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Entry
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- #153400 - LYMPHEDEMA-DISTICHIASIS SYNDROME; LPHDST
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- OMIM
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<p>
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<span class="h4">#153400</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/153400"><strong>Clinical Synopsis</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#mapping">Mapping</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</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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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=LYMPHEDEMA-DISTICHIASIS SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10305&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1457/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/lymphedema-distichiasis-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=153400[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33001" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/f9868902-97ed-4592-9bb5-8b8a24862f44/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0111509" 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>
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<div><a href="http://www.informatics.jax.org/disease/153400" 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>
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<div><a href="https://wormbase.org/resources/disease/DOID:0111509" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<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.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 8634009<br />
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<strong>ORPHA:</strong> 33001<br />
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<strong>DO:</strong> 0111509<br />
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">ICD+</a>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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153400
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
|
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<span class="mim-font">
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LYMPHEDEMA-DISTICHIASIS SYNDROME; LPHDST
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
LYMPHEDEMA WITH DISTICHIASIS
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
|
|
<span class="h3 mim-font">
|
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LYMPHEDEMA-DISTICHIASIS SYNDROME WITH RENAL DISEASE AND DIABETES MELLITUS, INCLUDED
|
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/16/717?start=-3&limit=10&highlight=717">
|
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16q24.1
|
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</a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Lymphedema-distichiasis syndrome with renal disease and diabetes mellitus
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/153400"> 153400 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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FOXC2
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/602402"> 602402 </a>
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/16/717?start=-3&limit=10&highlight=717">
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16q24.1
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Lymphedema-distichiasis syndrome
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/153400"> 153400 </a>
|
|
</span>
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</td>
|
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<td>
|
|
<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
FOXC2
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602402"> 602402 </a>
|
|
</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
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<a href="/clinicalSynopsis/153400" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
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<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
|
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<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/153400" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/153400" 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>
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|
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<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
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|
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<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>
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|
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|
|
|
|
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|
|
|
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|
|
<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> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Accessory eyelashes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835225&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835225</a>]</span><br /> -
|
|
Districhiasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45889003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45889003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0263483&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0263483</a>]</span><br /> -
|
|
Corneal irritation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1112489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1112489</a>]</span><br /> -
|
|
Corneal ulceration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91514001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91514001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H16.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H16.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H16.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/370.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">370.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/370.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">370.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010043&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010043</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012804" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012804</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012804" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012804</a>]</span><br /> -
|
|
Photophobia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409668002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409668002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246622003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246622003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000613" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000613</a>]</span><br /> -
|
|
Conjunctivitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9826008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9826008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H10</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H10.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H10.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/372.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">372.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009763</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000509</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000509</a>]</span><br /> -
|
|
Styes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397513003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397513003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1489008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1489008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H00.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H00.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019917</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010606" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010606</a>]</span><br /> -
|
|
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cleft lip (4%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80281008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80281008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008924</a>, <a href="https://bioportal.bioontology.org/search?q=C4321245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4321245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000204" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000204</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span><br /> -
|
|
Cleft palate (4%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
|
</div>
|
|
|
|
</div>
|
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|
|
<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">
|
|
|
|
- Congenital heart defects (7%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13213009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13213009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q24.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span><br /> -
|
|
Tetralogy of Fallot <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86299006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86299006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0039685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039685</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001636" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001636</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001636" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001636</a>]</span><br /> -
|
|
Ventricular septal defects <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
|
|
Arrhythmias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698247007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698247007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/427" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003811&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003811</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</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">
|
|
|
|
- Patent ductus arteriosus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83330001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83330001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q25.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q25.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/747.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">747.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001643" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001643</a>]</span><br /> -
|
|
Varicose veins <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128060009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128060009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399989005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399989005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12856003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12856003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I83.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I83.90</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042345&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042345</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002619" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002619</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002619" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002619</a>]</span><br />
|
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|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
</div>
|
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|
|
</div>
|
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|
|
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spine </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Spinal extradural cysts may occur <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835233</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nails </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Yellow nails (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45342007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45342007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/400211001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">400211001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L60.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L60.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221348&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221348</a>, <a href="https://bioportal.bioontology.org/search?q=C1768507&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1768507</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011367" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011367</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011367" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011367</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
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|
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</div>
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|
|
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</div>
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|
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|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Lymphedema, predominantly in the lower limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835228&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835228</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003550</a>]</span><br /> -
|
|
Cellulitis or infection may occur <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835231</a>]</span><br /> -
|
|
Lymphography shows increased number of dilated lymphatic vessels (hyperplasia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835232&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835232</a>]</span><br />
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|
|
</span>
|
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</div>
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</div>
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</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
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- Onset of lymphedema around puberty <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835229</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001004</a>]</span><br /> -
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- Caused by mutation in the forkhead box C2 gene (FOXC2, <a href="/entry/602402#0001">602402.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that the lymphedema-distichiasis syndrome (LPHDST) is caused by heterozygous mutation in the FOXC2 gene (<a href="/entry/602402">602402</a>) on chromosome 16q24.</p><p>See also lymphatic malformation-5 (LMPHM5; <a href="/entry/153200">153200</a>) and lymphedema and yellow nail syndrome (<a href="/entry/153300">153300</a>), which show phenotypic overlap.</p>
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<p>Lymphedema-distichiasis syndrome (LPHDST) is an autosomal dominant disorder that classically presents as lymphedema of the limbs and double rows of eyelashes (distichiasis). Irritation of the cornea, with corneal ulceration in some cases, brings the patients to the attention of ophthalmologists. Other complications may include cardiac defects, varicose veins, ptosis, cleft palate, spinal extradural cysts, and photophobia (<a href="#13" class="mim-tip-reference" title="Fang, J., Dagenais, S. L., Erickson, R. P., Arlt, M. F., Glynn, M. W., Gorski, J. L., Seaver, L. H., Glover, T. W. <strong>Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome.</strong> Am. J. Hum. Genet. 67: 1382-1388, 2000. Note: Erratum: Am. J. Hum. Genet. 68: 818 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11078474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11078474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11078474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11078474">Fang et al., 2000</a>; <a href="#4" class="mim-tip-reference" title="Brice, G., Mansour, S., Bell, R., Collin, J. R. O., Child, A. H., Brady, A. F., Sarfarazi, M., Burnand, K. G., Jeffery, S., Mortimer, P., Murday, V. A. <strong>Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.</strong> J. Med. Genet. 39: 478-483, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114478</a>] [<a href="https://doi.org/10.1136/jmg.39.7.478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114478">Brice et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11078474+12114478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a family reported by <a href="#3" class="mim-tip-reference" title="Bloom, D. <strong>Hereditary lymphedema (Nonne-Milroy-Meige). Report of a family with hereditary lymphedema associated with ptosis of the eyelids in several generations.</strong> New York J. Med. 41: 856-863, 1941."None>Bloom (1941)</a>, lymphedema of the legs occurred in 5 generations; six affected persons in 3 consecutive generations also had ptosis.</p><p>The first description of the combination of lymphedema and distichiasis was reported by <a href="#24" class="mim-tip-reference" title="Neel, J. V., Schull, W. J. <strong>Human Heredity.</strong> Chicago: Univ. of Chicago Press (pub.) 1954. Pp. 50-51."None>Neel and Schull (1954)</a>. <a href="#12" class="mim-tip-reference" title="Falls, H. F., Kertesz, E. D. <strong>A new syndrome combining pterygium colli with developmental anomalies of the eyelids and lymphatics of the lower extremities.</strong> Trans. Am. Ophthal. Soc. 62: 248-275, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14269895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14269895</a>]" pmid="14269895">Falls and Kertesz (1964)</a> reported 4 sibs with bilateral lymphedema of the legs and distichiasis. One of the 4 had striking webbed neck, whereas 2 were thought to have mild webbing. Several of the affected persons complained of photophobia and had partial ectropion of the lateral third of the lower lids, giving them a wide-eyed appearance. The father and one of his brothers reportedly had lymphedema, distichiasis, and webbed neck, and the paternal grandmother had lymphedema. An affected paternal uncle died of metastatic fibrosarcoma originating in an edematous leg. <a href="#12" class="mim-tip-reference" title="Falls, H. F., Kertesz, E. D. <strong>A new syndrome combining pterygium colli with developmental anomalies of the eyelids and lymphatics of the lower extremities.</strong> Trans. Am. Ophthal. Soc. 62: 248-275, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14269895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14269895</a>]" pmid="14269895">Falls and Kertesz (1964)</a> made brief reference to a second family in which the male proband had ptosis and lymphedema and the father ptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14269895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Chynn, K.-Y. <strong>Congenital spinal extradural cyst in two siblings.</strong> Am. J. Roentgen. Radium Ther. Nucl. Med. 101: 204-215, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6037336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6037336</a>] [<a href="https://doi.org/10.2214/ajr.101.1.204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6037336">Chynn (1967)</a> reported lymphedema and distichiasis with spinal extradural cyst (SEDAC) in 2 black sibs, aged 12 and 10 at the time of diagnosis. Progressive weakness in the legs was the main symptom. Another sib had lymphedema and distichiasis and may have had SEDAC. <a href="#2" class="mim-tip-reference" title="Bergland, R. M. <strong>Congenital intraspinal extradural cyst: report of three cases in one family.</strong> J. Neurosurg. 28: 495-499, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5659579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5659579</a>] [<a href="https://doi.org/10.3171/jns.1968.28.5.0495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5659579">Bergland (1968)</a> reported 3 of 4 sibs affected in the pedigree reported by <a href="#5" class="mim-tip-reference" title="Chynn, K.-Y. <strong>Congenital spinal extradural cyst in two siblings.</strong> Am. J. Roentgen. Radium Ther. Nucl. Med. 101: 204-215, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6037336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6037336</a>] [<a href="https://doi.org/10.2214/ajr.101.1.204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6037336">Chynn (1967)</a>. Spinal changes were present but asymptomatic in the affected father, daughter, and son described by <a href="#28" class="mim-tip-reference" title="Robinow, M., Johnson, G. F., Verhagen, A. D. <strong>Distichiasis-lymphedema: a hereditary syndrome of multiple congenital defects.</strong> Am. J. Dis. Child. 119: 343-347, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5434594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5434594</a>]" pmid="5434594">Robinow et al. (1970)</a>. <a href="#15" class="mim-tip-reference" title="Hoover, R. E. <strong>Personal Communication.</strong> Baltimore, Md. 1971."None>Hoover (1971)</a> studied a family with the lymphedema-distichiasis syndrome in 3 generations. <a href="#6" class="mim-tip-reference" title="Cilluffo, J. M., Gomez, M. R., Reese, D. F., Onofrio, B. M., Miller, R. H. <strong>Idiopathic ('congenital') spinal arachnoid diverticula: clinical diagnosis and surgical results.</strong> Mayo Clin. Proc. 56: 93-101, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6780735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6780735</a>]" pmid="6780735">Cilluffo et al. (1981)</a> noted that spinal extradural cysts are often arachnoid diverticula. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6780735+5434594+6037336+5659579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Dale, R. F. <strong>Primary lymphoedema when found with distichiasis is of the type defined as bilateral hyperplasia by lymphography.</strong> J. Med. Genet. 24: 170-171, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3573000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3573000</a>] [<a href="https://doi.org/10.1136/jmg.24.3.170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3573000">Dale (1987)</a> noted that 'bilateral hyperplasia' lymphedema is an uncommon form of lymphedema in which lymphography shows abundant, dilated lymphatics occurring in both lower limbs, and the thoracic duct is either absent, obstructed, or deformed. Further, he noted that this form of lymphedema is often associated with other congenital malformations, including distichiasis and congenital heart disease. In a survey of 725 patients with primary lymphedema treated at St. Thomas' Hospital, <a href="#8" class="mim-tip-reference" title="Dale, R. F. <strong>Primary lymphoedema when found with distichiasis is of the type defined as bilateral hyperplasia by lymphography.</strong> J. Med. Genet. 24: 170-171, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3573000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3573000</a>] [<a href="https://doi.org/10.1136/jmg.24.3.170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3573000">Dale (1987)</a> found 5 with distichiasis, all of whom showed bilateral hyperplasia. Of 475 patients investigated by lymphography, only 30 (6%) had bilateral hyperplasia. Of these, 11 (36%) had a positive family history, and 3 had both distichiasis and bilateral hyperplasia. Further examination of these affected families showed a variable phenotype, in that some members had both lymphedema and distichiasis, whereas others had only lymphedema. <a href="#18" class="mim-tip-reference" title="Kolin, T., Johns, K. J., Wadlington, W. B., Butler, M. G., Sunalp, M. A., Wright, K. W. <strong>Hereditary lymphedema and distichiasis.</strong> Arch. Ophthal. 109: 980-981, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2064580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2064580</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=2064580[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/archopht.1991.01080070092042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2064580">Kolin et al. (1991)</a> described 2 cases of distichiasis, one in association with familial and congenital lymphedema with hypoplasia of lymphatics (suggesting Milroy disease), and the second in association with pubertal onset of lymphedema. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3573000+2064580" 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="#17" class="mim-tip-reference" title="Johnson, S. M., Kincannon, J. M., Horn, T. D. <strong>Lymphedema-distichiasis syndrome: report of a case and review. (Letter)</strong> Arch. Derm. 135: 347-348, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10086462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10086462</a>] [<a href="https://doi.org/10.1001/archderm.135.3.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10086462">Johnson et al. (1999)</a> described this syndrome in a 14-year-old African American girl who presented with a 3-month history of nonpitting edema beginning on the left distal leg and progressing to both lower extremities and extending to the thigh. She had had surgery for dual-chamber pacemaker placement for symptomatic bradycardia due to Mobitz type I secondary atrioventricular block and correction of supracardiac total anomalous pulmonary venous connection and patent ductus arteriosus (see <a href="/entry/607411">607411</a>). The family history was notable for a maternal grandmother and a great-grandmother with lymphedema and congenital heart disease; the medical condition of the mother of the proband was unknown. Ophthalmic examination showed a bilateral double row of eyelashes without corneal abrasion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10086462" 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="Finegold, D. N., Kimak, M. A., Lawrence, E. C., Levinson, K. L., Cherniske, E. M., Pober, B. R., Dunlap, J. W., Ferrell, R. E. <strong>Truncating mutations in FOXC2 cause multiple lymphedema syndromes.</strong> Hum. Molec. Genet. 10: 1185-1189, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371511</a>] [<a href="https://doi.org/10.1093/hmg/10.11.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11371511">Finegold et al. (2001)</a> studied 11 families with lymphedema and mutations in the FOXC2 gene. Broad phenotypic heterogeneity was observed within the families, as well as overlapping phenotypically defined lymphedema syndromes: Meige lymphedema (LMPHM5; <a href="/entry/153200">153200</a>), lymphedema-distichiasis syndrome, and yellow nail syndrome (<a href="/entry/153300">153300</a>), but not Milroy disease (LMPHM1; <a href="/entry/153100">153100</a>). The authors stated that the phenotypic classification of autosomal dominant lymphedema did not appear to reflect the underlying genetic causation of these disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11371511" 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="#4" class="mim-tip-reference" title="Brice, G., Mansour, S., Bell, R., Collin, J. R. O., Child, A. H., Brady, A. F., Sarfarazi, M., Burnand, K. G., Jeffery, S., Mortimer, P., Murday, V. A. <strong>Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.</strong> J. Med. Genet. 39: 478-483, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114478</a>] [<a href="https://doi.org/10.1136/jmg.39.7.478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114478">Brice et al. (2002)</a> described in detail the clinical findings in 74 affected subjects from 18 families, as well as 6 isolated cases, with the lymphedema-distichiasis syndrome. All patients had mutations in the FOXC2 gene, except 2 affected brothers who showed linkage to the FOXC2 gene. Fifty-seven of the 74 patients had clinical evidence of lymphedema, with the onset in males (9 to 11 years) significantly earlier than the onset in females (14 to 20 years), but penetrance appeared complete in both sexes by the age of 40 years. The lymphedema was usually bilateral and asymmetric. Lymphoscintigram in 9 patients showed abnormally low uptake of radioactive colloid in inguinal nodes, increased number of lymph conducting pathways, and lymph reflux. Distichiasis occurred in 94% of patients, 74% of whom had complications, including corneal irritation, photophobia, conjunctivitis, and styes. Ptosis was noted in 31%, congenital heart disease in 6.8%, and cleft palate in 4%. No patients had spinal extradural cysts. Five patients had renal abnormalities, including nephritis, duplex kidney, and recurrent infections. Varicose veins were present in 49% and were notable for early onset and increased prevalence compared to the general population, and <a href="#4" class="mim-tip-reference" title="Brice, G., Mansour, S., Bell, R., Collin, J. R. O., Child, A. H., Brady, A. F., Sarfarazi, M., Burnand, K. G., Jeffery, S., Mortimer, P., Murday, V. A. <strong>Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.</strong> J. Med. Genet. 39: 478-483, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114478</a>] [<a href="https://doi.org/10.1136/jmg.39.7.478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114478">Brice et al. (2002)</a> emphasized the link between the lymphatic and vascular systems being affected. There were no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12114478" 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="#26" class="mim-tip-reference" title="Patil, B. B., Bell, R., Brice, G., Jeffery, S., Dessai, S. P. <strong>Distichiasis without lymphedema?</strong> Eye 18: 1270-1272, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044942</a>] [<a href="https://doi.org/10.1038/sj.eye.6701387" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044942">Patil et al. (2004)</a> noted that distichiasis is the most consistent feature of lymphedema-distichiasis syndrome and made observations on distichiasis without lymphedema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15044942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Yildirim-Toruner, C., Subramanian, K., El Manjra, L., Chen, E., Goldstein, S., Vitale, E. <strong>A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.</strong> Am. J. Med. Genet. 131A: 281-286, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523639</a>] [<a href="https://doi.org/10.1002/ajmg.a.30390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523639">Yildirim-Toruner et al. (2004)</a> reported a German-Irish family in which 6 affected members spanning 3 generations had lymphedema-distichiasis syndrome. Four of the affected members also had renal disease, and 3 had type II diabetes mellitus (see <a href="/entry/125853">125853</a>), features not usually seen in lymphedema-distichiasis syndrome. The oldest affected member of the family was 73 years old at the time of report and was on chronic renal dialysis. One of her sons, aged 45 years, had developed proteinuria at age 32 years. Renal biopsy showed chronic sclerosing glomerulopathy and chronic tubulointerstitial nephritis. One member of the family underwent renal transplantation and, shortly thereafter, pancreatic transplantation, both with excellent results. She was 36 years old at the time of report and had distichiasis but no lymphedema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523639" 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="#33" class="mim-tip-reference" title="Yabuki, S., Kikuchi, S., Ikegawa, S. <strong>Spinal extradural arachnoid cysts associated with distichiasis and lymphedema.</strong> Am. J. Med. Genet. 143A: 884-887, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17366583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17366583</a>] [<a href="https://doi.org/10.1002/ajmg.a.31669" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17366583">Yabuki et al. (2007)</a> reported a Japanese family in which 10 members had variable manifestations of lymphedema-distichiasis syndrome. Spinal extradural arachnoid cysts (SEDAC) were found in 7 patients, of whom 4 had distichiasis. Two patients had isolated distichiasis, and 1 had lymphedema and distichiasis. Only 1 individual had all 3 features. Inheritance was clearly autosomal dominant. Although genetic analysis of the FOXC2 gene was not performed, the clinical features were suggestive of the diagnosis and indicated that SEDAC may be a common component. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17366583" 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="#20" class="mim-tip-reference" title="Kumar, S., Carver, C., McCall, S., Brice, G., Ostergaard, P., Mortimer, P., Jeffery, S., Lymphoedema Consortium. <strong>A family with lymphoedema-distichiasis where identical twins have a discordant phenotype. (Letter)</strong> Clin. Genet. 71: 285-287, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17309653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17309653</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00758.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17309653">Kumar et al. (2007)</a> reported a 3-generation family from Jordan in which 12 members had lymphedema-distichiasis; 10 were alive at the time of the study, including a pair of affected identical twins who were discordant for the phenotype, as only 1 had lymphedema and varicose veins at age 28 years. The findings suggested that phenotypic variation in the disorder is not always due to modifying genes. All affected individuals had distichiasis, 5 had lymphedema, 4 had varicose veins, and 3 had cleft palate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17309653" 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="#22" class="mim-tip-reference" title="Mellor, R. H., Brice, G., Stanton, A. W. B., French, J., Smith, A., Jeffery, S., Levick, J. R., Burnand, K. G., Mortimer, P. S. <strong>Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb.</strong> Circulation 115: 1912-1920, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17372167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17372167</a>] [<a href="https://doi.org/10.1161/CIRCULATIONAHA.106.675348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17372167">Mellor et al. (2007)</a> examined the venous system of the leg with Duplex ultrasound in 18 FOXC2 mutation-positive individuals, including 3 without lymphedema, from 7 families with lymphedema-distichiasis syndrome previously reported by <a href="#1" class="mim-tip-reference" title="Bell, R., Brice, G., Child, A. H., Murday, V. A., Mansour, S., Sandy, C. J., Collin, J. R. O., Brady, A. F., Callen, D. F., Burnand, K., Mortimer, P., Jeffery, S. <strong>Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene.</strong> Hum. Genet. 108: 546-551, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11499682/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11499682</a>] [<a href="https://doi.org/10.1007/s004390100528" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11499682">Bell et al. (2001)</a> and <a href="#4" class="mim-tip-reference" title="Brice, G., Mansour, S., Bell, R., Collin, J. R. O., Child, A. H., Brady, A. F., Sarfarazi, M., Burnand, K. G., Jeffery, S., Mortimer, P., Murday, V. A. <strong>Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.</strong> J. Med. Genet. 39: 478-483, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114478</a>] [<a href="https://doi.org/10.1136/jmg.39.7.478" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114478">Brice et al. (2002)</a>. All 18 had superficial venous reflux in the great saphenous vein, compared to only 1 of 12 controls (10 of whom were mutation-negative family members). Deep venous reflux was also recorded in 14 of the 18 mutation-positive individuals, including all 3 mutation carriers without lymphedema, compared to only 1 of 12 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12114478+11499682+17372167" 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="#27" class="mim-tip-reference" title="Rezaie, T., Ghoroghchian, R., Bell, R., Brice, G., Hasan, A., Burnand, K., Vernon, S., Mansour, S., Mortimer, P., Jeffery, S., Child, A., Sarfarazi, M. <strong>Primary non-syndromic lymphoedema (Meige disease) is not caused by mutations in FOXC2.</strong> Europ. J. Hum. Genet. 16: 300-304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18197197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18197197</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18197197">Rezaie et al. (2008)</a> disputed the clinical diagnoses of some of the patients reported by <a href="#14" class="mim-tip-reference" title="Finegold, D. N., Kimak, M. A., Lawrence, E. C., Levinson, K. L., Cherniske, E. M., Pober, B. R., Dunlap, J. W., Ferrell, R. E. <strong>Truncating mutations in FOXC2 cause multiple lymphedema syndromes.</strong> Hum. Molec. Genet. 10: 1185-1189, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371511</a>] [<a href="https://doi.org/10.1093/hmg/10.11.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11371511">Finegold et al. (2001)</a>. In particular, 10 of the 11 families reported by <a href="#14" class="mim-tip-reference" title="Finegold, D. N., Kimak, M. A., Lawrence, E. C., Levinson, K. L., Cherniske, E. M., Pober, B. R., Dunlap, J. W., Ferrell, R. E. <strong>Truncating mutations in FOXC2 cause multiple lymphedema syndromes.</strong> Hum. Molec. Genet. 10: 1185-1189, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371511</a>] [<a href="https://doi.org/10.1093/hmg/10.11.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11371511">Finegold et al. (2001)</a> had distichiasis, consistent with the lymphedema-distichiasis syndrome. The last family was not reported to have either yellow nails or distichiasis, but <a href="#27" class="mim-tip-reference" title="Rezaie, T., Ghoroghchian, R., Bell, R., Brice, G., Hasan, A., Burnand, K., Vernon, S., Mansour, S., Mortimer, P., Jeffery, S., Child, A., Sarfarazi, M. <strong>Primary non-syndromic lymphoedema (Meige disease) is not caused by mutations in FOXC2.</strong> Europ. J. Hum. Genet. 16: 300-304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18197197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18197197</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18197197">Rezaie et al. (2008)</a> emphasized that the detection of distichiasis is often difficult to confirm and cannot be assumed to be absent from patient self-reports. In addition, <a href="#27" class="mim-tip-reference" title="Rezaie, T., Ghoroghchian, R., Bell, R., Brice, G., Hasan, A., Burnand, K., Vernon, S., Mansour, S., Mortimer, P., Jeffery, S., Child, A., Sarfarazi, M. <strong>Primary non-syndromic lymphoedema (Meige disease) is not caused by mutations in FOXC2.</strong> Europ. J. Hum. Genet. 16: 300-304, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18197197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18197197</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201982" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18197197">Rezaie et al. (2008)</a> did not identify mutations in the FOXC2 gene in 22 unrelated probands with Meige disease, i.e., lymphedema without distichiasis. One additional proband was found to carry a FOXC2 mutation, but detailed ophthalmologic examination revealed accessory eyelashes in him and his affected family members, thus confirming the diagnosis of lymphedema-distichiasis. The authors also noted that ptosis is a variable feature of the lymphedema-distichiasis syndrome, occurring in about 30% of patients, and suggested that lymphedema and ptosis alone do not comprise a distinct syndrome; rather, those patients likely also have distichiasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18197197+11371511" 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>From a cohort of 288 patients with primary noncongenital lymphedema, <a href="#31" class="mim-tip-reference" title="van Steensel, M. A. M., Damstra, R. J., Heitink, M. V., Bladergroen, R. S., Veraart, J., Steijlen, P. M., van Geel, M. <strong>Novel missense mutations in the FOXC2 gene alter transcriptional activity.</strong> Hum. Mutat. 30: E1002-E1009, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19760751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19760751</a>] [<a href="https://doi.org/10.1002/humu.21127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19760751">van Steensel et al. (2009)</a> reported 11 probands who were heterozygous for mutations in the FOXC2 gene. Seven of the probands had a positive family history for lymphedema, but family members were not available for study. All 11 patients had venous insufficiency, which affected the deep system in 8. Only 2 patients were reported to have distichiasis, but the authors noted that it is a feature that can be quite subtle and might have been missed. Lymphoscintigraphy performed in 1 patient with a gain-of-function missense mutation (see <a href="/entry/602402#0016">602402.0016</a>) showed minimal uptake (0.5% on the right and 1.7% on the left), indicating lack of transport consistent with lymphatic hypoplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19760751" 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="De Niear, M. A., Breazzano, M. P., Mawn, L. A. <strong>Novel FOXC2 mutation and distichiasis in a patient with lymphedema-distichiasis syndrome.</strong> Ophthalmic Plast. Reconst. Surg. 34: e88-e90, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29406328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29406328</a>] [<a href="https://doi.org/10.1097/IOP.0000000000001079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29406328">De Niear et al. (2018)</a> reported a 3-generation family with lymphedema-distichiasis. The proband was a 4-year-old boy who presented with distichiasis and photophobia, eye rubbing, and squinting, but did not exhibit lymphedema. Examination showed that the lashes originated from the meibomian gland orifices of all 4 lids. Family history revealed that the proband's mother had distichiasis with onset of lymphedema at age 12 as well as ptosis and varicose veins. His maternal grandmother was also reported to have had lymphedema, distichiasis, and varicose veins. In addition, family pedigree showed an affected brother with distichiasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29406328" 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 3 families with lymphedema-distichiasis, <a href="#21" class="mim-tip-reference" title="Mangion, J., Rahman, N., Mansour, S., Brice, G., Rosbotham, J., Child, A. H., Murday, V. A., Mortimer, P. S., Barfoot, R., Sigurdsson, A., Edkins, S., Sarfarazi, M., Burnand, K., Evans, A. L., Nunan, T. O., Stratton, M. R., Jeffery, S. <strong>A gene for lymphedema-distichiasis maps to 16q24.3.</strong> Am. J. Hum. Genet. 65: 427-432, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417285</a>] [<a href="https://doi.org/10.1086/302500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10417285">Mangion et al. (1999)</a> found linkage to 16q24.3. Subsequent analysis of the region for recombinants placed the locus between D16S422 and D16S3074, a distance of approximately 16 cM. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Erickson, R. P., Hudgins, L., Stone, J. F., Schmidt, S., Wilke, C., Glover, T. W. <strong>A 'balanced' Y;16 translocation associated with Turner-like neonatal lymphedema suggests the location of a potential anti-Turner gene on the Y chromosome.</strong> Cytogenet. Cell Genet. 71: 163-167, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7656589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7656589</a>] [<a href="https://doi.org/10.1159/000134099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7656589">Erickson et al. (1995)</a> described neonatal lymphedema, similar to that seen in Turner syndrome, associated with a Y;16 translocation in a male infant. They were not able to find a candidate gene on the Y chromosome to account for the lymphedema and turned their attention to the breakpoint in chromosome 16 at 16q24.3. When the lymphedema-distichiasis syndrome was mapped to a 16-cM region on distal chromosome 16, they determined that the breakpoint in the Y;16 translocation was within this region and narrowed the region to a 20-kb segment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7656589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of LPHDST in the families reported by <a href="#13" class="mim-tip-reference" title="Fang, J., Dagenais, S. L., Erickson, R. P., Arlt, M. F., Glynn, M. W., Gorski, J. L., Seaver, L. H., Glover, T. W. <strong>Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome.</strong> Am. J. Hum. Genet. 67: 1382-1388, 2000. Note: Erratum: Am. J. Hum. Genet. 68: 818 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11078474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11078474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11078474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11078474">Fang et al. (2000)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11078474" 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 2 families with autosomal dominant lymphedema-distichiasis syndrome, <a href="#13" class="mim-tip-reference" title="Fang, J., Dagenais, S. L., Erickson, R. P., Arlt, M. F., Glynn, M. W., Gorski, J. L., Seaver, L. H., Glover, T. W. <strong>Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome.</strong> Am. J. Hum. Genet. 67: 1382-1388, 2000. Note: Erratum: Am. J. Hum. Genet. 68: 818 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11078474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11078474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11078474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11078474">Fang et al. (2000)</a> identified heterozygous inactivating mutations in the FOXC2 gene: a nonsense mutation (<a href="/entry/602402#0001">602402.0001</a>) and a frameshift mutation (<a href="/entry/602402#0002">602402.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11078474" 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 with lymphedema-distichiasis syndrome originally reported by <a href="#12" class="mim-tip-reference" title="Falls, H. F., Kertesz, E. D. <strong>A new syndrome combining pterygium colli with developmental anomalies of the eyelids and lymphatics of the lower extremities.</strong> Trans. Am. Ophthal. Soc. 62: 248-275, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14269895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14269895</a>]" pmid="14269895">Falls and Kertesz (1964)</a>, <a href="#10" class="mim-tip-reference" title="Erickson, R. P., Dagenais, S. L., Caulder, M. S., Downs, C. A., Herman, G., Jones, M. C., Kerstjens-Frederikse, W. S., Lidral, A. C., McDonald, M., Nelson, C. C., Witte, M., Glover, T. W. <strong>Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations.</strong> J. Med. Genet. 38: 761-766, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11694548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11694548</a>] [<a href="https://doi.org/10.1136/jmg.38.11.761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11694548">Erickson et al. (2001)</a> identified a heterozygous insertion/deletion mutation in the FOXC2 gene (<a href="/entry/602402#0011">602402.0011</a>), resulting in premature termination. <a href="#10" class="mim-tip-reference" title="Erickson, R. P., Dagenais, S. L., Caulder, M. S., Downs, C. A., Herman, G., Jones, M. C., Kerstjens-Frederikse, W. S., Lidral, A. C., McDonald, M., Nelson, C. C., Witte, M., Glover, T. W. <strong>Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations.</strong> J. Med. Genet. 38: 761-766, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11694548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11694548</a>] [<a href="https://doi.org/10.1136/jmg.38.11.761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11694548">Erickson et al. (2001)</a> described truncating mutations in the FOXC2 gene in 8 additional families with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14269895+11694548" 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="Finegold, D. N., Kimak, M. A., Lawrence, E. C., Levinson, K. L., Cherniske, E. M., Pober, B. R., Dunlap, J. W., Ferrell, R. E. <strong>Truncating mutations in FOXC2 cause multiple lymphedema syndromes.</strong> Hum. Molec. Genet. 10: 1185-1189, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11371511/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11371511</a>] [<a href="https://doi.org/10.1093/hmg/10.11.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11371511">Finegold et al. (2001)</a> identified mutations in the FOXC2 gene in 11 of 86 families with lymphedema-distichiasis syndrome (see, e.g., <a href="/entry/602402#0007">602402.0007</a> and <a href="/entry/602402#0008">602402.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11371511" 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 6 affected members spanning 3 generations of a German-Irish family with lymphedema-distichiasis syndrome, <a href="#34" class="mim-tip-reference" title="Yildirim-Toruner, C., Subramanian, K., El Manjra, L., Chen, E., Goldstein, S., Vitale, E. <strong>A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.</strong> Am. J. Med. Genet. 131A: 281-286, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523639</a>] [<a href="https://doi.org/10.1002/ajmg.a.30390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523639">Yildirim-Toruner et al. (2004)</a> identified a 1-bp insertion in the FOXC2 gene (<a href="/entry/602402#0010">602402.0010</a>). Affected individuals in this family also had renal disease and diabetes mellitus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523639" 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="van Steensel, M. A. M., Damstra, R. J., Heitink, M. V., Bladergroen, R. S., Veraart, J., Steijlen, P. M., van Geel, M. <strong>Novel missense mutations in the FOXC2 gene alter transcriptional activity.</strong> Hum. Mutat. 30: E1002-E1009, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19760751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19760751</a>] [<a href="https://doi.org/10.1002/humu.21127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19760751">Van Steensel et al. (2009)</a> screened a cohort of 288 patients with primary noncongenital lymphedema for mutations in the FLT4 (<a href="/entry/136352">136352</a>), SOX18 (<a href="/entry/601618">601618</a>), and FOXC2 genes, and identified 4 mutations in FLT4 (see LMPHM1, <a href="/entry/153100">153100</a>) and 11 in FOXC2. None of the FOXC2 variants were found in 100 unrelated Dutch controls or in the dbSNP (build 130) database, and all involved highly conserved residues. Five of the FOXC2 changes were predicted to truncate the protein, and 6 were missense mutations. Two of the missense mutations were located within the forkhead DNA-binding domain, including the previously reported S125L mutation (<a href="/entry/602402#0012">602402.0012</a>) and an R121C substitution (<a href="/entry/602402#0014">602402.0014</a>), whereas the remaining 4 occurred outside the forkhead domain (see, e.g., <a href="/entry/602402#0015">602402.0015</a> and <a href="/entry/602402#0016">602402.0016</a>). Functional analysis in HeLa Ohio and COS-7 cells showed that all 4 FOXC2 missense mutation outside the forkhead domain increased transcriptional and transactivation activity, whereas the missense mutations within the forkhead domain showed reduced activity. No genotype/phenotype correlations were observed. The authors concluded that gain-of-function mutations in FOXC2 can also cause lymphedema. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19760751" 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="Michelini, S., Degiorgio, D., Cestari, M., Corda, D., Ricci, M., Cardone, M., Mander, A., Famoso, L., Contini, E., Serrani, R., Pinelli, L., Cecchin, S., Bertelli, M. <strong>Clinical and genetic study of 46 Italian patients with primary lymphedema.</strong> Lymphology 45: 3-12, 2012. Note: Erratum: Lymphology 45: 87-88, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22768468/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22768468</a>]" pmid="22768468">Michelini et al. (2012)</a> screened the FLT4 and FOXC2 genes in a cohort of 46 Italian probands with primary lymphedema and identified FLT4 mutations in 6 (13%) and FOXC2 mutations in 6 (13%; see, e.g., <a href="/entry/602402#0017">602402.0017</a>). <a href="#30" class="mim-tip-reference" title="Tavian, D., Missaglia, S., Maltese, P. E., Michelini, S., Fiorentino, A., Ricci, M., Serrani, R., Walter, M. A., Bertelli, M. <strong>FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function.</strong> Oncotarget 7: 54228-54239, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27276711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27276711</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27276711[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.18632/oncotarget.9797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27276711">Tavian et al. (2016)</a> restudied the 6 Italian probands with FOXC2-associated lymphedema, 4 of whom had distichiasis upon slit-lamp examination. Consistent with previous reports, the 3 patients with activating mutations showed lymphatic hypoplasia on scintigraphy, whereas the 3 patients with inactivating mutations showed hyperplasia, suggesting a genotype/phenotype correlation. The authors stated that the association between FOXC2 function and distichiasis was less clear: all 3 patients with activating mutations had distichiasis, whereas it was present in only 1 of the 3 patients with inactivating mutations; they suggested that further studies were required to elucidate these correlations. <a href="#30" class="mim-tip-reference" title="Tavian, D., Missaglia, S., Maltese, P. E., Michelini, S., Fiorentino, A., Ricci, M., Serrani, R., Walter, M. A., Bertelli, M. <strong>FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function.</strong> Oncotarget 7: 54228-54239, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27276711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27276711</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27276711[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.18632/oncotarget.9797" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27276711">Tavian et al. (2016)</a> concluded that either complete loss or significant gain of FOXC2 function can cause a perturbation of lymphatic vessel formation resulting in lymphedema. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22768468+27276711" 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 the proband from a 3-generation family with lymphedema-distichiasis, <a href="#9" class="mim-tip-reference" title="De Niear, M. A., Breazzano, M. P., Mawn, L. A. <strong>Novel FOXC2 mutation and distichiasis in a patient with lymphedema-distichiasis syndrome.</strong> Ophthalmic Plast. Reconst. Surg. 34: e88-e90, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29406328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29406328</a>] [<a href="https://doi.org/10.1097/IOP.0000000000001079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29406328">De Niear et al. (2018)</a> identified heterozygosity for a 2-bp insertion in the FOXC2 gene that was not found in his unaffected brother. Mutation analysis of 4 other affected family members was not done. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29406328" 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="#19" class="mim-tip-reference" title="Kriederman, B. M., Myloyde, T. L., Witte, M. H., Dagenais, S. L., Witte, C. L., Rennels, M., Bernas, M. J., Lynch, M. T., Erickson, R. P., Caulder, M. S., Miura, N., Jackson, D., Brooks, B. P., Glover, T. W. <strong>FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.</strong> Hum. Molec. Genet. 12: 1179-1185, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719382</a>] [<a href="https://doi.org/10.1093/hmg/ddg123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719382">Kriederman et al. (2003)</a> performed dynamic lymphatic imaging and immunohistochemical examination of lymphatic tissues in mice heterozygous for a targeted disruption of Foxc2. Adult heterozygous mice characteristically exhibited a generalized lymphatic vessel and lymph node hyperplasia and rarely exhibited hindlimb swelling. Retrograde lymph flow through apparently incompetent interlymphangion valves into the mesenteric nodes, intestinal wall, and liver was also observed. In addition, Foxc2 heterozygous mice uniformly displayed distichiasis. <a href="#19" class="mim-tip-reference" title="Kriederman, B. M., Myloyde, T. L., Witte, M. H., Dagenais, S. L., Witte, C. L., Rennels, M., Bernas, M. J., Lynch, M. T., Erickson, R. P., Caulder, M. S., Miura, N., Jackson, D., Brooks, B. P., Glover, T. W. <strong>FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.</strong> Hum. Molec. Genet. 12: 1179-1185, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719382/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719382</a>] [<a href="https://doi.org/10.1093/hmg/ddg123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719382">Kriederman et al. (2003)</a> noted that the craniofacial, cardiovascular, and skeletal abnormalities sometimes associated with lymphedema-distichiasis syndrome had previously been shown to be fully penetrant in homozygous Foxc2-null mice (<a href="#16" class="mim-tip-reference" title="Iida, K., Koseki, H., Kakinuma, H., Kato, N., Mizutani-Koseki, Y., Ohucki, H., Yoshioka, H., Noji, S., Kawamura, K., Kataoka, Y., Ueno, F., Taniguchi, M., Yoshida, N., Sugiyama, T., Miura, N. <strong>Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis.</strong> Development 124: 4627-4638, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9409679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9409679</a>] [<a href="https://doi.org/10.1242/dev.124.22.4627" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9409679">Iida et al., 1997</a>; <a href="#32" class="mim-tip-reference" title="Winnier, G. E., Hargett, L., Hogan, B. L. M. <strong>The winged helix transcription factor MFH1 is required for proliferation and patterning of paraxial mesoderm in the mouse embryo.</strong> Genes Dev. 11: 926-940, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106663</a>] [<a href="https://doi.org/10.1101/gad.11.7.926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9106663">Winnier et al., 1997</a>). They concluded that Foxc2 haploinsufficient mice mimic closely the distinctive lymphatic and ocular phenotype of patients with lymphedema-distichiasis syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9106663+12719382+9409679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Corbett1982" class="mim-tip-reference" title="Corbett, C. R. R., Dale, R. F., Coltart, D. J., Kinmonth, J. B. <strong>Congenital heart disease in patients with primary lymphoedemas.</strong> Lymphology 15: 85-90, 1982.">Corbett et al. (1982)</a>; <a href="#Pap1980" class="mim-tip-reference" title="Pap, Z., Biro, T., Szabo, L., Papp, Z. <strong>Syndrome of lymphoedema and distichiasis.</strong> Hum. Genet. 53: 309-310, 1980.">Pap et al. (1980)</a>; <a href="#Schwartz1980" class="mim-tip-reference" title="Schwartz, J. F., O'Brien, M. S., Hoffman, J. C., Jr. <strong>Hereditary spinal arachnoid cysts, distichiasis, and lymphedema.</strong> Ann. Neurol. 7: 340-343, 1980.">Schwartz et al. (1980)</a>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.3171/jns.1968.28.5.0495" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.39.7.478" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.2214/ajr.101.1.204" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.24.3.170" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/IOP.0000000000001079" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.38.11.761" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/316915" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archderm.135.3.347" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 01/02/2019
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Marla J. F. O'Neill - updated : 7/10/2008<br>Cassandra L. Kniffin - updated : 8/29/2007<br>Cassandra L. Kniffin - updated : 5/17/2007<br>George E. Tiller - updated : 2/25/2005<br>Victor A. McKusick - updated : 1/21/2005<br>Cassandra L. Kniffin - reorganized : 11/19/2003<br>Cassandra L. Kniffin - updated : 11/12/2003<br>Michael J. Wright - updated : 10/22/2002<br>Victor A. McKusick - updated : 12/12/2000<br>Victor A. McKusick - updated : 1/11/2000<br>Victor A. McKusick - updated : 6/3/1999
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Victor A. McKusick : 6/2/1986
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carol : 07/13/2023
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carol : 05/16/2019<br>carol : 01/10/2019<br>carol : 01/02/2019<br>carol : 12/19/2018<br>carol : 08/17/2016<br>carol : 03/09/2015<br>alopez : 12/9/2014<br>carol : 9/16/2013<br>carol : 7/10/2008<br>ckniffin : 6/16/2008<br>wwang : 6/10/2008<br>ckniffin : 5/30/2008<br>wwang : 9/10/2007<br>ckniffin : 8/29/2007<br>wwang : 6/11/2007<br>ckniffin : 5/17/2007<br>terry : 9/27/2005<br>tkritzer : 3/7/2005<br>terry : 2/25/2005<br>carol : 1/21/2005<br>carol : 11/19/2003<br>ckniffin : 11/12/2003<br>mgross : 12/10/2002<br>tkritzer : 10/23/2002<br>terry : 10/22/2002<br>mcapotos : 12/21/2001<br>carol : 2/8/2001<br>mcapotos : 1/30/2001<br>mcapotos : 1/8/2001<br>mcapotos : 12/20/2000<br>mcapotos : 12/20/2000<br>terry : 12/12/2000<br>terry : 2/28/2000<br>mgross : 2/4/2000<br>terry : 1/11/2000<br>carol : 6/15/1999<br>carol : 6/15/1999<br>jlewis : 6/15/1999<br>terry : 6/3/1999<br>mimadm : 11/6/1994<br>warfield : 3/1/1994<br>supermim : 3/16/1992<br>carol : 9/30/1991<br>carol : 9/16/1991<br>supermim : 3/20/1990
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<strong>#</strong> 153400
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LYMPHEDEMA-DISTICHIASIS SYNDROME; LPHDST
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LYMPHEDEMA WITH DISTICHIASIS
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Other entities represented in this entry:
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LYMPHEDEMA-DISTICHIASIS SYNDROME WITH RENAL DISEASE AND DIABETES MELLITUS, INCLUDED
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<strong>SNOMEDCT:</strong> 8634009;
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<strong>ORPHA:</strong> 33001;
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<strong>DO:</strong> 0111509;
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Phenotype
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Inheritance
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16q24.1
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Lymphedema-distichiasis syndrome with renal disease and diabetes mellitus
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153400
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Autosomal dominant
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FOXC2
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16q24.1
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Lymphedema-distichiasis syndrome
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153400
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Autosomal dominant
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602402
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<p>A number sign (#) is used with this entry because of evidence that the lymphedema-distichiasis syndrome (LPHDST) is caused by heterozygous mutation in the FOXC2 gene (602402) on chromosome 16q24.</p><p>See also lymphatic malformation-5 (LMPHM5; 153200) and lymphedema and yellow nail syndrome (153300), which show phenotypic overlap.</p>
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<p>Lymphedema-distichiasis syndrome (LPHDST) is an autosomal dominant disorder that classically presents as lymphedema of the limbs and double rows of eyelashes (distichiasis). Irritation of the cornea, with corneal ulceration in some cases, brings the patients to the attention of ophthalmologists. Other complications may include cardiac defects, varicose veins, ptosis, cleft palate, spinal extradural cysts, and photophobia (Fang et al., 2000; Brice et al., 2002). </p>
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<strong>Clinical Features</strong>
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<p>In a family reported by Bloom (1941), lymphedema of the legs occurred in 5 generations; six affected persons in 3 consecutive generations also had ptosis.</p><p>The first description of the combination of lymphedema and distichiasis was reported by Neel and Schull (1954). Falls and Kertesz (1964) reported 4 sibs with bilateral lymphedema of the legs and distichiasis. One of the 4 had striking webbed neck, whereas 2 were thought to have mild webbing. Several of the affected persons complained of photophobia and had partial ectropion of the lateral third of the lower lids, giving them a wide-eyed appearance. The father and one of his brothers reportedly had lymphedema, distichiasis, and webbed neck, and the paternal grandmother had lymphedema. An affected paternal uncle died of metastatic fibrosarcoma originating in an edematous leg. Falls and Kertesz (1964) made brief reference to a second family in which the male proband had ptosis and lymphedema and the father ptosis. </p><p>Chynn (1967) reported lymphedema and distichiasis with spinal extradural cyst (SEDAC) in 2 black sibs, aged 12 and 10 at the time of diagnosis. Progressive weakness in the legs was the main symptom. Another sib had lymphedema and distichiasis and may have had SEDAC. Bergland (1968) reported 3 of 4 sibs affected in the pedigree reported by Chynn (1967). Spinal changes were present but asymptomatic in the affected father, daughter, and son described by Robinow et al. (1970). Hoover (1971) studied a family with the lymphedema-distichiasis syndrome in 3 generations. Cilluffo et al. (1981) noted that spinal extradural cysts are often arachnoid diverticula. </p><p>Dale (1987) noted that 'bilateral hyperplasia' lymphedema is an uncommon form of lymphedema in which lymphography shows abundant, dilated lymphatics occurring in both lower limbs, and the thoracic duct is either absent, obstructed, or deformed. Further, he noted that this form of lymphedema is often associated with other congenital malformations, including distichiasis and congenital heart disease. In a survey of 725 patients with primary lymphedema treated at St. Thomas' Hospital, Dale (1987) found 5 with distichiasis, all of whom showed bilateral hyperplasia. Of 475 patients investigated by lymphography, only 30 (6%) had bilateral hyperplasia. Of these, 11 (36%) had a positive family history, and 3 had both distichiasis and bilateral hyperplasia. Further examination of these affected families showed a variable phenotype, in that some members had both lymphedema and distichiasis, whereas others had only lymphedema. Kolin et al. (1991) described 2 cases of distichiasis, one in association with familial and congenital lymphedema with hypoplasia of lymphatics (suggesting Milroy disease), and the second in association with pubertal onset of lymphedema. </p><p>Johnson et al. (1999) described this syndrome in a 14-year-old African American girl who presented with a 3-month history of nonpitting edema beginning on the left distal leg and progressing to both lower extremities and extending to the thigh. She had had surgery for dual-chamber pacemaker placement for symptomatic bradycardia due to Mobitz type I secondary atrioventricular block and correction of supracardiac total anomalous pulmonary venous connection and patent ductus arteriosus (see 607411). The family history was notable for a maternal grandmother and a great-grandmother with lymphedema and congenital heart disease; the medical condition of the mother of the proband was unknown. Ophthalmic examination showed a bilateral double row of eyelashes without corneal abrasion. </p><p>Finegold et al. (2001) studied 11 families with lymphedema and mutations in the FOXC2 gene. Broad phenotypic heterogeneity was observed within the families, as well as overlapping phenotypically defined lymphedema syndromes: Meige lymphedema (LMPHM5; 153200), lymphedema-distichiasis syndrome, and yellow nail syndrome (153300), but not Milroy disease (LMPHM1; 153100). The authors stated that the phenotypic classification of autosomal dominant lymphedema did not appear to reflect the underlying genetic causation of these disorders. </p><p>Brice et al. (2002) described in detail the clinical findings in 74 affected subjects from 18 families, as well as 6 isolated cases, with the lymphedema-distichiasis syndrome. All patients had mutations in the FOXC2 gene, except 2 affected brothers who showed linkage to the FOXC2 gene. Fifty-seven of the 74 patients had clinical evidence of lymphedema, with the onset in males (9 to 11 years) significantly earlier than the onset in females (14 to 20 years), but penetrance appeared complete in both sexes by the age of 40 years. The lymphedema was usually bilateral and asymmetric. Lymphoscintigram in 9 patients showed abnormally low uptake of radioactive colloid in inguinal nodes, increased number of lymph conducting pathways, and lymph reflux. Distichiasis occurred in 94% of patients, 74% of whom had complications, including corneal irritation, photophobia, conjunctivitis, and styes. Ptosis was noted in 31%, congenital heart disease in 6.8%, and cleft palate in 4%. No patients had spinal extradural cysts. Five patients had renal abnormalities, including nephritis, duplex kidney, and recurrent infections. Varicose veins were present in 49% and were notable for early onset and increased prevalence compared to the general population, and Brice et al. (2002) emphasized the link between the lymphatic and vascular systems being affected. There were no apparent genotype/phenotype correlations. </p><p>Patil et al. (2004) noted that distichiasis is the most consistent feature of lymphedema-distichiasis syndrome and made observations on distichiasis without lymphedema. </p><p>Yildirim-Toruner et al. (2004) reported a German-Irish family in which 6 affected members spanning 3 generations had lymphedema-distichiasis syndrome. Four of the affected members also had renal disease, and 3 had type II diabetes mellitus (see 125853), features not usually seen in lymphedema-distichiasis syndrome. The oldest affected member of the family was 73 years old at the time of report and was on chronic renal dialysis. One of her sons, aged 45 years, had developed proteinuria at age 32 years. Renal biopsy showed chronic sclerosing glomerulopathy and chronic tubulointerstitial nephritis. One member of the family underwent renal transplantation and, shortly thereafter, pancreatic transplantation, both with excellent results. She was 36 years old at the time of report and had distichiasis but no lymphedema. </p><p>Yabuki et al. (2007) reported a Japanese family in which 10 members had variable manifestations of lymphedema-distichiasis syndrome. Spinal extradural arachnoid cysts (SEDAC) were found in 7 patients, of whom 4 had distichiasis. Two patients had isolated distichiasis, and 1 had lymphedema and distichiasis. Only 1 individual had all 3 features. Inheritance was clearly autosomal dominant. Although genetic analysis of the FOXC2 gene was not performed, the clinical features were suggestive of the diagnosis and indicated that SEDAC may be a common component. </p><p>Kumar et al. (2007) reported a 3-generation family from Jordan in which 12 members had lymphedema-distichiasis; 10 were alive at the time of the study, including a pair of affected identical twins who were discordant for the phenotype, as only 1 had lymphedema and varicose veins at age 28 years. The findings suggested that phenotypic variation in the disorder is not always due to modifying genes. All affected individuals had distichiasis, 5 had lymphedema, 4 had varicose veins, and 3 had cleft palate. </p><p>Mellor et al. (2007) examined the venous system of the leg with Duplex ultrasound in 18 FOXC2 mutation-positive individuals, including 3 without lymphedema, from 7 families with lymphedema-distichiasis syndrome previously reported by Bell et al. (2001) and Brice et al. (2002). All 18 had superficial venous reflux in the great saphenous vein, compared to only 1 of 12 controls (10 of whom were mutation-negative family members). Deep venous reflux was also recorded in 14 of the 18 mutation-positive individuals, including all 3 mutation carriers without lymphedema, compared to only 1 of 12 controls. </p><p>Rezaie et al. (2008) disputed the clinical diagnoses of some of the patients reported by Finegold et al. (2001). In particular, 10 of the 11 families reported by Finegold et al. (2001) had distichiasis, consistent with the lymphedema-distichiasis syndrome. The last family was not reported to have either yellow nails or distichiasis, but Rezaie et al. (2008) emphasized that the detection of distichiasis is often difficult to confirm and cannot be assumed to be absent from patient self-reports. In addition, Rezaie et al. (2008) did not identify mutations in the FOXC2 gene in 22 unrelated probands with Meige disease, i.e., lymphedema without distichiasis. One additional proband was found to carry a FOXC2 mutation, but detailed ophthalmologic examination revealed accessory eyelashes in him and his affected family members, thus confirming the diagnosis of lymphedema-distichiasis. The authors also noted that ptosis is a variable feature of the lymphedema-distichiasis syndrome, occurring in about 30% of patients, and suggested that lymphedema and ptosis alone do not comprise a distinct syndrome; rather, those patients likely also have distichiasis. </p><p>From a cohort of 288 patients with primary noncongenital lymphedema, van Steensel et al. (2009) reported 11 probands who were heterozygous for mutations in the FOXC2 gene. Seven of the probands had a positive family history for lymphedema, but family members were not available for study. All 11 patients had venous insufficiency, which affected the deep system in 8. Only 2 patients were reported to have distichiasis, but the authors noted that it is a feature that can be quite subtle and might have been missed. Lymphoscintigraphy performed in 1 patient with a gain-of-function missense mutation (see 602402.0016) showed minimal uptake (0.5% on the right and 1.7% on the left), indicating lack of transport consistent with lymphatic hypoplasia. </p><p>De Niear et al. (2018) reported a 3-generation family with lymphedema-distichiasis. The proband was a 4-year-old boy who presented with distichiasis and photophobia, eye rubbing, and squinting, but did not exhibit lymphedema. Examination showed that the lashes originated from the meibomian gland orifices of all 4 lids. Family history revealed that the proband's mother had distichiasis with onset of lymphedema at age 12 as well as ptosis and varicose veins. His maternal grandmother was also reported to have had lymphedema, distichiasis, and varicose veins. In addition, family pedigree showed an affected brother with distichiasis. </p>
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<p>In 3 families with lymphedema-distichiasis, Mangion et al. (1999) found linkage to 16q24.3. Subsequent analysis of the region for recombinants placed the locus between D16S422 and D16S3074, a distance of approximately 16 cM. </p><p>Erickson et al. (1995) described neonatal lymphedema, similar to that seen in Turner syndrome, associated with a Y;16 translocation in a male infant. They were not able to find a candidate gene on the Y chromosome to account for the lymphedema and turned their attention to the breakpoint in chromosome 16 at 16q24.3. When the lymphedema-distichiasis syndrome was mapped to a 16-cM region on distal chromosome 16, they determined that the breakpoint in the Y;16 translocation was within this region and narrowed the region to a 20-kb segment. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The transmission pattern of LPHDST in the families reported by Fang et al. (2000) was consistent with autosomal dominant inheritance. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 2 families with autosomal dominant lymphedema-distichiasis syndrome, Fang et al. (2000) identified heterozygous inactivating mutations in the FOXC2 gene: a nonsense mutation (602402.0001) and a frameshift mutation (602402.0002). </p><p>In affected members of the family with lymphedema-distichiasis syndrome originally reported by Falls and Kertesz (1964), Erickson et al. (2001) identified a heterozygous insertion/deletion mutation in the FOXC2 gene (602402.0011), resulting in premature termination. Erickson et al. (2001) described truncating mutations in the FOXC2 gene in 8 additional families with the disorder. </p><p>Finegold et al. (2001) identified mutations in the FOXC2 gene in 11 of 86 families with lymphedema-distichiasis syndrome (see, e.g., 602402.0007 and 602402.0008). </p><p>In 6 affected members spanning 3 generations of a German-Irish family with lymphedema-distichiasis syndrome, Yildirim-Toruner et al. (2004) identified a 1-bp insertion in the FOXC2 gene (602402.0010). Affected individuals in this family also had renal disease and diabetes mellitus. </p><p>Van Steensel et al. (2009) screened a cohort of 288 patients with primary noncongenital lymphedema for mutations in the FLT4 (136352), SOX18 (601618), and FOXC2 genes, and identified 4 mutations in FLT4 (see LMPHM1, 153100) and 11 in FOXC2. None of the FOXC2 variants were found in 100 unrelated Dutch controls or in the dbSNP (build 130) database, and all involved highly conserved residues. Five of the FOXC2 changes were predicted to truncate the protein, and 6 were missense mutations. Two of the missense mutations were located within the forkhead DNA-binding domain, including the previously reported S125L mutation (602402.0012) and an R121C substitution (602402.0014), whereas the remaining 4 occurred outside the forkhead domain (see, e.g., 602402.0015 and 602402.0016). Functional analysis in HeLa Ohio and COS-7 cells showed that all 4 FOXC2 missense mutation outside the forkhead domain increased transcriptional and transactivation activity, whereas the missense mutations within the forkhead domain showed reduced activity. No genotype/phenotype correlations were observed. The authors concluded that gain-of-function mutations in FOXC2 can also cause lymphedema. </p><p>Michelini et al. (2012) screened the FLT4 and FOXC2 genes in a cohort of 46 Italian probands with primary lymphedema and identified FLT4 mutations in 6 (13%) and FOXC2 mutations in 6 (13%; see, e.g., 602402.0017). Tavian et al. (2016) restudied the 6 Italian probands with FOXC2-associated lymphedema, 4 of whom had distichiasis upon slit-lamp examination. Consistent with previous reports, the 3 patients with activating mutations showed lymphatic hypoplasia on scintigraphy, whereas the 3 patients with inactivating mutations showed hyperplasia, suggesting a genotype/phenotype correlation. The authors stated that the association between FOXC2 function and distichiasis was less clear: all 3 patients with activating mutations had distichiasis, whereas it was present in only 1 of the 3 patients with inactivating mutations; they suggested that further studies were required to elucidate these correlations. Tavian et al. (2016) concluded that either complete loss or significant gain of FOXC2 function can cause a perturbation of lymphatic vessel formation resulting in lymphedema. </p><p>In the proband from a 3-generation family with lymphedema-distichiasis, De Niear et al. (2018) identified heterozygosity for a 2-bp insertion in the FOXC2 gene that was not found in his unaffected brother. Mutation analysis of 4 other affected family members was not done. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kriederman et al. (2003) performed dynamic lymphatic imaging and immunohistochemical examination of lymphatic tissues in mice heterozygous for a targeted disruption of Foxc2. Adult heterozygous mice characteristically exhibited a generalized lymphatic vessel and lymph node hyperplasia and rarely exhibited hindlimb swelling. Retrograde lymph flow through apparently incompetent interlymphangion valves into the mesenteric nodes, intestinal wall, and liver was also observed. In addition, Foxc2 heterozygous mice uniformly displayed distichiasis. Kriederman et al. (2003) noted that the craniofacial, cardiovascular, and skeletal abnormalities sometimes associated with lymphedema-distichiasis syndrome had previously been shown to be fully penetrant in homozygous Foxc2-null mice (Iida et al., 1997; Winnier et al., 1997). They concluded that Foxc2 haploinsufficient mice mimic closely the distinctive lymphatic and ocular phenotype of patients with lymphedema-distichiasis syndrome. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Corbett et al. (1982); Pap et al. (1980); Schwartz et al. (1980)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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<strong>Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene.</strong>
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Hum. Genet. 108: 546-551, 2001.
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Lymphology 15: 85-90, 1982.
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J. Med. Genet. 24: 170-171, 1987.
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<strong>Novel FOXC2 mutation and distichiasis in a patient with lymphedema-distichiasis syndrome.</strong>
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Erickson, R. P., Dagenais, S. L., Caulder, M. S., Downs, C. A., Herman, G., Jones, M. C., Kerstjens-Frederikse, W. S., Lidral, A. C., McDonald, M., Nelson, C. C., Witte, M., Glover, T. W.
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<strong>A 'balanced' Y;16 translocation associated with Turner-like neonatal lymphedema suggests the location of a potential anti-Turner gene on the Y chromosome.</strong>
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Falls, H. F., Kertesz, E. D.
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<strong>A new syndrome combining pterygium colli with developmental anomalies of the eyelids and lymphatics of the lower extremities.</strong>
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Fang, J., Dagenais, S. L., Erickson, R. P., Arlt, M. F., Glynn, M. W., Gorski, J. L., Seaver, L. H., Glover, T. W.
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Finegold, D. N., Kimak, M. A., Lawrence, E. C., Levinson, K. L., Cherniske, E. M., Pober, B. R., Dunlap, J. W., Ferrell, R. E.
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Iida, K., Koseki, H., Kakinuma, H., Kato, N., Mizutani-Koseki, Y., Ohucki, H., Yoshioka, H., Noji, S., Kawamura, K., Kataoka, Y., Ueno, F., Taniguchi, M., Yoshida, N., Sugiyama, T., Miura, N.
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Kolin, T., Johns, K. J., Wadlington, W. B., Butler, M. G., Sunalp, M. A., Wright, K. W.
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Kriederman, B. M., Myloyde, T. L., Witte, M. H., Dagenais, S. L., Witte, C. L., Rennels, M., Bernas, M. J., Lynch, M. T., Erickson, R. P., Caulder, M. S., Miura, N., Jackson, D., Brooks, B. P., Glover, T. W.
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<strong>FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.</strong>
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Kumar, S., Carver, C., McCall, S., Brice, G., Ostergaard, P., Mortimer, P., Jeffery, S., Lymphoedema Consortium.
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<strong>A family with lymphoedema-distichiasis where identical twins have a discordant phenotype. (Letter)</strong>
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Mangion, J., Rahman, N., Mansour, S., Brice, G., Rosbotham, J., Child, A. H., Murday, V. A., Mortimer, P. S., Barfoot, R., Sigurdsson, A., Edkins, S., Sarfarazi, M., Burnand, K., Evans, A. L., Nunan, T. O., Stratton, M. R., Jeffery, S.
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<strong>A gene for lymphedema-distichiasis maps to 16q24.3.</strong>
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Am. J. Hum. Genet. 65: 427-432, 1999.
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[PubMed: 10417285]
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[Full Text: https://doi.org/10.1086/302500]
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<p class="mim-text-font">
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Mellor, R. H., Brice, G., Stanton, A. W. B., French, J., Smith, A., Jeffery, S., Levick, J. R., Burnand, K. G., Mortimer, P. S.
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<strong>Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb.</strong>
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Circulation 115: 1912-1920, 2007.
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<p class="mim-text-font">
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Michelini, S., Degiorgio, D., Cestari, M., Corda, D., Ricci, M., Cardone, M., Mander, A., Famoso, L., Contini, E., Serrani, R., Pinelli, L., Cecchin, S., Bertelli, M.
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<strong>Clinical and genetic study of 46 Italian patients with primary lymphedema.</strong>
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Lymphology 45: 3-12, 2012. Note: Erratum: Lymphology 45: 87-88, 2012.
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[PubMed: 22768468]
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<p class="mim-text-font">
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Neel, J. V., Schull, W. J.
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<strong>Human Heredity.</strong>
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Chicago: Univ. of Chicago Press (pub.) 1954. Pp. 50-51.
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<p class="mim-text-font">
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Pap, Z., Biro, T., Szabo, L., Papp, Z.
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<strong>Syndrome of lymphoedema and distichiasis.</strong>
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|
Hum. Genet. 53: 309-310, 1980.
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[PubMed: 7372334]
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[Full Text: https://doi.org/10.1007/BF00287047]
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</p>
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<p class="mim-text-font">
|
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Patil, B. B., Bell, R., Brice, G., Jeffery, S., Dessai, S. P.
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<strong>Distichiasis without lymphedema?</strong>
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|
Eye 18: 1270-1272, 2004.
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[PubMed: 15044942]
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[Full Text: https://doi.org/10.1038/sj.eye.6701387]
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Rezaie, T., Ghoroghchian, R., Bell, R., Brice, G., Hasan, A., Burnand, K., Vernon, S., Mansour, S., Mortimer, P., Jeffery, S., Child, A., Sarfarazi, M.
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<strong>Primary non-syndromic lymphoedema (Meige disease) is not caused by mutations in FOXC2.</strong>
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Robinow, M., Johnson, G. F., Verhagen, A. D.
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<strong>Distichiasis-lymphedema: a hereditary syndrome of multiple congenital defects.</strong>
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Am. J. Dis. Child. 119: 343-347, 1970.
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[PubMed: 5434594]
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Schwartz, J. F., O'Brien, M. S., Hoffman, J. C., Jr.
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<strong>Hereditary spinal arachnoid cysts, distichiasis, and lymphedema.</strong>
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Ann. Neurol. 7: 340-343, 1980.
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[PubMed: 7377759]
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[Full Text: https://doi.org/10.1002/ana.410070410]
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Tavian, D., Missaglia, S., Maltese, P. E., Michelini, S., Fiorentino, A., Ricci, M., Serrani, R., Walter, M. A., Bertelli, M.
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<strong>FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function.</strong>
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Oncotarget 7: 54228-54239, 2016.
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van Steensel, M. A. M., Damstra, R. J., Heitink, M. V., Bladergroen, R. S., Veraart, J., Steijlen, P. M., van Geel, M.
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<strong>Novel missense mutations in the FOXC2 gene alter transcriptional activity.</strong>
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Hum. Mutat. 30: E1002-E1009, 2009. Note: Electronic Article.
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[PubMed: 19760751]
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Winnier, G. E., Hargett, L., Hogan, B. L. M.
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<strong>The winged helix transcription factor MFH1 is required for proliferation and patterning of paraxial mesoderm in the mouse embryo.</strong>
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Yabuki, S., Kikuchi, S., Ikegawa, S.
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<strong>Spinal extradural arachnoid cysts associated with distichiasis and lymphedema.</strong>
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[PubMed: 17366583]
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Yildirim-Toruner, C., Subramanian, K., El Manjra, L., Chen, E., Goldstein, S., Vitale, E.
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<strong>A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema-distichiasis syndrome associated with renal disease and diabetes mellitus.</strong>
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[PubMed: 15523639]
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Marla J. F. O'Neill - updated : 01/02/2019<br>Marla J. F. O'Neill - updated : 7/10/2008<br>Cassandra L. Kniffin - updated : 8/29/2007<br>Cassandra L. Kniffin - updated : 5/17/2007<br>George E. Tiller - updated : 2/25/2005<br>Victor A. McKusick - updated : 1/21/2005<br>Cassandra L. Kniffin - reorganized : 11/19/2003<br>Cassandra L. Kniffin - updated : 11/12/2003<br>Michael J. Wright - updated : 10/22/2002<br>Victor A. McKusick - updated : 12/12/2000<br>Victor A. McKusick - updated : 1/11/2000<br>Victor A. McKusick - updated : 6/3/1999
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Victor A. McKusick : 6/2/1986
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