3189 lines
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Entry
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- #255700 - MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE
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- OMIM
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<p>
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<span class="h4">#255700</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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<li role="presentation">
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<a href="/clinicalSynopsis/255700"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</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="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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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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</ul>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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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>
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<div id="mimExternalLinksFold" class="collapse in">
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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=MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE" 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=75&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/NBK1355/" 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/myotonia-congenita" 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=255700[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=614" 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 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:0081335" 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/255700" 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://omia.org/OMIA000698/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0081335" 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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<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="mimCellLines">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:255700" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</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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</span>
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</span>
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</div>
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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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<div>
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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> 20305008<br />
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<strong>ICD10CM:</strong> G71.12<br />
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<strong>ORPHA:</strong> 614<br />
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<strong>DO:</strong> 0081335<br />
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">ICD+</a>
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</div>
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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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255700
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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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MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE
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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">
|
|
BECKER DISEASE<br />
|
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MYOTONIA, GENERALIZED
|
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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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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</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>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/770?start=-3&limit=10&highlight=770">
|
|
7q34
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myotonia congenita, recessive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/255700"> 255700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CLCN1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/118425"> 118425 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/255700" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/255700" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/255700" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> 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">
|
|
|
|
- Eyelid myotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749493&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749493</a>]</span><br /> -
|
|
Lid lag <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/89893000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">89893000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234664&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234664</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025605" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025605</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025605" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025605</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Tongue myotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749494</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Myotonia (usually occurs during rapid voluntary muscle movements after a period of rest) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850659</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3434004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3434004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span><br /> -
|
|
Muscle stiffness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221170</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003552</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003552</a>]</span><br /> -
|
|
Muscle pain <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68962001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68962001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M79.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M79.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231528</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003326</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003326" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003326</a>]</span><br /> -
|
|
Delayed relaxation of muscle fibers after contraction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3434004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3434004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700153&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700153</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002486</a>]</span><br /> -
|
|
Percussion myotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751359&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751359</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010548</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010548</a>]</span><br /> -
|
|
Handgrip myotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1868623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1868623</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012899" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012899</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012899" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012899</a>]</span><br /> -
|
|
Muscle hypertrophy of the lower extremities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850663&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850663</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008968</a>]</span><br /> -
|
|
Transient muscle weakness occur in 75% of patients, particularly in the arms and hands <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850664&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850664</a>]</span><br /> -
|
|
Spontaneous, repetitive electrical activity ('myotonic runs') seen on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5542319&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5542319</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
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|
|
|
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|
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|
|
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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 in childhood<br /> -
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Highly variable phenotype and severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850667&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850667</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
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See also autosomal dominant form (<a href="/entry/160800">160800</a>), which is less common and less severe<br />
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- Caused by mutation in the skeletal muscle chloride channel-1 gene (CLCN1, <a href="/entry/118425#0001">118425.0001</a>)<br />
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<p>A number sign (#) is used with this entry because of evidence that autosomal recessive myotonia congenita (Becker disease) is caused by homozygous or compound heterozygous mutation in the gene encoding skeletal muscle chloride channel-1 (CLCN1; <a href="/entry/118425">118425</a>) on chromosome 7q34.</p><p>Autosomal dominant myotonia congenita, or Thomsen disease (<a href="/entry/160800">160800</a>), is caused by heterozygous mutation in the CLCN1 gene.</p>
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<p>Autosomal recessive myotonia congenita is a nondystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. Some patients show transient muscle weakness (<a href="#8" class="mim-tip-reference" title="Koch, M. C., Ricker, K., Otto, M., Wolf, F., Zoll, B., Lorenz, C., Steinmeyer, K., Jentsch, T. J. <strong>Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker).</strong> J. Med. Genet. 30: 914-917, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8301644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8301644</a>] [<a href="https://doi.org/10.1136/jmg.30.11.914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8301644">Koch et al., 1993</a>). Becker disease is more common and more severe than Thomsen disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8301644" 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="Te Kamp, (NI). <strong>Ein Beitrag zur Kenntnis der Myotonia congenita sog. Thomsenschen Krankheit.</strong> Dtsch. Med. Wschr. 33: 1005 only, 1907."None>Te Kamp (1907)</a> reported possible homozygosity in cases of myotonia congenita.</p><p><a href="#1" class="mim-tip-reference" title="Becker, P. E. <strong>Zur Genetik der Myotonien. In: Kuhn, E.: Progressive Muskeldystrophie, Myotonie, Myasthenie.</strong> Berlin: Springer-Verlag (pub.) 1966. Pp. 247-255."None>Becker (1966)</a> concluded that a recessive form of myotonia congenita is more frequent and more severe than the dominant myotonia congenita of Thomsen. Segregation ratios and the frequency of parental consanguinity suggested recessive inheritance. <a href="#21" class="mim-tip-reference" title="Winters, J. L., McLaughlin, L. A. <strong>Myotonia congenita: a review of four cases.</strong> J. Bone Joint Surg. Am. 52: 1345-1350, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5469190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5469190</a>]" pmid="5469190">Winters and McLaughlin (1970)</a> described myotonia congenita in 2 brothers and a sister with normal parents. <a href="#6" class="mim-tip-reference" title="Harper, P. S., Johnston, D. M. <strong>Recessively inherited myotonia congenita.</strong> J. Med. Genet. 9: 213-215, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5046632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5046632</a>] [<a href="https://doi.org/10.1136/jmg.9.2.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5046632">Harper and Johnston (1972)</a> reported a particularly interesting family in which 3 children of first-cousin parents were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5469190+5046632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Becker, P. E. <strong>Myotonia congenita and syndromes associated with myotonia. Vol. III. Topics in Human Genetics.</strong> Stuttgart: Georg Thieme (pub.) 1977."None>Becker (1977)</a> reviewed the features distinguishing recessive from dominant myotonia. Although called myotonia congenita, the recessive form is not manifest at birth; it manifests between 4 and 12 years and, especially in males, as late as 18 years. It is a progressive disorder, starting in the legs and in a few years affecting the arms and finally the masticatory and facial muscles.</p><p><a href="#7" class="mim-tip-reference" title="Heiman-Patterson, T., Martino, C., Rosenberg, H., Fletcher, J., Tahmoush, A. <strong>Malignant hyperthermia in myotonia congenita.</strong> Neurology 38: 810-812, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3362383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3362383</a>] [<a href="https://doi.org/10.1212/wnl.38.5.810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3362383">Heiman-Patterson et al. (1988)</a> described 2 sisters with myotonia congenita who, on halothane contracture testing of skeletal muscle in vitro, had findings consistent with susceptibility to malignant hyperthermia (<a href="/entry/145600">145600</a>). The proposita was a 31-year-old woman who developed generalized muscle stiffness on exposure to succinylcholine. Intubation was difficult and she had generalized muscle stiffness, including opisthotonos and decerebrate posturing. Lifelong clumsiness and rare cramping were the only neuromuscular complaints, and there was no clinical myotonia. A 42-year-old sister had a positive contracture test and, by history, muscle stiffness since early childhood that increased with exercise and involved her hands and eyelids. During 2 surgical procedures, she developed muscle rigidity without rise in temperature on exposure to succinylcholine. Neurologic examination showed lid lag and myotonia in all muscles tested. In both patients, slit-lamp was negative for the changes of myotonic dystrophy, and the EKG was normal. No information was provided on the parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3362383" 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="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> reported 27 French Canadian patients with autosomal recessive myotonia associated with biallelic CLCN1 mutations (see, e.g., <a href="/entry/118425#0009">118425.0009</a>; <a href="/entry/118425#0015">118425.0015</a>; <a href="/entry/118425#0019">118425.0019</a>). The mean age at onset was 10 years (range, 3 to 34). Clinical features included lid lag (26%), lid myotonia (37%), tongue myotonia (63%), percussion myotonia (96%), handgrip myotonia (89%), transient weakness (48%), warm-up phenomenon (100%), generalized hypertrophy (55%), generalized stiffness (93%), muscle pain (41%), exacerbation with cold temperatures (63%) and a hormonal effect in women (46%). This latter subset of woman reported aggravation of symptoms during menstrual periods, aggravation during pregnancy, or alleviation after menopause. In addition, some patients reported that alcohol alleviated symptoms. Many patients took medication for symptom alleviation. Although some were resistant, the most effective medications were phenytoin and gabapentin. Electrophysiologic studies showed more severe myotonia and larger CMAP decrements on repetitive nerve stimulation compared to patients with dominant myotonia due to heterozygous CLCN1 mutations. <a href="#4" class="mim-tip-reference" title="Dupre, N., Chrestian, N., Bouchard, J.-P., Rossignol, E., Brunet, D., Sternberg, D., Brias, B., Mathieu, J., Puymirat, J. <strong>Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.</strong> Neuromusc. Disord. 19: 330-334, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337100</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337100">Dupre et al. (2009)</a> noted that the short exercise test is less painful, but just as accurate as repetitive nerve stimulation in assessing CMAP decrements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337100" 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>Among 22 patients with paramyotonia congenita (PMC; <a href="/entry/168300">168300</a>), 14 with sodium channel myotonia (<a href="/entry/608390">608390</a>), and 18 myotonia patients with mutations in the CLCN1 gene, <a href="#5" class="mim-tip-reference" title="Fournier, E., Viala, K., Gervais, H., Sternberg, D., Arzel-Hezode, M., Laforet, P., Eymard, B., Tabti, N., Willer, J.-C., Vial, C., Fontaine, B. <strong>Cold extends electromyography distinction between ion channel mutations causing myotonia.</strong> Ann. Neurol. 60: 356-365, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16786525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16786525</a>] [<a href="https://doi.org/10.1002/ana.20905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16786525">Fournier et al. (2006)</a> found that cold temperature was able to exaggerate electromyographic findings in a way that enabled a clear correlation between EMG findings and genetic defects. Those with PMC showed a clear worsening of compound muscle action potential with cold temperature. Those with sodium channel myotonia tended not to show a decline in compound action muscle potentials, whereas those with myotonia due to CLCN1 mutations tended to show improvement of the muscle potential with exercise, concomitant with the clinical warm-up phenomenon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16786525" 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>Using both a TCRB (<a href="/entry/186940">186940</a>) probe and a CLCN1 probe, <a href="#9" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> demonstrated linkage of the recessive form of generalized myotonia to the CLCN1 gene on chromosome 7q35 (maximum lod = 4.69 at theta = 0.0). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379744" 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 myotonia congenita in the family reported by <a href="#9" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379744" 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 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita, <a href="#9" class="mim-tip-reference" title="Koch, M. C., Steinmeyer, K., Lorenz, C., Ricker, K., Wolf, F., Otto, M., Zoll, B., Lehmann-Horn, F., Grzeschik, K.-H., Jentsch, T. J. <strong>The skeletal muscle chloride channel in dominant and recessive human myotonia.</strong> Science 257: 797-800, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1379744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1379744</a>] [<a href="https://doi.org/10.1126/science.1379744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1379744">Koch et al. (1992)</a> identified a homozygous mutation in the CLCN1 gene (<a href="/entry/118425#0001">118425.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1379744" 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 a German family with recessive myotonia, <a href="#11" class="mim-tip-reference" title="Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M. C., Jentsch, T. J. <strong>Genomic organization of the human muscle chloride channel CLC-1 and analysis of novel mutations leading to Becker-type myotonia.</strong> Hum. Molec. Genet. 3: 941-946, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951242</a>] [<a href="https://doi.org/10.1093/hmg/3.6.941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951242">Lorenz et al. (1994)</a> identified compound heterozygosity for 2 mutations in the CLCN1 gene (<a href="/entry/118425#0003">118425.0003</a>; <a href="/entry/118425#0004">118425.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951242" 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 18 unrelated families from Norway and Sweden with both autosomal dominant (5 families) and autosomal recessive (13 families) inheritance of myotonia congenita, <a href="#17" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> identified 8 different mutations in the CLCN1 gene. Fifteen patients had mutations on both alleles, consistent with the recessive disorder; 2 probands had mutations in a single allele; and 2 probands had no CLCN1 mutations. In 2 families, 3 CLCN1 mutations were found in the proband, and <a href="#17" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> suspected that this phenomenon may be underestimated because mutation search in a disease gene usually ends by the identification of 2 mutations in a family with recessive inheritance. Families with apparently dominant segregation of myotonia congenita may actually represent recessive inheritance with undetected heterozygous individuals married-in as a consequence of a high population carrier frequency of some mutations. The findings, together with the very variable clinical presentation, challenged the classification into dominant Thomsen or recessive Becker disease. <a href="#17" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> suggested that most cases of myotonia congenita show recessive inheritance with some modifying factors or genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> performed multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene in 60 families with recessive myotonia congenita in whom either no mutations or only a single pathogenic CLCN1 mutation had been identified. The results were positive in 4 (6.7%) patients: 2 unrelated patients were found to have 2 different multiexon deletions within the CLCN1 gene on the second allele, and 2 additional patients had a homozygous duplication of exons 8 through 14 of the CLCN1 gene (<a href="/entry/118425#0020">118425.0020</a>). The 2 patients with the duplication were both of Iraqi origin, but were unrelated. Both Iraqi patients had a severe form of the disorder with onset in infancy. Haplotype analysis suggested a founder effect for this duplication mutation. <a href="#12" class="mim-tip-reference" title="Raja Rayan, D. L., Haworth, A., Sud, R., Matthews, E., Fialho, D., Burge, J., Portaro, S., Schorge, S., Tuin, K., Lunt, P., McEntagart, M., Toscano, A., Davis, M. B., Hanna, M. G. <strong>A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.</strong> Neurology 78: 1953-1958, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22649220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22649220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22649220[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/10.1212/WNL.0b013e318259e19c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22649220">Raja Rayan et al. (2012)</a> concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22649220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Suetterlin, K., Matthews, E., Sud, R., McCall, S., Fialho, D., Burge, J., Jayaseelan, D., Haworth, A., Sweeney, M. G., Kullmann, D. M., Schorge, S., Hanna, M. G., Mannikko, R. <strong>Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.</strong> Brain 145: 607-620, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34529042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34529042</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34529042[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/10.1093/brain/awab344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34529042">Suetterlin et al. (2022)</a> evaluated the functional significance of 95 CLCN1 mutations, including 34 novel mutations, identified in 233 patients with myotonia congenita. Mutations that altered voltage dependence of activation clustered in the first half of the transmembrane domains and mutations resulting in absent currents clustered in the second half of the transmembrane domains. Mutations that resulted in dominant functional features clustered in the TM1 domain and variants associated with recessive functional features and without a shift in voltage dependence of activation were clustered in the TM2 domain. Mutations in the intracellular domain were not associated with a dominant inheritance pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34529042" 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="#17" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> stated that the worldwide prevalence of myotonic congenita, both dominant and recessive forms, is 1:100,000. In the northern Norwegian population, <a href="#17" class="mim-tip-reference" title="Sun, C., Tranebjaerg, L., Torbergsen, T., Holmgren, G., Van Ghelue, M. <strong>Spectrum of CLCN1 mutations in patients with myotonia congenita in northern Scandinavia.</strong> Europ. J. Hum. Genet. 9: 903-909, 2001. Note: Erratum: Europ. J. Hum. Genet. 18: 264 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11840191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11840191</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200736" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11840191">Sun et al. (2001)</a> found a prevalence of about 9:100,000, which was comparable to the Finnish experience. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11840191" 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 Adr/Adr ('arrested development of righting') homozygous mouse is an animal model for autosomal recessive myotonia (<a href="#20" class="mim-tip-reference" title="Watkins, W. J., Watts, D. C. <strong>Biological features of the new A2G-adr mouse mutant with abnormal muscle function.</strong> Lab. Anim. 18: 1-6, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10628777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10628777</a>] [<a href="https://doi.org/10.1258/002367784780865036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10628777">Watkins and Watts, 1984</a>; <a href="#13" class="mim-tip-reference" title="Rudel, R. <strong>The myotonic mouse--a realistic model for the study of human recessive generalized myotonia.</strong> Trends Neurosci. 13: 1-3, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1688667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1688667</a>] [<a href="https://doi.org/10.1016/0166-2236(90)90049-g" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1688667">Rudel, 1990</a>; <a href="#10" class="mim-tip-reference" title="Koltgen, D., Brinkmeier, H., Jockusch, H. <strong>Myotonia and neuromuscular transmission in the mouse.</strong> Muscle Nerve 14: 775-780, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1653899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1653899</a>] [<a href="https://doi.org/10.1002/mus.880140813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1653899">Koltgen et al., 1991</a>). <a href="#14" class="mim-tip-reference" title="Steinmeyer, K., Klocke, R., Ortland, C., Gronemeier, M., Jockusch, H., Grunder, S., Jentsch, T. J. <strong>Inactivation of muscle chloride channel by transposon insertion in myotonic mice.</strong> Nature 354: 304-308, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659665</a>] [<a href="https://doi.org/10.1038/354304a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659665">Steinmeyer et al. (1991)</a> observed changes in chloride ion conductance in skeletal muscle of homozygous Adr/Adr mice and found that experimental blockage of chloride ion conductance in muscle elicited myotonia. <a href="#15" class="mim-tip-reference" title="Steinmeyer, K., Ortland, C., Jentsch, T. J. <strong>Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel.</strong> Nature 354: 301-304, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1659664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1659664</a>] [<a href="https://doi.org/10.1038/354301a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1659664">Steinmeyer et al. (1991)</a> demonstrated that the Adr mouse phenotype is caused by an inactivating mutation in the Clcn1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1659665+1653899+1688667+10628777+1659664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Zur Genetik der Myotonien. In: Kuhn, E.: Progressive Muskeldystrophie, Myotonie, Myasthenie.</strong>
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Berlin: Springer-Verlag (pub.) 1966. Pp. 247-255.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/437775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">437775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=437775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5469190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5469190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5469190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 05/27/2022
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Cassandra L. Kniffin - updated : 3/11/2013<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 12/3/2008<br>Cassandra L. Kniffin - reorganized : 6/29/2005<br>Michael B. Petersen - updated : 8/19/2002
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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carol : 10/13/2023
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carol : 05/27/2022<br>carol : 05/23/2016<br>alopez : 3/12/2013<br>ckniffin : 3/11/2013<br>ckniffin : 10/31/2011<br>terry : 1/14/2011<br>terry : 4/30/2010<br>wwang : 11/16/2009<br>ckniffin : 10/27/2009<br>wwang : 12/4/2008<br>ckniffin : 12/3/2008<br>carol : 6/29/2005<br>carol : 6/29/2005<br>ckniffin : 6/20/2005<br>cwells : 11/10/2003<br>alopez : 8/19/2002<br>terry : 2/12/2001<br>carol : 11/9/1999<br>carol : 5/12/1998<br>mimman : 2/8/1996<br>mimadm : 4/8/1994<br>warfield : 3/9/1994<br>carol : 12/20/1993<br>carol : 12/14/1992<br>carol : 9/29/1992<br>carol : 4/7/1992
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<span class="mim-font">
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<strong>#</strong> 255700
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MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE
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<span class="mim-font">
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BECKER DISEASE<br />
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MYOTONIA, GENERALIZED
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<strong>SNOMEDCT:</strong> 20305008;
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<strong>ICD10CM:</strong> G71.12;
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<strong>ORPHA:</strong> 614;
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<strong>DO:</strong> 0081335;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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7q34
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Myotonia congenita, recessive
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<span class="mim-font">
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255700
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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CLCN1
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118425
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<p>A number sign (#) is used with this entry because of evidence that autosomal recessive myotonia congenita (Becker disease) is caused by homozygous or compound heterozygous mutation in the gene encoding skeletal muscle chloride channel-1 (CLCN1; 118425) on chromosome 7q34.</p><p>Autosomal dominant myotonia congenita, or Thomsen disease (160800), is caused by heterozygous mutation in the CLCN1 gene.</p>
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<strong>Description</strong>
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<p>Autosomal recessive myotonia congenita is a nondystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. Some patients show transient muscle weakness (Koch et al., 1993). Becker disease is more common and more severe than Thomsen disease. </p>
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<strong>Clinical Features</strong>
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<p>Te Kamp (1907) reported possible homozygosity in cases of myotonia congenita.</p><p>Becker (1966) concluded that a recessive form of myotonia congenita is more frequent and more severe than the dominant myotonia congenita of Thomsen. Segregation ratios and the frequency of parental consanguinity suggested recessive inheritance. Winters and McLaughlin (1970) described myotonia congenita in 2 brothers and a sister with normal parents. Harper and Johnston (1972) reported a particularly interesting family in which 3 children of first-cousin parents were affected. </p><p>Becker (1977) reviewed the features distinguishing recessive from dominant myotonia. Although called myotonia congenita, the recessive form is not manifest at birth; it manifests between 4 and 12 years and, especially in males, as late as 18 years. It is a progressive disorder, starting in the legs and in a few years affecting the arms and finally the masticatory and facial muscles.</p><p>Heiman-Patterson et al. (1988) described 2 sisters with myotonia congenita who, on halothane contracture testing of skeletal muscle in vitro, had findings consistent with susceptibility to malignant hyperthermia (145600). The proposita was a 31-year-old woman who developed generalized muscle stiffness on exposure to succinylcholine. Intubation was difficult and she had generalized muscle stiffness, including opisthotonos and decerebrate posturing. Lifelong clumsiness and rare cramping were the only neuromuscular complaints, and there was no clinical myotonia. A 42-year-old sister had a positive contracture test and, by history, muscle stiffness since early childhood that increased with exercise and involved her hands and eyelids. During 2 surgical procedures, she developed muscle rigidity without rise in temperature on exposure to succinylcholine. Neurologic examination showed lid lag and myotonia in all muscles tested. In both patients, slit-lamp was negative for the changes of myotonic dystrophy, and the EKG was normal. No information was provided on the parents. </p><p>Dupre et al. (2009) reported 27 French Canadian patients with autosomal recessive myotonia associated with biallelic CLCN1 mutations (see, e.g., 118425.0009; 118425.0015; 118425.0019). The mean age at onset was 10 years (range, 3 to 34). Clinical features included lid lag (26%), lid myotonia (37%), tongue myotonia (63%), percussion myotonia (96%), handgrip myotonia (89%), transient weakness (48%), warm-up phenomenon (100%), generalized hypertrophy (55%), generalized stiffness (93%), muscle pain (41%), exacerbation with cold temperatures (63%) and a hormonal effect in women (46%). This latter subset of woman reported aggravation of symptoms during menstrual periods, aggravation during pregnancy, or alleviation after menopause. In addition, some patients reported that alcohol alleviated symptoms. Many patients took medication for symptom alleviation. Although some were resistant, the most effective medications were phenytoin and gabapentin. Electrophysiologic studies showed more severe myotonia and larger CMAP decrements on repetitive nerve stimulation compared to patients with dominant myotonia due to heterozygous CLCN1 mutations. Dupre et al. (2009) noted that the short exercise test is less painful, but just as accurate as repetitive nerve stimulation in assessing CMAP decrements. </p>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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<span class="mim-text-font">
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<p>Among 22 patients with paramyotonia congenita (PMC; 168300), 14 with sodium channel myotonia (608390), and 18 myotonia patients with mutations in the CLCN1 gene, Fournier et al. (2006) found that cold temperature was able to exaggerate electromyographic findings in a way that enabled a clear correlation between EMG findings and genetic defects. Those with PMC showed a clear worsening of compound muscle action potential with cold temperature. Those with sodium channel myotonia tended not to show a decline in compound action muscle potentials, whereas those with myotonia due to CLCN1 mutations tended to show improvement of the muscle potential with exercise, concomitant with the clinical warm-up phenomenon. </p>
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<h4>
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>Using both a TCRB (186940) probe and a CLCN1 probe, Koch et al. (1992) demonstrated linkage of the recessive form of generalized myotonia to the CLCN1 gene on chromosome 7q35 (maximum lod = 4.69 at theta = 0.0). </p>
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<strong>Inheritance</strong>
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<span class="mim-text-font">
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<p>The transmission pattern of myotonia congenita in the family reported by Koch et al. (1992) was consistent with autosomal recessive inheritance. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>In 3 brothers, born of consanguineous parents, with autosomal recessive myotonia congenita, Koch et al. (1992) identified a homozygous mutation in the CLCN1 gene (118425.0001). </p><p>In affected members of a German family with recessive myotonia, Lorenz et al. (1994) identified compound heterozygosity for 2 mutations in the CLCN1 gene (118425.0003; 118425.0004). </p><p>In affected members of 18 unrelated families from Norway and Sweden with both autosomal dominant (5 families) and autosomal recessive (13 families) inheritance of myotonia congenita, Sun et al. (2001) identified 8 different mutations in the CLCN1 gene. Fifteen patients had mutations on both alleles, consistent with the recessive disorder; 2 probands had mutations in a single allele; and 2 probands had no CLCN1 mutations. In 2 families, 3 CLCN1 mutations were found in the proband, and Sun et al. (2001) suspected that this phenomenon may be underestimated because mutation search in a disease gene usually ends by the identification of 2 mutations in a family with recessive inheritance. Families with apparently dominant segregation of myotonia congenita may actually represent recessive inheritance with undetected heterozygous individuals married-in as a consequence of a high population carrier frequency of some mutations. The findings, together with the very variable clinical presentation, challenged the classification into dominant Thomsen or recessive Becker disease. Sun et al. (2001) suggested that most cases of myotonia congenita show recessive inheritance with some modifying factors or genetic heterogeneity. </p><p>Raja Rayan et al. (2012) performed multiplex ligation-dependent probe amplification (MLPA) specific to the CLCN1 gene in 60 families with recessive myotonia congenita in whom either no mutations or only a single pathogenic CLCN1 mutation had been identified. The results were positive in 4 (6.7%) patients: 2 unrelated patients were found to have 2 different multiexon deletions within the CLCN1 gene on the second allele, and 2 additional patients had a homozygous duplication of exons 8 through 14 of the CLCN1 gene (118425.0020). The 2 patients with the duplication were both of Iraqi origin, but were unrelated. Both Iraqi patients had a severe form of the disorder with onset in infancy. Haplotype analysis suggested a founder effect for this duplication mutation. Raja Rayan et al. (2012) concluded that copy number variation involving the CLCN1 gene is an important genetic mechanism in patients with recessive myotonia congenita, and that MLPA analysis may aid in genetic counseling. </p><p>Suetterlin et al. (2022) evaluated the functional significance of 95 CLCN1 mutations, including 34 novel mutations, identified in 233 patients with myotonia congenita. Mutations that altered voltage dependence of activation clustered in the first half of the transmembrane domains and mutations resulting in absent currents clustered in the second half of the transmembrane domains. Mutations that resulted in dominant functional features clustered in the TM1 domain and variants associated with recessive functional features and without a shift in voltage dependence of activation were clustered in the TM2 domain. Mutations in the intracellular domain were not associated with a dominant inheritance pattern. </p>
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<p>Sun et al. (2001) stated that the worldwide prevalence of myotonic congenita, both dominant and recessive forms, is 1:100,000. In the northern Norwegian population, Sun et al. (2001) found a prevalence of about 9:100,000, which was comparable to the Finnish experience. </p>
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<strong>Animal Model</strong>
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<p>The Adr/Adr ('arrested development of righting') homozygous mouse is an animal model for autosomal recessive myotonia (Watkins and Watts, 1984; Rudel, 1990; Koltgen et al., 1991). Steinmeyer et al. (1991) observed changes in chloride ion conductance in skeletal muscle of homozygous Adr/Adr mice and found that experimental blockage of chloride ion conductance in muscle elicited myotonia. Steinmeyer et al. (1991) demonstrated that the Adr mouse phenotype is caused by an inactivating mutation in the Clcn1 gene. </p>
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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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Becker (1979); Sun and Streib (1983)
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<strong>REFERENCES</strong>
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</span>
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</h4>
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