holbrook, K. A., McGillivray, B., MacLeod, P. M., Lowry, R. B.
<strong>Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome.</strong>
Hum. Genet. 47: 141-150, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/437782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">437782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=437782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00273196" target="_blank">Full Text</a>]
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Byers, P. H.
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Cooper, R. R., Pedrini-Mille, A., Ponseti, I. V.
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<a id="De Paepe1987" class="mim-anchor"></a>
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De Paepe, A., Nicholls, A., Narcisi, P., De Keyser, F., Quatacker, J., Van Staey, M., Matton, M., Pope, F. M.
<strong>Ehlers-Danlos syndrome type I: a clinical and ultrastructural study of a family with reduced amounts of collagen type III.</strong>
Brit. J. Derm. 117: 89-97, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3651336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3651336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3651336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1365-2133.1987.tb04096.x" target="_blank">Full Text</a>]
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<a id="De Paepe1988" class="mim-anchor"></a>
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De Paepe, A., Van den Bossche, H., Mortier, G., Matton, M.
<strong>Les syndromes d'Ehlers-Danlos et de Marfan chez le jeune enfant.</strong>
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<a id="Fox1988" class="mim-anchor"></a>
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<p class="mim-text-font">
Fox, R., Pope, F. M., Narcisi, P., Nicholls, A. C., Kendall, B. E., Hourihan, M. D., Compston, D. A. S.
<strong>Spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome.</strong>
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[<a href="https://doi.org/10.1136/jnnp.51.7.984" target="_blank">Full Text</a>]
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<a id="Germain2004" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Germain, D. P., Herrera-Guzman, Y.
<strong>Vascular Ehlers-Danlos syndrome.</strong>
Ann. Genet. 47: 1-9, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15127738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15127738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15127738" 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.anngen.2003.07.002" target="_blank">Full Text</a>]
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<a id="Gilchrist1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gilchrist, D., Schwarze, U., Shields, K., MacLaren, L., Bridge, P. J., Byers, P. H.
<strong>Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives.</strong>
Am. J. Med. Genet. 82: 305-311, 1999.
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<a id="Johnson1995" class="mim-anchor"></a>
<div class="">
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Johnson, P. H., Richards, A. J., Lloyd, J. C., Pope, F. M., Hopkinson, D. A.
<strong>Efficient strategy for the detection of mutations in acrogeric Ehlers-Danlos syndrome type IV.</strong>
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[<a href="https://doi.org/10.1002/humu.1380060408" target="_blank">Full Text</a>]
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<a id="Kontusaari1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kontusaari, S., Kuivaniemi, H., Tromp, G., Grimwood, R., Prockop, D. J.
<strong>A single base mutation in the type III procollagen gene (COL3A1) on chromosome 2q that causes familial aneurysms. (Abstract)</strong>
Cytogenet. Cell Genet. 51: 1024-1025, 1989.
</p>
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<a id="Kontusaari1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kontusaari, S., Tromp, G., Kuivaniemi, H., Ladda, R. L., Prockop, D. J.
<strong>Inheritance of an RNA splicing mutation (G(+1) IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV.</strong>
Am. J. Hum. Genet. 47: 112-120, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2349939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2349939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2349939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI114863" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2003.00047.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI115452" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/GIM.0b013e3182180c89" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.94.5.1852" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/gim.2014.53" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1259/0007-1285-32-383-739" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00291676" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410380620" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1034/j.1399-0004.2003.00075.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/gim.2014.72" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM200003093421001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1445-5994.1998.tb02972.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.14.3.200" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(83)92631-4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.21828" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00194313" target="_blank">Full Text</a>]
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<strong>Ehlers-Danlos syndrome type IV mimicking non-accidental injury in a child.</strong>
Brit. J. Derm. 111: 341-345, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6477831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6477831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6477831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1365-2133.1984.tb04733.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Rudd1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rudd, N. L., Nimrod, C., Holbrook, K. A., Byers, P. H.
<strong>Pregnancy complications in type IV Ehlers-Danlos syndrome.</strong>
Lancet 321: 50-53, 1983. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6129381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6129381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6129381" 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/s0140-6736(83)91577-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="Schievink1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schievink, W. I., Limburg, M.
<strong>Angiographic abnormalities mimicking fibromuscular dysplasia in a patient with Ehlers-Danlos syndrome, type IV. (Letter)</strong>
Neurosurgery 25: 482-483, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2771024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2771024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2771024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00006123-198909000-00033" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Schwartz1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schwartz, R. C., Byers, P. H., Chu, M.-L., Weil, D., Ramirez, F., Tsipouras, P.
<strong>Ehlers-Danlos syndrome type IV (EDS IV): genetic linkage to the pro-alpha-1(III) collagen gene. (Abstract)</strong>
Am. J. Hum. Genet. 37: A173, 1985.
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Schwarze2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schwarze, U., Schievink, W. I., Petty, E., Jaff, M. R., Babovic-Vuksanovic, D., Cherry, K. J., Pepin, M., Byers, P. H.
<strong>Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV.</strong>
Am. J. Hum. Genet. 69: 989-1001, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11577371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11577371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11577371[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=11577371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/324123" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Sherry1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sherry, R. M., Fisch, A., Grey, D. P., Lubbock, C. A.
<strong>Embolization of a hepatoportal fistula in a patient with Ehlers-Danlos syndrome and colon perforation.</strong>
Surgery 111: 475-478, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1557695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1557695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1557695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Steinmann1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B., Superti-Furga, A., Joller-Jemelka, H. I., Cetta, G., Byers, P. H.
<strong>Ehlers-Danlos syndrome type IV--a subset of patients distinguished by low serum levels of the amino-terminal propeptide of type III procollagen.</strong>
Am. J. Med. Genet. 34: 68-71, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2816989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2816989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2816989" 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.1320340113" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Superti-Furga1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Gugler, E., Gitzelmann, R., Steinmann, B.
<strong>Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.</strong>
J. Biol. Chem. 263: 6226-6232, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2834369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2834369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2834369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Superti-Furga1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Royce, P. M., Gugler, E., Gitzelmann, R., Steinmann, B.
<strong>A structural defect of type III collagen causing Ehlers-Danlos syndrome type IV. (Abstract)</strong>
Pediat. Res. 20: 1043, 1986.
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Superti-Furga1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Saesseli, B., Steinmann, B., Bollinger, A.
<strong>Microangiopathy in Ehlers-Danlos syndrome type IV.</strong>
Int. J. Microcirc. Clin. Exp. 11: 241-247, 1992. Note: Erratum: Int. J. Microcirc. Clin. Exp. 11: 455 only, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1506129/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1506129</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1506129" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Superti-Furga1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B., Ramirez, F., Byers, P. H.
<strong>Molecular defects of type III procollagen in Ehlers-Danlos syndrome type IV.</strong>
Hum. Genet. 82: 104-108, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2722184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2722184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2722184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00284038" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Superti-Furga1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B.
<strong>Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule.</strong>
Biochem. Biophys. Res. Commun. 150: 140-147, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3337712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3337712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3337712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0006-291x(88)90497-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Superti-Furga1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B.
<strong>Ehlers-Danlos syndrome type IV: another temperature-dependent skin disorder? (Letter)</strong>
J. Am. Acad. Derm. 21: 323, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2768588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2768588</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2768588" 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/s0190-9622(89)70192-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="Tsipouras1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tsipouras, P., Byers, P. H., Schwartz, R. C., Chu, M.-L., Weil, D., Pepe, G., Cassidy, S. B., Ramirez, F.
<strong>Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen.</strong>
Hum. Genet. 74: 41-46, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2875936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2875936</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2875936" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00278783" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" 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>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Yost1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yost, B. A., Vogelsang, J. P., Lie, J. T.
<strong>Fatal hemoptysis in Ehlers-Danlos syndrome: old malady with a new curse.</strong>
Chest 107: 1465-1467, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7750352/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7750352</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7750352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1378/chest.107.5.1465" target="_blank">Full Text</a>]
</p>
</div>
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<div>
<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 1/27/2015
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Ada Hamosh - updated : 9/28/2012<br>Cassandra L. Kniffin - updated : 4/22/2011<br>Cassandra L. Kniffin - updated : 5/11/2010<br>Cassandra L. Kniffin - updated : 11/19/2009<br>Marla J. F. O'Neill - updated : 9/25/2009<br>Marla J. F. O'Neill - updated : 11/10/2005<br>Victor A. McKusick - updated : 8/24/2004<br>Victor A. McKusick - updated : 7/10/2003<br>Victor A. McKusick - updated : 4/22/2003<br>Deborah L. Stone - updated : 2/28/2002<br>Victor A. McKusick - updated : 9/27/2000<br>Victor A. McKusick - updated : 3/23/2000<br>Sonja A. Rasmussen - updated : 5/12/1999<br>Victor A. McKusick - updated : 8/24/1998<br>Victor A. McKusick - updated : 3/24/1998<br>Orest Hurko - updated : 3/7/1996
</span>
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<div>
<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/4/1986
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 07/18/2019
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carol : 03/05/2019<br>ckniffin : 03/04/2019<br>carol : 12/22/2017<br>carol : 12/21/2017<br>carol : 07/09/2016<br>carol : 5/17/2016<br>carol : 1/27/2015<br>carol : 9/5/2014<br>alopez : 10/2/2012<br>terry : 9/28/2012<br>terry : 6/20/2012<br>carol : 6/19/2012<br>carol : 5/30/2012<br>alopez : 1/20/2012<br>terry : 5/31/2011<br>wwang : 5/12/2011<br>ckniffin : 4/22/2011<br>carol : 8/13/2010<br>wwang : 5/13/2010<br>ckniffin : 5/11/2010<br>ckniffin : 5/11/2010<br>terry : 4/30/2010<br>wwang : 2/17/2010<br>carol : 1/21/2010<br>ckniffin : 11/19/2009<br>carol : 9/30/2009<br>carol : 9/28/2009<br>carol : 9/25/2009<br>terry : 1/13/2009<br>carol : 3/15/2007<br>alopez : 10/11/2006<br>terry : 9/20/2006<br>wwang : 11/10/2005<br>tkritzer : 9/2/2004<br>terry : 8/24/2004<br>carol : 12/3/2003<br>carol : 12/3/2003<br>tkritzer : 8/4/2003<br>tkritzer : 7/31/2003<br>terry : 7/10/2003<br>cwells : 4/28/2003<br>terry : 4/22/2003<br>carol : 4/4/2003<br>carol : 2/28/2002<br>mcapotos : 10/12/2000<br>mcapotos : 10/10/2000<br>terry : 9/27/2000<br>terry : 9/27/2000<br>carol : 8/1/2000<br>terry : 7/25/2000<br>mcapotos : 4/14/2000<br>mcapotos : 4/13/2000<br>terry : 3/23/2000<br>carol : 2/17/2000<br>carol : 5/12/1999<br>terry : 4/30/1999<br>carol : 11/15/1998<br>carol : 8/25/1998<br>terry : 8/24/1998<br>psherman : 3/24/1998<br>dholmes : 3/6/1998<br>mark : 5/15/1996<br>terry : 5/10/1996<br>terry : 4/15/1996<br>mark : 3/7/1996<br>terry : 2/23/1996<br>mark : 7/11/1995<br>pfoster : 1/17/1995<br>davew : 8/25/1994<br>carol : 5/13/1994<br>warfield : 4/8/1994<br>mimadm : 2/21/1994
</span>
</div>
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<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
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<h3>
<span class="mim-font">
<strong>#</strong> 130050
</span>
</h3>
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<div>
<h3>
<span class="mim-font">
EHLERS-DANLOS SYNDROME, VASCULAR TYPE; EDSVASC
</span>
</h3>
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<div>
<br />
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<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
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<div>
<h4>
<span class="mim-font">
EHLERS-DANLOS SYNDROME, TYPE IV, AUTOSOMAL DOMINANT; EDS4<br />
EDS IV<br />
EHLERS-DANLOS SYNDROME, ARTERIAL TYPE<br />
EHLERS-DANLOS SYNDROME, ECCHYMOTIC TYPE<br />
EHLERS-DANLOS SYNDROME, SACK-BARABAS TYPE
</span>
</h4>
</div>
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<div>
<br />
</div>
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<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 17025000; &nbsp;
<strong>ICD10CM:</strong> Q79.63; &nbsp;
<strong>ORPHA:</strong> 286; &nbsp;
<strong>DO:</strong> 14756; &nbsp;
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed 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">
2q32.2
</span>
</td>
<td>
<span class="mim-font">
Ehlers-Danlos syndrome, vascular type
</span>
</td>
<td>
<span class="mim-font">
130050
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
COL3A1
</span>
</td>
<td>
<span class="mim-font">
120180
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
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<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
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<p>A number sign (#) is used with this entry because vascular-type Ehlers-Danlos syndrome (EDSVASC) is caused by heterozygous mutation in the COL3A1 gene (120180) on chromosome 2q32.</p><p>Biallelic mutation in the COL3A1 gene causes polymicrogyria with or without vascular EDS (PMGVEDS; 618343).</p>
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<strong>Description</strong>
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<p>The vascular type of Ehlers-Danlos syndrome is characterized by the major complications of arterial and bowel rupture, uterine rupture during pregnancy, and the clinical features of easy bruising, thin skin with visible veins, and characteristic facial features (summary by Leistritz et al., 2011). Joint hypermobility is largely limited to the digits, and skin hyperextensibility is minimal or absent (McKusick, 1972). </p>
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<strong>Clinical Features</strong>
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<p>Superti-Furga et al. (1988) provided the first description of a mutation in the COL3A1 gene in type IV EDS. The proband was 22 years old; his father was affected with the same disorder and had died at age 34 years. He had been hospitalized for bleeding in the anterior abdominal wall and retroperitoneally following minor trauma. He went into cardiac arrest; open-chest cardiac massage resulted in avulsion of the heart from the superior vena cava with massive intrathoracic bleeding and death. </p><p>Type III procollagen is stored in dermal fibroblasts which show markedly dilated endoplasmic reticulum. Byers et al. (1979) emphasized the heterogeneity of EDS IV. Of 2 patients only 1 showed dilated endoplasmic reticulum. Probably a defect in type III collagen is a common feature. One of their patients showed keloid formation, a seemingly paradoxical feature that McKusick (1979) also observed in this disorder. One patient had had spontaneous pneumothorax as well as spontaneous rupture of the bowel. </p><p>Pope et al. (1980) reported an apparent dominant form of EDS IV (in father and daughter). The acrogeric appearance of the skin of the hands was particularly striking in the 37-year-old father. A third patient (their patient 1) had severe acrogeric EDS IV. At age 7 she had been presented at the Section of Dermatology of the Royal Society of Medicine (Morris, 1957). At age 25 she suffered spontaneous rupture of the splenic artery and 3 years later had rupture of a left renal artery aneurysm. At age 29 she showed the typical facies and hand changes of acrogeria. The skin over the nose and ears was tight like that in scleroderma. Acroosteolysis was present. Chemical studies showed striking deficiency of type III collagen in all 3 cases. See 120180.0015. </p><p>In an 18-year-old girl whom they considered to have EDS I, De Paepe et al. (1987) found large, irregular collagen fibers by light microscopy of skin biopsies, with the same finding in the affected father. Electron microscopy showed variation in the diameter and shape of collagen fibrils as well as slight dilatation of the rough endoplasmic reticulum of fibroblasts in father and daughter. In both instances, the findings in the unaffected mother were normal. Synthesis of type III collagen was reduced to 50% of normal in the father and daughter. The patient had perhaps a greater tendency to bruising than do many EDS I patients. The abnormality in type III collagen suggested the diagnosis of EDS IV. </p><p>Fox et al. (1988) described a man who developed a spontaneous pulsating tinnitus in his left ear at the age of 20.5 years; he discovered accidentally that this noise could be stopped by firm pressure over the left side of the neck. Left-sided periorbital swelling, reddening of the conjunctiva, and ocular pain developed 6 months later, with left-sided pulsatile proptosis and a loud vascular bruit over the left orbit. Signs of EDS IV included thin nose and lips, hyperextensible joints, lax or thin skin with prominent venous markings, and small linear telangiectases on the trunk. There was a history of rectal bleeding attributed to multiple colonic diverticula. The patient was found to have a deficiency of type III collagen. The carotid-cavernous fistula was closed by means of a balloon catheter. Fox et al. (1988) referred to 5 previously reported cases of the Ehlers-Danlos syndrome presenting as spontaneous carotid-cavernous fistula. </p><p>In a group of 14 families, Rudd et al. (1983) identified 20 women with EDS IV. The diagnosis was confirmed in at least 1 member of each family by demonstration of reduced production of type III collagen by dermal fibroblasts in vitro. Of the 20 women, 10 had been pregnant and 5 had died of pregnancy-related complications. The overall risk of death in each pregnancy was 25% in this series. Pregnancy-related complications included rupture of bowel, aorta, vena cava or uterus, vaginal laceration, and postpartum uterine hemorrhage. Nine of the families had 29 affected persons in an autosomal dominant pedigree pattern; the remaining 5 families had a single case. Pope and Nicholls (1983) took a less pessimistic view of pregnancy in EDS IV. </p><p>Byard et al. (1990) ascribed the 'sudden infant death syndrome' in a previously healthy 5-month-old female infant to type IV Ehlers-Danlos syndrome leading to spontaneous subarachnoid hemorrhage. The skin and aorta at postmortem showed a deficiency of type III collagen. There was no parental consanguinity and no family history of EDS, and both parents were aged 25. There were no gross features of EDS IV and the diagnosis was based exclusively on the finding that type III collagen in aorta and skin was reduced. Sherry et al. (1992) described a 16-year-old boy with EDS IV who developed a hepatoportal fistula 9 days after sigmoid colectomy and colostomy were performed for spontaneous rupture of the colon. The fistula was successfully occluded angiographically with a transcatheter coil </p><p>In 2 patients with inherited EDS IV, Superti-Furga et al. (1992) demonstrated evidence of microangiopathy of skin capillaries with microbleedings, microaneurysms, and increased transcapillary diffusion. </p><p>In a series of 10 patients, Lewkonia and Pope (1985) found several with peripheral joint contractures and 3 who had acroosteolysis involving both fingers and toes. The simulation of chronic inflammatory joint disease was pointed out. Newton and Carpenter (1959) also reported acroosteolysis in EDS but it is not clear that the mother and daughter that they reported had type IV. They pointed out that the dislocation of the thumbs and other fingers may contribute to the simulation of rheumatoid arthritis. </p><p>Yost et al. (1995) described a 27-year-old man with EDS type IV who had recurrent and eventually fatal pulmonary hemorrhages. This had apparently not been previously described. North et al. (1995) reviewed the cerebral vascular complications in 202 individuals with molecularly confirmed type IV Ehlers Danlos syndrome. Of these, 19 individuals had cerebral vascular complications which included intracranial aneurysms, spontaneous carotid cavernous sinus fistulas, and dissection of cervical arteries. The mean age at presentation of the cerebral vascular complication was 28.3 years ranging from 17 to 48. </p><p>Phan et al. (1998) described a 39-year-old man with known EDS IV who presented with massive spontaneous hemothorax due to ruptured internal mammary artery aneurysm. He had first presented in his twenties with right renal infarction; 3 years later he underwent partial left nephrectomy for left renal infarction, and an aneurysm of the left renal artery was excised and the artery replaced. In addition to joint hypermobility, he had elastosis perforans serpiginosa. Emergency anterolateral thoracotomy for ligation of an abnormally fragile left internal mammary artery proximal to the aneurysm and drainage of an extensive hemothorax was accomplished successfully and postoperative recovery was uneventful. </p><p>Commenting on the report of Pepin et al. (2000), Barabas (2000) stated that in his experience, teenage boys are at high risk for arterial rupture, which is often fatal. He suggested that this may be because during the prepubertal growth spurt the defective collagen is further weakened. He stated further that patients who undergo surgery are prone to arterial rupture in the postoperative period. Pepin et al. (2000) had commented that preexisting aneurysms are only occasionally documented in patients who have arterial ruptures. Barabas (2000) suggested that this is because the patients with EDS type IV do not have true aneurysms. Aneurysms, if present, follow arterial tears and are walled-in hematomas or pseudoaneurysms. Barabas (2000) also drew attention to the danger of varicose vein surgery in unrecognized cases of EDS type IV, since the extreme fragility of all blood vessels can lead to loss of a limb or even loss of life. </p><p>Kroes et al. (2003) described a mother and son with EDS type IV and unusual congenital anomalies. The mother had amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephalus; the son had esophageal atresia and hydrocephalus. The family was also anomalous in that protein analysis of collagen III in cultured fibroblasts of the mother showed no abnormalities; however, DNA analysis of the COL3A1 gene revealed a pathogenic mutation (120180.0031) in both the mother and the son. The relationship between the COL3A1 mutation and the congenital anomalies was not clear. The experience emphasized the importance of performing both collagen protein analysis and DNA analysis of COL3A1. </p><p>In 16 patients with EDS type IV and 16 age-, gender-, and blood pressure-matched controls, Boutouyrie et al. (2004) measured circumferential wall stress in an elastic (common carotid) and a muscular (radial) artery. In the carotid artery, steady circumferential wall stress was 43% higher in EDS patients than in controls, pulsatile circumferential wall stress was 22% higher, and carotid intima-media thickness was 32% lower (p less than 0.001 for all findings). Carotid internal diameter and radial artery parameters were not significantly different between the 2 groups. Boutouyrie et al. (2004) concluded that the abnormally low intima-media thickness of elastic arteries in EDS IV patients generates higher wall stress, which may increase the risk of arterial dissection and rupture. </p><p>Germain and Herrera-Guzman (2004) provided an extensive review of EDS IV. </p><p>Murray et al. (2014) reported pregnancy-related complications and deaths in women with vascular Ehlers-Danlos syndrome. Pregnancy-related deaths occurred in 30 (5.3%) of 565 deliveries. There was no difference in Kaplan-Meier survival curves between parous and nulliparous women with vascular EDS. Interviews with 39 women indicated that 46% of deliveries were uncomplicated. The most common complications were third- or fourth-degree lacerations in 20% and preterm delivery in 19%. Life-threatening complications occurred in 14.5% of deliveries and included arterial dissection/rupture (9.2%), uterine rupture (2.6%), and surgical complications (2.6%). There were 5 maternal deaths (6.5%) in 76 deliveries. </p><p>Pepin et al. (2014) reviewed clinical records from 1,231 individuals with vascular EDS and found median survival of 51 years; this was influenced by gender (lower in men) and by the type of mutation. Aortic aneurysm, dissection, or rupture was the leading single vascular complication (22%) recorded, leading to death in 68% of patients. Coronary artery aneurysm, dissection, or rupture was described in 25 individuals (9 males and 16 females); the mean age of the event was 30.8 years (25.0 for males and 33.5 for females). Twenty-seven carotid cavernous sinus fistulae were described (22 in females, 5 in males), with mean age of event at 30.9 years. Lethal cerebral vascular accidents without detailed description were reported in 15 of the 38 individuals who suffered 'intracranial' events. There were 181 bowel perforations described in this cohort: 117 (65%) colon or bowel perforations; 52 (29%) sigmoid colon; 8 (4%) small bowel; and 4 (2%) esophagus or stomach. Four birth defects occurred with a significantly greater frequency than the currently estimated prevalence in the United States (p less than 0.01, Z-test). Clubfoot or unilateral or bilateral defect was recorded in 8% of study subjects. Congenital hip dislocation, limb deficiency, and amniotic band were recorded in roughly 1% of patients, which was well above the estimated US prevalence. Pepin et al. (2014) identified 295 individuals less than 18 years of age with vascular EDS; 174 (60%) were tested in the presence of a positive family history. Of those 174, 13% had experienced a major complication, and the mean age of testing was 8 years. Among individuals less than 18 years of age with a negative family history, the proportion ascertained on the basis of a major complication was greater (52%), and the age of testing was older (mean of 11.5 years). In the absence of a positive family history or a major complication, the features most commonly identified as the reason for testing were easy bruising, thin skin, and joint hypermobility, in combination with clubfoot. </p>
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<strong>Biochemical Features</strong>
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<p>In studies of cell strains from 8 cases of EDS IV, Superti-Furga et al. (1989) found evidence in 7 of structural defects in half of the type III procollagen chains synthesized, such as deletions or amino acid substitutions, which cause delayed formation and destabilization of the collagen triple helix and, as a consequence, reduced secretion of the molecule. In 3 of the families the inheritance was demonstrably autosomal dominant. One patient who had been thought to have a recessively inherited form of EDS IV (Pope et al., 1977) was found to have normal mRNA levels in the cells and secretion of a small amount of normal type III collagen, compatible with heterozygosity for a mutation in the COL3A1 gene. Because type III procollagen is a homotrimer, a structural defect in one-half of newly synthesized pro-alpha-1(III) chains will result in assembly of one-eighth normal and seven-eighths abnormal procollagen molecules. The mutant procollagen molecules described by Superti-Furga and Steinmann (1988) and Superti-Furga et al. (1986, 1988) had decreased thermal stability, were less efficiently secreted, and were not normally processed. </p><p>Steinmann et al. (1989) found that serum levels of procollagen type III aminopropeptide, a peptide released during conversion of type III procollagen to collagen, were abnormally low in 6 of 10 patients with EDS IV and low-normal in 4 other such patients. The serum levels correlated with the amount of type III procollagen secreted by the patients' cultured fibroblasts. Byers et al. (1981) reviewed the state of knowledge about collagen defects in the several forms of the Ehlers-Danlos syndrome. </p>
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<strong>Other Features</strong>
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<p>Byers et al. (1979) demonstrated a predominance of collagen fibers of small diameter in EDS IV with or without intracellular accumulation. Dilation of the endoplasmic reticulum is a normal finding in plasma cells, where immunoglobin is the storage material. It is an abnormal finding in hepatocytes in alpha-1-antitrypsin deficiency (613490), and in chondrocytes in pseudoachondroplasia (177170) (Maynard et al., 1972) and metaphyseal dysostosis, presumably of the Murk Jansen type (156400) (Cooper et al., 1973). </p><p>Temperature effects on the rate of synthesis and/or the stability of the collagen would account well for the acrogeric appearance of the hands and face with pinched nose and atrophic skin over the ears that is displayed by some patients (see fig. 6-10, p. 311, in McKusick, 1972).</p><p>Superti-Furga and Steinmann (1989) expanded the possibility that this disorder is a temperature-dependent condition and that the atrophic changes of the skin on the hands, ears, and nose can be so explained. The suggestion was based on their demonstration that the structurally abnormal type III procollagen, which is retained within fibroblasts at 37 degrees C, can be secreted sufficiently when the temperature is lowered to 32 degrees C or below. They suggested that the presence of defective molecules in the extracellular space leads to disorganization of collagen fibrils and therefore to more pronounced skin changes in the areas of lower skin temperature. </p><p>Voermans et al. (2009) performed a cross-sectional study on the presence of neuromuscular symptoms among 40 patients with various forms of EDS. Ten patients each were analyzed with classic type I EDS (130000), vascular EDS, hypermobility EDS (130020), and TNX-deficient EDS (606408). 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>Prontera et al. (2010) reported a 42-year old Italian man with a complex EDS phenotype caused by a 13.7-Mb de novo heterozygous deletion of chromosome 2q23.3-q31.2 resulting in deletion of the COL3A1, COL5A2 (120190), and myostatin (MSTN; 601788) genes. Loss of function mutations in COL3A1 and COL5A2 cause EDS types IV and I, respectively. Haploinsufficiency for MSTN results in overgrowth of skeletal muscle. Due to the monosomy for MSTN, the patient had 'an exceptional constitutional muscular mass,' without muscle weakness, myalgia, or easy fatigability. He also had no generalized joint hypomobility or recurrent joint dislocation; symptoms of EDS were limited to recurrent inguinal hernias and mild mitral valve prolapse. Prontera et al. (2010) hypothesized that haploinsufficiency for the MSTN allele exerted a protective effect again EDS clinical manifestations in this patient. The findings also indicated that there is direct involvement of muscle damage in EDS and that care of muscle function in these patients may be beneficial. </p>
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<strong>Inheritance</strong>
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<p>Barabas (1972) reported a family in which the mother and a 16-year-old brother died of aortic rupture and the proband had frequent hematomata and at least one intraperitoneal bleed. The transmission pattern was consistent with autosomal dominant inheritance. Barabas (1975), whose name along with Sack's is applied eponymically to this condition, later reported 3 sporadic and 2 familial cases. In 1 family the mother was affected and died of a tear in her abdominal aorta following her fourth pregnancy. The eldest boy died at the age of 16 of similar complications. A daughter 'has survived several major arterial catastrophes.' The inheritance appeared to be dominant in the other family also. </p><p>Byers (1980) identified 4 autosomal dominant families. In 1 kindred a father and his son and daughter were affected; the father and daughter died of catastrophes. Several members of the next generation are also affected. Two autosomal dominant forms may exist: one with and one without dilated endoplasmic reticulum. These may be allelic disorders, however; in AAT deficiency, similar forms with and without accumulation are observed.</p><p>Superti-Furga et al. (1989) supported the view that the great majority of cases of EDS IV have autosomal dominant inheritance. </p>
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<strong>Mapping</strong>
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<p>Although the lod score (1.8 at 0.0 recombination) did not achieve the level of 3.0, Schwartz et al. (1985) could conclude from linkage studies with a COL3A1 probe that the collagen III gene is probably mutant in a 3-generation family with EDS IV. Tsipouras et al. (1986) reported further on the study presented in abstract by Schwartz et al. (1985). Findings in 2 kindreds indicated linkage. The lod score was 2.10 at theta = 0.00 in their family A and 0.30 at theta = 0.00 in their family B. Biochemically, the defect was somewhat different in the 2 families. Linkage analysis in a large Belgian family segregating autosomal dominant Ehlers-Danlos syndrome type IV was consistent with linkage of the EDS IV phenotype to the COL3A1 locus. However, no abnormality was detected in the type III collagen produced by the patients, and immunofluorescent and tissue analysis demonstrated significant amounts of type III collagen in the tissues. </p><p>De Paepe et al. (1988) described a kindred with EDS IV in 11 members of 3 generations with numerous examples of male-to-male transmission. Deficiency in the synthesis of type III collagen was identified in cultured skin fibroblasts. By use of a RFLP associated with the COL3A1 gene, tight linkage was found between the gene and the disease; no definite recombinant was identified. </p>
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<strong>Molecular Genetics</strong>
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<p>Superti-Furga and Steinmann (1988) and Superti-Furga et al. (1986, 1988) showed that a patient with severe, dominantly inherited EDS IV had a deletion of 3.3 kb in the triple-helical coding domain of 1 of the 2 genes for the pro-alpha-chains of type III collagen. His cultured skin fibroblasts contained equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesized both normal and shortened procollagen chains. In procollagen molecules containing 1 or more shortened chains, a triple helix was formed with a length of only about 780 amino acids. The mutant procollagen molecules had decreased thermal stability, were less efficiently secreted, and were not normally processed. This was the first description of the molecular lesion in the COL3A1 gene in a case of EDS type IV. </p><p>In affected members of the family reported by Fox et al. (1988), Richards et al. (1992) described a gly847-to-glu mutation of the COL3A1 gene (120180.0014). This family included an unaffected member who was mosaic for the mutation. Kontusaari et al. (1992) described mosaicism for a mutation in the COL3A1 gene in the asymptomatic mother of a patient with EDS type IV (120180.0015). Milewicz et al. (1993) found heterozygosity for a 2-kb deletion in the COL3A1 gene in a severely affected teenaged girl whose asymptomatic father was mosaic for the same deletion. Milewicz et al. (1993) gave a useful summary of the numerous autosomal dominant or X-linked recessive disorders in which this phenomenon has been observed. </p><p>Gilchrist et al. (1999) identified a gly571-to-ser substitution in the triple helical domain of the products of one COL3A1 allele (120180.0026) in a large family with a milder phenotype than that typically associated with EDS IV. Clinical presentation in some of the affected members occurred at a later age than usual. Longevity was longer than that seen in many families, and there was less pregnancy-associated morbidity or mortality than that found in some families. The authors suggested that some clinical aspects of EDS IV may be related to the nature of the mutation and its effect on the behavior of the protein. </p><p>Palmeri et al. (2003) characterized 7 members of a family with EDS IV. The index patient, a young woman with an acrogeric face, suffered chronic muscle pain and cramps, Achilles tendon retraction, finger flexion contractures, and seizures. The mother had similar features and had experienced an ischemic stroke at the age of 43 years. A gly883-to-val mutation in the COL3A1 gene (120180.0033) was identified in both. Angiography of the cerebral vessels in the mother revealed coiling on both internal carotids in the extracranial tract, which mimicked fibromuscular dysplasia as reported by Schievink and Limburg (1989). The phenotypically normal maternal grandmother was found to be mosaic for this mutation. The maternal grandfather and a maternal aunt each had an abdominal aortic aneurysm, the rupture of which was the cause of death in the latter at 40 years of age; the aneurysm in the grandfather was presumably an incidental finding, with a cause different from the vascular disease that the other members of the family inherited from the mosaic maternal grandmother. </p><p><strong><em>Ehlers-Danlos Syndrome Type IV Variant</em></strong></p><p>
Kontusaari et al. (1990) studied a 37-year-old female captain in the U. S. Air Force who had a family history of sudden death due to rupture of thoracic or abdominal aortic aneurysms. She had mild hyperextensibility of joints and apparent arachnodactyly, with a hand-to-height ratio of 10.9% (upper limit of normal). She had a tendency to bruise easily, and the surgeon who had previously removed her appendix noted that her tissues seemed friable and bled easily, with the loss of 1 liter of blood during that operation. She had no history of joint dislocations, her skin had normal texture without unusual extensibility, and she did not have subluxation of the lens on slit-lamp examination. Analysis of the COL3A1 gene revealed heterozygosity for a missense mutation (G619R; 120180.0002) that was also found in pathology specimens from her mother and a maternal aunt, who died at age 34 years and 55 years, respectively, of aortic aneurysms. </p><p>In a 34-year-old man with a history of thin skin and easy bruisability, who died of massive intrathoracic and intraabdominal hemorrhage, Kontusaari et al. (1990) identified heterozygosity for a splice site mutation in the COL3A1 gene (120180.0004). At autopsy, no distinct aneurysm or bleeding point was identified, but microscopic sections of aorta revealed an apparent decrease in and disorganization of elastic fibers, and all the abdominal soft tissues appeared to be unusually friable. The proband's father and 1 brother had died of rupture of abdominal and thoracic aneurysms, respectively. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Schwarze et al. (2001) studied 4 patients with EDS IV who presented with vascular aneurysm or rupture and were found to be haploinsufficient for a COL3A1 allele. They noted that in contrast to the severe phenotype in these patients, mice that are haploinsufficient for COL3A1 have no identified phenotype and individuals with null mutations in the dominant protein of a tissue, i.e., COL1A1 and COL2A1, have milder phenotypes than those caused by mutations that alter protein sequence. Schwarze et al. (2001) suggested that the major effect of many of these dominant mutations in the 'minor' collagen genes may be expressed through protein deficiency rather than through incorporation of structurally altered molecules into fibrils. </p><p>Leistritz et al. (2011) reviewed the clinical and family histories of medical complications in 54 individuals from 19 families with COL3A1-null mutations. Compared with individuals with missense or exon-skipping mutations, they found that life span was extended, the age of first complication was delayed by almost 15 years, and major complications were limited to vascular events. Families were ascertained after a complication in a single individual, but only 28% of relatives, some of whom had reached their seventies or eighties without incident, had a complication and only 30% had minor clinical features of vascular Ehlers-Danlos syndrome type IV. Leistritz et al. (2011) concluded that null mutations of COL3A1 have reduced penetrance compared with missense and splicing mutations, and the phenotype seems to be limited almost entirely to vascular events. </p><p>Pepin et al. (2014) reviewed clinical records for details of vascular, bowel, and organ complications in 1,231 individuals (630 index cases and 601 relatives) with vascular EDS. Missense and splice site mutations accounted for more than 90% of the 572 alterations that the authors identified in COL3A1. Median survival was 51 years but was influenced by gender (lower in men) and by the type of mutation. Although vascular EDS appears to be genetically homogeneous, allelic heterogeneity is marked, and the natural history varies with gender and type of mutation in COL3A1. Pepin et al. (2014) concluded that these findings indicate that when counseling families, confirmation of the presence of a COL3A1 mutation and its nature can help evaluate the risks of complications. These data are also important factors in both the selection and allocation of individuals to appropriate arms in clinical trials to assess the effects of interventions. Among the 410 unique mutation sites identified by Pepin et al. (2014), 69 had more than 1 family with the same mutation. Among these, 4 sites (c.1662+1G-A, IVS24+1G-A (32), c.547G-A, p.Gly183Ser, p.Gly16Ser in the triple helical domain (18), c.755G-T, p.Gly252Val, c.1347+1G-A, IVS20+1G-A (9), and Gly85Val in the triple helical domain (8)) accounted for 30% of recurrent mutations. There were 17 additional sites with more than 2 unrelated families with the same mutation. By mutation type, Pepin et al. (2014) found that survival was highest among patients with null mutations; second, by more severe and splice acceptor site mutations; third, by glycine substitution mutations; and fourth, by splice donor site mutations. The hazard ratio for a glycine change to any other amino acid was higher than that for null mutations. </p>
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<strong>Diagnosis</strong>
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<p>Steinmann et al. (1989) suggested that determination of serum levels of procollagen type III aminopropeptide is a simple test for diagnosis and might be especially helpful in making the diagnosis in children. </p><p>Johnson et al. (1995) were successful in demonstrating mutations in all 13 patients with typical or acrogeric EDS IV using denaturing gradient gel electrophoresis (DGGE) in the study of PCR-amplified cDNA from the C-terminal domain of type III collagen. </p><p>Autio et al. (1997) pictured the characteristic facial appearance, as well as the thin transparent skin over the anterior aspect of the chest and upper arms, of an EDS IV patient. They suggested B-mode ultrasonic techniques, in place of skin biopsy, as a useful noninvasive method for demonstrating thin skin. In addition, they concluded that the measurement of procollagen propeptides in body fluids is a valuable noninvasive method helpful in the diagnosis and classification of EDS. They confirmed the diagnosis of EDS IV in a patient by measuring type III amino-terminal procollagen propeptide levels in the skin interstitial fluid, i.e., suction blister fluid (SBF), and serum and the type I amino-terminal procollagen propeptide level in SBF. The serum concentration of the type III propeptide has been shown to be abnormally low or in the low normal range in EDS IV patients and well-correlated with the ability of the patient's cultured fibroblasts to secrete type III procollagen. In the patient reported, the serum concentration of the type III propeptide was low; however, the elimination of the type III propeptide molecule from the serum is a constant process and may be altered by factors such as abnormal liver function. Thus, the concentration of the type III propeptide in the SBF more accurately reflects an individual's synthesis of type III collagen. This value was abnormally low in the reported patient. In turn, the concentration of the type I propeptide in the SBF was normal. </p><p>Pepin et al. (2000) reviewed the clinical and family histories and the medical and surgical complications of 220 index patients with biochemically confirmed Ehlers-Danlos syndrome type IV and 199 of their affected relatives. They identified the underlying COL3A1 mutation in 135 index patients. Complications were rare in childhood; 25% of the index patients had a first complication by the age of 20 years, and more than 80% had at least 1 complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about one-quarter of complications but rarely led to death. Complications of pregnancy led to death in 12 of the 81 women who became pregnant. The types of complications were not associated with specific mutations in COL3A1. The authors urged that the diagnosis of EDS IV be considered in young people who come to medical attention because of uterine rupture during pregnancy or arterial or visceral rupture. </p>
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<strong>See Also:</strong>
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</h4>
<span class="mim-text-font">
Kontusaari et al. (1989); Kuivaniemi et al. (1991); Liu et al.
(1997); Nicholls et al. (1988); Roberts et al. (1984)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
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</span>
</h4>
<div>
<p />
</div>
<div>
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<strong>Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives.</strong>
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Kontusaari, S., Tromp, G., Kuivaniemi, H., Ladda, R. L., Prockop, D. J.
<strong>Inheritance of an RNA splicing mutation (G(+1) IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV.</strong>
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Kontusaari, S., Tromp, G., Kuivaniemi, H., Romanic, A. M., Prockop, D. J.
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Kontusaari, S., Tromp, G., Kuivaniemi, H., Stolle, C., Pope, F. M., Prockop, D. J.
<strong>Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother.</strong>
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<p class="mim-text-font">
Kroes, H. Y., Pals, G., van Essen, A. J.
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[Full Text: https://doi.org/10.1034/j.1399-0004.2003.00047.x]
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Kuivaniemi, H., Tromp, G., Prockop, D. J.
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J. Clin. Invest. 88: 1441-1444, 1991.
[PubMed: 1939638]
[Full Text: https://doi.org/10.1172/JCI115452]
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<li>
<p class="mim-text-font">
Leistritz, D. F., Pepin, M. G., Schwarze U., Byers, P. H.
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<p class="mim-text-font">
Lewkonia, R. M., Pope, F. M.
<strong>Joint contractures and acroosteolysis in Ehlers-Danlos syndrome type IV.</strong>
J. Rheum. 12: 140-144, 1985.
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<li>
<p class="mim-text-font">
Liu, X., Wu, H., Byrne, M., Krane, S., Jaenisch, R.
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Maynard, J. A., Cooper, R. R., Ponseti, I. V.
<strong>A unique rough surfaced endoplasmic reticulum inclusion in pseudoachondroplasia.</strong>
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<p class="mim-text-font">
McKusick, V. A.
<strong>Heritable Disorders of Connective Tissue. (4th ed.)</strong>
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</p>
</li>
<li>
<p class="mim-text-font">
Mckusick, V. A.
<strong>Personal Communication.</strong>
Baltimore, Md. 1979.
</p>
</li>
<li>
<p class="mim-text-font">
Milewicz, D. M., Witz, A. M., Smith, A. C. M., Manchester, D. K., Waldstein, G., Byers, P. H.
<strong>Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring.</strong>
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<p class="mim-text-font">
Morris, D.
<strong>Acrogeria.</strong>
J. Roy. Soc. Med. 50: 330-331, 1957.
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Murray, M. L., Pepin, M., Peterson, S., Byers, P. H.
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Newton, T. H., Carpenter, M. E.
<strong>Ehlers-Danlos syndrome with acro-osteolysis.</strong>
Brit. J. Radiol. 32: 739-743, 1959.
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[Full Text: https://doi.org/10.1259/0007-1285-32-383-739]
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Nicholls, A. C., De Paepe, A., Narcisi, P., Dalgleish, R., De Keyser, F., Matton, M., Pope, F. M.
<strong>Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree.</strong>
Hum. Genet. 78: 276-281, 1988.
[PubMed: 3162228]
[Full Text: https://doi.org/10.1007/BF00291676]
</p>
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<p class="mim-text-font">
North, K. N., Whiteman, D. A. H., Pepin, M. G., Byers, P. H.
<strong>Cerebrovascular complications in Ehlers-Danlos syndrome type IV.</strong>
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Palmeri, S., Mari, F., Meloni, I., Malandrini, A., Ariani, F., Villanova, M., Pompilio, A., Schwarze, U., Byers, P. H., Renieri, A.
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Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., Byers, P. H.
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Pepin, M., Schwarze, U., Superti-Furga, A., Byers, P. H.
<strong>Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type.</strong>
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[PubMed: 10706896]
[Full Text: https://doi.org/10.1056/NEJM200003093421001]
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Phan, T. G., Sakulsaengprapha, A., Wilson, M., Wing, R.
<strong>Ruptured internal mammary artery aneurysm presenting as massive spontaneous haemothorax in a patient with Ehlers-Danlos syndrome. (Letter)</strong>
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Pope, F. M., Martin, G. R., McKusick, V. A.
<strong>Inheritance of Ehlers-Danlos type IV syndrome.</strong>
J. Med. Genet. 14: 200-204, 1977.
[PubMed: 881711]
[Full Text: https://doi.org/10.1136/jmg.14.3.200]
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Pope, F. M., Nicholls, A. C., Jones, P. M., Wells, R. S., Lawrence, D.
<strong>EDS IV (acrogeria): new autosomal dominant and recessive types.</strong>
J. Roy. Soc. Med. 73: 180-186, 1980.
[PubMed: 7230200]
</p>
</li>
<li>
<p class="mim-text-font">
Pope, F. M., Nicholls, A. C.
<strong>Pregnancy and Ehlers-Danlos syndrome type IV. (Letter)</strong>
Lancet 321: 249-250, 1983. Note: Originally Volume I.
[PubMed: 6130287]
[Full Text: https://doi.org/10.1016/s0140-6736(83)92631-4]
</p>
</li>
<li>
<p class="mim-text-font">
Prontera, P., Belcastro, V., Calabresi, P., Donti, E.
<strong>Myostatin depletion: a therapy for Ehlers-Danlos syndrome?</strong>
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<li>
<p class="mim-text-font">
Richards, A. J., Ward, P. N., Narcisi, P., Nicholls, A. C., Lloyd, J. C., Pope, F. M.
<strong>A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV: an unaffected family member is mosaic for the mutation.</strong>
Hum. Genet. 89: 414-418, 1992.
[PubMed: 1352273]
[Full Text: https://doi.org/10.1007/BF00194313]
</p>
</li>
<li>
<p class="mim-text-font">
Roberts, D. L. L., Pope, F. M., Nicholls, A. C., Narcisi, P.
<strong>Ehlers-Danlos syndrome type IV mimicking non-accidental injury in a child.</strong>
Brit. J. Derm. 111: 341-345, 1984.
[PubMed: 6477831]
[Full Text: https://doi.org/10.1111/j.1365-2133.1984.tb04733.x]
</p>
</li>
<li>
<p class="mim-text-font">
Rudd, N. L., Nimrod, C., Holbrook, K. A., Byers, P. H.
<strong>Pregnancy complications in type IV Ehlers-Danlos syndrome.</strong>
Lancet 321: 50-53, 1983. Note: Originally Volume I.
[PubMed: 6129381]
[Full Text: https://doi.org/10.1016/s0140-6736(83)91577-5]
</p>
</li>
<li>
<p class="mim-text-font">
Schievink, W. I., Limburg, M.
<strong>Angiographic abnormalities mimicking fibromuscular dysplasia in a patient with Ehlers-Danlos syndrome, type IV. (Letter)</strong>
Neurosurgery 25: 482-483, 1989.
[PubMed: 2771024]
[Full Text: https://doi.org/10.1097/00006123-198909000-00033]
</p>
</li>
<li>
<p class="mim-text-font">
Schwartz, R. C., Byers, P. H., Chu, M.-L., Weil, D., Ramirez, F., Tsipouras, P.
<strong>Ehlers-Danlos syndrome type IV (EDS IV): genetic linkage to the pro-alpha-1(III) collagen gene. (Abstract)</strong>
Am. J. Hum. Genet. 37: A173, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Schwarze, U., Schievink, W. I., Petty, E., Jaff, M. R., Babovic-Vuksanovic, D., Cherry, K. J., Pepin, M., Byers, P. H.
<strong>Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV.</strong>
Am. J. Hum. Genet. 69: 989-1001, 2001.
[PubMed: 11577371]
[Full Text: https://doi.org/10.1086/324123]
</p>
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<li>
<p class="mim-text-font">
Sherry, R. M., Fisch, A., Grey, D. P., Lubbock, C. A.
<strong>Embolization of a hepatoportal fistula in a patient with Ehlers-Danlos syndrome and colon perforation.</strong>
Surgery 111: 475-478, 1992.
[PubMed: 1557695]
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B., Superti-Furga, A., Joller-Jemelka, H. I., Cetta, G., Byers, P. H.
<strong>Ehlers-Danlos syndrome type IV--a subset of patients distinguished by low serum levels of the amino-terminal propeptide of type III procollagen.</strong>
Am. J. Med. Genet. 34: 68-71, 1989.
[PubMed: 2816989]
[Full Text: https://doi.org/10.1002/ajmg.1320340113]
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Gugler, E., Gitzelmann, R., Steinmann, B.
<strong>Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen.</strong>
J. Biol. Chem. 263: 6226-6232, 1988.
[PubMed: 2834369]
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Royce, P. M., Gugler, E., Gitzelmann, R., Steinmann, B.
<strong>A structural defect of type III collagen causing Ehlers-Danlos syndrome type IV. (Abstract)</strong>
Pediat. Res. 20: 1043, 1986.
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Saesseli, B., Steinmann, B., Bollinger, A.
<strong>Microangiopathy in Ehlers-Danlos syndrome type IV.</strong>
Int. J. Microcirc. Clin. Exp. 11: 241-247, 1992. Note: Erratum: Int. J. Microcirc. Clin. Exp. 11: 455 only, 1992.
[PubMed: 1506129]
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B., Ramirez, F., Byers, P. H.
<strong>Molecular defects of type III procollagen in Ehlers-Danlos syndrome type IV.</strong>
Hum. Genet. 82: 104-108, 1989.
[PubMed: 2722184]
[Full Text: https://doi.org/10.1007/BF00284038]
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B.
<strong>Impaired secretion of type III procollagen in Ehlers-Danlos syndrome type IV fibroblasts: correction of the defect by incubation at reduced temperature and demonstration of subtle alterations in the triple-helical region of the molecule.</strong>
Biochem. Biophys. Res. Commun. 150: 140-147, 1988.
[PubMed: 3337712]
[Full Text: https://doi.org/10.1016/0006-291x(88)90497-4]
</p>
</li>
<li>
<p class="mim-text-font">
Superti-Furga, A., Steinmann, B.
<strong>Ehlers-Danlos syndrome type IV: another temperature-dependent skin disorder? (Letter)</strong>
J. Am. Acad. Derm. 21: 323, 1989.
[PubMed: 2768588]
[Full Text: https://doi.org/10.1016/s0190-9622(89)70192-4]
</p>
</li>
<li>
<p class="mim-text-font">
Tsipouras, P., Byers, P. H., Schwartz, R. C., Chu, M.-L., Weil, D., Pepe, G., Cassidy, S. B., Ramirez, F.
<strong>Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen.</strong>
Hum. Genet. 74: 41-46, 1986.
[PubMed: 2875936]
[Full Text: https://doi.org/10.1007/BF00278783]
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<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.
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<p class="mim-text-font">
Yost, B. A., Vogelsang, J. P., Lie, J. T.
<strong>Fatal hemoptysis in Ehlers-Danlos syndrome: old malady with a new curse.</strong>
Chest 107: 1465-1467, 1995.
[PubMed: 7750352]
[Full Text: https://doi.org/10.1378/chest.107.5.1465]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
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Ada Hamosh - updated : 1/27/2015<br>Ada Hamosh - updated : 9/28/2012<br>Cassandra L. Kniffin - updated : 4/22/2011<br>Cassandra L. Kniffin - updated : 5/11/2010<br>Cassandra L. Kniffin - updated : 11/19/2009<br>Marla J. F. O&#x27;Neill - updated : 9/25/2009<br>Marla J. F. O&#x27;Neill - updated : 11/10/2005<br>Victor A. McKusick - updated : 8/24/2004<br>Victor A. McKusick - updated : 7/10/2003<br>Victor A. McKusick - updated : 4/22/2003<br>Deborah L. Stone - updated : 2/28/2002<br>Victor A. McKusick - updated : 9/27/2000<br>Victor A. McKusick - updated : 3/23/2000<br>Sonja A. Rasmussen - updated : 5/12/1999<br>Victor A. McKusick - updated : 8/24/1998<br>Victor A. McKusick - updated : 3/24/1998<br>Orest Hurko - updated : 3/7/1996
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Victor A. McKusick : 6/4/1986
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carol : 07/18/2019<br>carol : 03/05/2019<br>ckniffin : 03/04/2019<br>carol : 12/22/2017<br>carol : 12/21/2017<br>carol : 07/09/2016<br>carol : 5/17/2016<br>carol : 1/27/2015<br>carol : 9/5/2014<br>alopez : 10/2/2012<br>terry : 9/28/2012<br>terry : 6/20/2012<br>carol : 6/19/2012<br>carol : 5/30/2012<br>alopez : 1/20/2012<br>terry : 5/31/2011<br>wwang : 5/12/2011<br>ckniffin : 4/22/2011<br>carol : 8/13/2010<br>wwang : 5/13/2010<br>ckniffin : 5/11/2010<br>ckniffin : 5/11/2010<br>terry : 4/30/2010<br>wwang : 2/17/2010<br>carol : 1/21/2010<br>ckniffin : 11/19/2009<br>carol : 9/30/2009<br>carol : 9/28/2009<br>carol : 9/25/2009<br>terry : 1/13/2009<br>carol : 3/15/2007<br>alopez : 10/11/2006<br>terry : 9/20/2006<br>wwang : 11/10/2005<br>tkritzer : 9/2/2004<br>terry : 8/24/2004<br>carol : 12/3/2003<br>carol : 12/3/2003<br>tkritzer : 8/4/2003<br>tkritzer : 7/31/2003<br>terry : 7/10/2003<br>cwells : 4/28/2003<br>terry : 4/22/2003<br>carol : 4/4/2003<br>carol : 2/28/2002<br>mcapotos : 10/12/2000<br>mcapotos : 10/10/2000<br>terry : 9/27/2000<br>terry : 9/27/2000<br>carol : 8/1/2000<br>terry : 7/25/2000<br>mcapotos : 4/14/2000<br>mcapotos : 4/13/2000<br>terry : 3/23/2000<br>carol : 2/17/2000<br>carol : 5/12/1999<br>terry : 4/30/1999<br>carol : 11/15/1998<br>carol : 8/25/1998<br>terry : 8/24/1998<br>psherman : 3/24/1998<br>dholmes : 3/6/1998<br>mark : 5/15/1996<br>terry : 5/10/1996<br>terry : 4/15/1996<br>mark : 3/7/1996<br>terry : 2/23/1996<br>mark : 7/11/1995<br>pfoster : 1/17/1995<br>davew : 8/25/1994<br>carol : 5/13/1994<br>warfield : 4/8/1994<br>mimadm : 2/21/1994
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