2652 lines
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2652 lines
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Entry
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- #616878 - METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION; MECRCN
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<p>
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<span class="h4">#616878</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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<li role="presentation">
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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/616878"><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="#molecularGenetics">Molecular Genetics</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 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 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=METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION" 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=25224&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/NBK476443/" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=616878[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=480864" 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 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 class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0081386" 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/616878" 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:0081386" 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>
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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> 1172698005<br />
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<strong>ORPHA:</strong> 480864<br />
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<strong>DO:</strong> 0081386<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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616878
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</span>
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</span>
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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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METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION; MECRCN
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</span>
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</h3>
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<div>
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<br />
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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>
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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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</th>
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</thead>
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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/22/54?start=-3&limit=10&highlight=54">
|
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22q11.21
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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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Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
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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/616878"> 616878 </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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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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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</td>
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<td>
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<span class="mim-font">
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TANGO2
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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/616830"> 616830 </a>
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</span>
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</td>
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</tr>
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</tbody>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/616878" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/616878" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/616878" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 />
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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>
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<div>
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<span class="h5 mim-font">
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Head </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Microcephaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" 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 />
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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>
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<span class="h5 mim-font">
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<em> Face </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Myopathic facies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26432009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26432009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0332615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332615</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</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>
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<span class="h5 mim-font">
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<em> Ears </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Hearing loss, sensorineural (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</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>
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<span class="h5 mim-font">
|
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<em> Eyes </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Optic atrophy (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</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>
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<span class="h5 mim-font">
|
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<em> Mouth </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Drooling <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62718007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62718007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0003781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003781</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>]</span><br /> -
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|
Oropharyngeal dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71457002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71457002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.12" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.12</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0267071&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0267071</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200136" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200136</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200136" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200136</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>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> CARDIOVASCULAR </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Heart </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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|
- Long QTc interval, intermittent <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227514</a>]</span><br /> -
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|
Premature ventricular contraction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/251175005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">251175005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006682" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006682</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006682" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006682</a>]</span><br /> -
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Ventricular tachycardia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/164895002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">164895002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25569003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25569003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I47.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I47.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0344428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344428</a>, <a href="https://bioportal.bioontology.org/search?q=C0042514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042514</a>, <a href="https://bioportal.bioontology.org/search?q=C2108113&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2108113</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004756</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004756</a>]</span><br /> -
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|
Torsade de pointes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31722008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31722008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I47.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I47.21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001664</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001664" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001664</a>]</span><br /> -
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Ventricular fibrillation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/164896001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">164896001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71908006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71908006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.01</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042510</a>, <a href="https://bioportal.bioontology.org/search?q=C0344435&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344435</a>, <a href="https://bioportal.bioontology.org/search?q=C2108112&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2108112</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001663</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001663</a>]</span><br /> -
|
|
Cardiac arrest <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397829000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397829000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/410429000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">410429000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I46</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001695</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001695</a>]</span><br /> -
|
|
Brugada pattern on electrocardiogram (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227513&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227513</a>]</span><br /> -
|
|
Cardiomyopathy, hypertrophic (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</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>
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<div>
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CHEST </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Breasts </em>
|
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</span>
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</div>
|
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<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Premature thelarche (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/102889008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">102889008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E30.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E30.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0425772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0425772</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010314" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010314</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010314" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010314</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>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Skull </em>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
|
- Microcephaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" 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 />
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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>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br /> -
|
|
Rhabdomyolysis, episodic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675271&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675271</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/240131006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">240131006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/89010004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">89010004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.82</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/728.88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">728.88</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003201" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003201</a>]</span><br /> -
|
|
Normal respiratory chain studies seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227523&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227523</a>]</span><br /> -
|
|
Normal histopathology seen on muscle biopsy (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227522&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227522</a>]</span><br /> -
|
|
Nonspecific myopathic changes seen on biopsy (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549998</a>]</span><br /> -
|
|
Neurogenic atrophy of muscle fibers seen on biopsy (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227520</a>]</span><br /> -
|
|
Hemihypertrophy of right arm and leg (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227519&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227519</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> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Neurodegeneration, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span><br /> -
|
|
Global developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
|
|
Absent speech/nonverbal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227529&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227529</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
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Dysarthric speech <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
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Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Weakness in lower extremities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836296&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836296</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007340" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007340</a>]</span><br /> -
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Ataxic gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br /> -
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Scissoring gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22090007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22090007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231698&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231698</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012407</a>]</span><br /> -
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Brisk deep tendon reflexes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673700&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673700</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001348</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001348" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001348</a>]</span><br /> -
|
|
Positive Babinski sign, bilateral <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227528&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227528</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
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Clonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36649002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36649002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009024&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009024</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002169" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002169</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002169" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002169</a>]</span><br /> -
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Dystonia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
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Spasticity of lower extremities (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/394679006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">394679006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1271100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1271100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002061" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002061</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002061" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002061</a>]</span><br /> -
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Spastic diplegia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/281411007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">281411007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G80.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G80.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023882&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023882</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001264" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001264</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001264" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001264</a>]</span><br /> -
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Spastic quadriplegia (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192965001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192965001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426970&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426970</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002510</a>]</span><br /> -
|
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Cerebral atrophy, mild diffuse <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856551&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856551</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
|
|
Cerebellar volume loss, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227525</a>]</span><br /> -
|
|
Wallerian degeneration of cerebral peduncles (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227524&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227524</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>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> METABOLIC FEATURES </strong>
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|
</span>
|
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Hypoglycemia, intermittent severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013228&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013228</a>]</span><br /> -
|
|
Metabolic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59455009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59455009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220981</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span><br /> -
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Lactic acidemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/190882007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">190882007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0347959&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0347959</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
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Excretion of dicarboxylic acids <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227510</a>]</span><br /> -
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Normalization of metabolic parameters in between crises <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227509&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227509</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>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> ENDOCRINE FEATURES </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Elevated TSH <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/309080005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">309080005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0586553&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0586553</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002925" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002925</a>]</span><br /> -
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Hypothyroidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40930008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40930008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E03.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E03.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/244.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">244.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020676</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000821" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000821</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000821" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000821</a>]</span><br /> -
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Premature pubarche (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237815000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237815000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0342541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0342541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012411" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012411</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012411" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012411</a>]</span><br />
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Hypoglycemia, intermittent severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013228&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013228</a>]</span><br /> -
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Myoglobinuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48165008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48165008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R82.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R82.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/791.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">791.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027080&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027080</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002913" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002913</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002913" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002913</a>]</span><br /> -
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Ketonuria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36815008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36815008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274783007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274783007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R82.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R82.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/791.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">791.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162275&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162275</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002919</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002919" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002919</a>]</span><br /> -
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Elevated serum creatine phosphokinase (CPK) levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227517&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227517</a>]</span><br /> -
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Elevated serum ammonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740942&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740942</a>]</span><br /> -
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Elevated serum transaminases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0438717&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0438717</a>, <a href="https://bioportal.bioontology.org/search?q=C0859350&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0859350</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
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Elevated serum acylcarnitines <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227516&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227516</a>]</span><br /> -
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Elevated aldolase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227515&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227515</a>]</span><br />
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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<div style="margin-left: 2em;">
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- Metabolic encephalomyopathic crises often triggered by infection<br />
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Caused by mutation in the transport and Golgi organization 2 homolog gene (TANGO2, <a href="/entry/616830#0001">616830.0001</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is caused by homozygous or compound heterozygous mutation in the TANGO2 gene (<a href="/entry/616830">616830</a>) on chromosome 22q11.</p>
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Description</strong>
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<p>Recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is an autosomal recessive disorder characterized by episodic metabolic degeneration affecting skeletal muscle, cardiac muscle, and the nervous system. Affected individuals usually present in childhood with acute encephalomyopathic features, including rhabdomyolysis, hypotonia, and neurologic regression, although most patients have delayed psychomotor development before the acute onset. The overall disease course is characterized by progressive neurodegeneration with epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Cardiac involvement with severe arrhythmias is a consistent and potentially life-threatening manifestation (summary by <a href="#7" class="mim-tip-reference" title="Lalani, S. R., Liu, P., Rosenfeld, J. A., Watkin, L. B., Chiang, T., Leduc, M. S., Zhu, W., Ding, Y., Pan, S., Vetrini, F., Miyake, C. Y., Shinawi, M., and 39 others. <strong>Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations.</strong> Am. J. Hum. Genet. 98: 347-357, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805781[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/10.1016/j.ajhg.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805781">Lalani et al., 2016</a> and <a href="#6" class="mim-tip-reference" title="Kremer, L. S., Distelmaier, F., Alhaddad, B., Hempel, M., Iuso, A., Kupper, C., Muhlhausen, C., Kovacs-Nagy, R., Satanovskij, R., Graf, E., Berutti, R., Eckstein, G., and 9 others. <strong>Biallelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy.</strong> Am. J. Hum. Genet. 98: 358-362, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805782[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/10.1016/j.ajhg.2015.12.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805782">Kremer et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26805781+26805782" 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>Clinical Features</strong>
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<p><a href="#7" class="mim-tip-reference" title="Lalani, S. R., Liu, P., Rosenfeld, J. A., Watkin, L. B., Chiang, T., Leduc, M. S., Zhu, W., Ding, Y., Pan, S., Vetrini, F., Miyake, C. Y., Shinawi, M., and 39 others. <strong>Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations.</strong> Am. J. Hum. Genet. 98: 347-357, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805781[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/10.1016/j.ajhg.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805781">Lalani et al. (2016)</a> studied 12 affected individuals from 9 families with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to cardiac tachyarrhythmias. Acute rhabdomyolysis was the presentation in 10 of the 12 patients, with onset between 5 months and 8 years of age. Neurodevelopmental problems were observed in all affected individuals by early childhood, and muscle weakness, gait abnormality, or poor coordination were reported in most patients prior to the acute presentation of myoglobinuria. Seizures were present in 9 of 12 patients. The acute clinical presentation ranged from profound muscle weakness, ataxia, and/or disorientation to a comatose state, frequently precipitated by an acute illness. During these metabolic crises, hypoglycemia, hyperlactacidemia, and mild hyperammonemia were repeatedly observed. Elevated transaminases were also noted, indicative of muscle injury. Acylcarnitine profiles during acute episodes showed elevated C14:1 in at least 3 patients; another patient had elevated C10 species during the acute episode, and another showed elevated C3 (propionyl-carnitine) and C10 species. Life-threatening cardiac tachyarrhythmia presented as torsade de pointes or ventricular tachycardia in 4 (33%) of 12 patients, and intermittent prolonged QTc interval was seen in 6 (50%) of patients. The QT interval often reverted to normal between episodes, and metabolic abnormalities typically normalized outside the critical period of crises. Mitochondrial studies and muscle biopsies were essentially normal. Structural brain abnormalities, seen in 7 of 10 patients who underwent imaging, mostly reflected varying degrees of cerebral atrophy or volume loss. Gait disturbances, dysarthria, and myopathic facies were observed in most patients outside the crisis episodes. Hypothyroidism was diagnosed in 4 of 12 patients. In 1 family, affected twins from a dichorionic diamniotic pregnancy died at 2 years of age, the boy during an episode of hypoglycemia and lactic acidemia, and the girl due to worsening cardiomyopathy. In another family, 1 sib from an affected monozygotic twin pair died at 7 years of age during an acute rhabdomyolytic crisis, whereas his twin brother was alive at 11 years of age. The oldest living patient in the study cohort was 27. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Kremer, L. S., Distelmaier, F., Alhaddad, B., Hempel, M., Iuso, A., Kupper, C., Muhlhausen, C., Kovacs-Nagy, R., Satanovskij, R., Graf, E., Berutti, R., Eckstein, G., and 9 others. <strong>Biallelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy.</strong> Am. J. Hum. Genet. 98: 358-362, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805782[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/10.1016/j.ajhg.2015.12.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805782">Kremer et al. (2016)</a> reported 3 unrelated individuals with recurrent encephalomyopathic crises characterized by hypoglycemia, elevated plasma creatine kinase activity, lactic acidosis, and increased acylcarnitines, as well as massive urinary excretion of lactate, ketones, and dicarboxylic acids. Prior to the first crisis, global developmental delay as well as cortical signs were observed. Although the clinical condition stabilized between episodes, the overall disease course was one of neurodegeneration, including epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Optic atrophy and sensorineural hearing impairment were each seen in 1 patient. Cardiac involvement, with severe arrhythmias including torsade de pointes and long QT syndrome, was a consistent and potentially life-threatening condition. Increased TSH levels indicating hypothyroidism were documented in all 3 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Berat, C. M., Montealegre, S., Wiedemann, A., Nuzum, M. L. C., Blondel, A., Debruge, H., Cano, A., Chabrol, B., Hoebeke, C., Polak, M., Stoupa, A., Feillet, F., and 19 others. <strong>Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.</strong> J. Inherit. Metab. Dis. 44: 415-425, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32929747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32929747</a>] [<a href="https://doi.org/10.1002/jimd.12314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32929747">Berat et al. (2021)</a> described 20 patients from 14 families with MECRCN. Seventeen patients presented with neurodevelopmental delay, 17 patients presented with neurologic crises, and 12 patients had hypothyroidism. Symptoms were variable within families. Acute metabolic decompensations included rhabdomyolysis in 15 patients, acute neurologic symptoms in 14, cardiac symptoms in 12, hypoglycemia in 5, and muscle weakness in 7. Three patients (P10, P14, P16) did not have metabolic crises. Laboratory testing demonstrated an abnormal acylcarnitine profile in 2 patients (P13 and P17) with increased C5OH and C4DC, and an initial increase in medium chains that subsequently normalized, respectively. Urine organic acids demonstrated increased lactate and dicarboxylic acids in 1 patient (P6) during a metabolic crisis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32929747" 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="Jennions, E., Hedberg-Oldfors, C., Berglund, A. K., Kollberg, G., Tornhage, C. J., Eklund, E. A., Oldfors, A., Verloo, P., Vanlander, A. V., De Meirleir, L., Seneca, S., Sterky, F. H., Darin, N. <strong>TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism.</strong> J. Inherit. Metab. Dis. 42: 898-908, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31276219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31276219</a>] [<a href="https://doi.org/10.1002/jimd.12149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31276219">Jennions et al. (2019)</a> described 11 patients from 7 families with developmental delay, ataxia, dysarthria, intellectual disability, or spastic diplegia. Nine of the patients experienced episodes of metabolic crisis, whereas 2 patients, aged 12 and 17 years, never experienced a metabolic crisis. Four of 6 patients for whom complex II activity was tested showed mildly reduced activity that appeared to correlate to proximity to a metabolic crisis. Brain tissue from one deceased patient (F1:II:1) demonstrated moderate gliosis of white matter and heterotopic neurons in the cerebral white matter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31276219" 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="Dines, J. N., Golden-Grant, K., LaCroix, A., Muir, A. M., Cintron, D. L., McWalter, K., Cho, M. T., Sun, A., Merritt, J. L., Thies, J., Niyazov, D., Burton, B., and 20 others. <strong>TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.</strong> Genet. Med. 21: 601-607, 2019. Note: Erratum: Genet. Med. 21: 1899, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30245509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30245509</a>] [<a href="https://doi.org/10.1038/s41436-018-0137-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30245509">Dines et al. (2019)</a> described 14 patients from 11 families with MECRCN. Onset of symptoms ranged from 4 to 27 months, with developmental delay as the most common initial feature. Neurologic features included seizures in 10 patients, cerebral atrophy in 5, developmental delay in 12, and neurologic regression in 6. Laboratory findings during metabolic crises included hypoglycemia in 9, hyperammonemia in 3, elevated lactate in 8, and elevated creatine kinase in 11. Eight patients had feeding difficulties necessitating G-tube placement, and 6 patients had gastrointestinal dysmotility. Cardiac findings included electrocardiogram abnormalities in 6 patients during metabolic crises; 3 patients had a cardiac arrest. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30245509" 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="Mingirulli, N., Pyle, A., Hathazi, D., Alston, C. L., Kohlschmidt, N., O'Grady, G., Waddell, L., Evesson, F., Cooper, S. B. T., Turner, C., Duff, J., Topf, A., and 31 others. <strong>Clinical presentation and proteomic signature of patients with TANGO2 mutations.</strong> J. Inherit. Metab. Dis. 43: 297-308, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31339582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31339582</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31339582[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/10.1002/jimd.12156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31339582">Mingirulli et al. (2020)</a> reported 9 patients from 7 families with MECRN who presented with similar symptoms, including neurodevelopmental decline and recurrent metabolic crises. Two of the patients were small for gestation age and had microcephaly at birth. Biochemical findings during acute crises included elevated creatine kinase and hyperammonemia. Two patients had hypoglycemia, and 4 patients had nonspecific elevations in acylcarnitines and dicarboxylic acids. Muscle biopsy was performed in 5 patients, which showed variable regenerative and degenerative changes, consistent with a history of rhabdomyolysis. Coenzyme Q10 levels were reduced in muscle tissue from 2 patients, and individual respiratory chain enzymes were variably affected across the patient samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31339582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Frey, J., Burns, M. R., Chiu, S. Y., Wagle Shukla, A., El Kouzi, A., Jackson, J., Arn, P. H., Malaty, I. A. <strong>TANGO2 Mutation: A Genetic Cause of Multifocal Combined Dystonia.</strong> Mov. Disord. Clin. Pract. 9: 380-382, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35402644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35402644</a>] [<a href="https://doi.org/10.1002/mdc3.13400" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35402644">Frey et al. (2022)</a> reported a 27-year-old woman with MECRCN who had episodes of weakness and recurrent episodes of rhabdomyolysis in infancy and childhood, respectively. At 14 years of age she had a position-dependent wrist tremor, and at 19 years of age she had a gait imbalance. On examination at 27 years of age, she had dystonic posturing of the left arm and both legs, dysarthric speech, dysconjugate gaze, and facial hypotonia. Brain MRI and EEG were unremarkable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35402644" 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="Sen, K., Hicks, M. A., Huq, A. H. M., Agarwal, R. <strong>Homozygous TANGO2 single nucleotide variants presenting with additional manifestations resembling alternating hemiplegia of childhood--expanding the phenotype of a recently reported condition.</strong> Neuropediatrics 50: 122-125, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30650451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30650451</a>] [<a href="https://doi.org/10.1055/s-0038-1677514" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30650451">Sen et al. (2019)</a> reported a 15-year-old patient with MECRCN who had a history of developmental regression and unstable gait and development of partial complex seizures at 3 years of age. At 5 years of age she developed episodes of unilateral paralysis during infections or exposure to cold which resolved with sleep. She also had intermittent dystonic episodes of her lower extremities. Brain MRI showed nonspecific hyperintensities in the posterior pons and subcortical white matter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30650451" 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="#7" class="mim-tip-reference" title="Lalani, S. R., Liu, P., Rosenfeld, J. A., Watkin, L. B., Chiang, T., Leduc, M. S., Zhu, W., Ding, Y., Pan, S., Vetrini, F., Miyake, C. Y., Shinawi, M., and 39 others. <strong>Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations.</strong> Am. J. Hum. Genet. 98: 347-357, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805781[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/10.1016/j.ajhg.2015.12.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805781">Lalani et al. (2016)</a> performed whole-exome sequencing in 12 patients from 9 families with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, who were negative for mutation in rhabdomyolysis-associated genes. A recurrent homozygous missense mutation in the TANGO2 gene (G154R; <a href="/entry/616830#0001">616830.0001</a>) was identified in 4 unrelated Hispanic probands, and homozygous deletion of exons 3-9 (<a href="/entry/616830#0002">616830.0002</a>) was identified in 4 probands from 2 families of European origin. In addition, the proband from a mixed Hispanic/European family was compound heterozygous for G154R and the exon 3-9 deletion. In another Hispanic family, the proband was homozygous for a splice site mutation (<a href="/entry/616830#0003">616830.0003</a>), and 2 affected sibs from a Saudi Arabian family carried a homozygous deletion of exons 4-6 (<a href="/entry/616830#0004">616830.0004</a>). The mutations segregated fully with disease in the families, and none of the variants was present in homozygosity in control databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Kremer, L. S., Distelmaier, F., Alhaddad, B., Hempel, M., Iuso, A., Kupper, C., Muhlhausen, C., Kovacs-Nagy, R., Satanovskij, R., Graf, E., Berutti, R., Eckstein, G., and 9 others. <strong>Biallelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy.</strong> Am. J. Hum. Genet. 98: 358-362, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805782[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/10.1016/j.ajhg.2015.12.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26805782">Kremer et al. (2016)</a> performed whole-exome sequencing in 3 unrelated individuals with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, and identified homozygosity or compound heterozygosity for mutations in the TANGO2 gene in all 3 patients: 1 patient was homozygous for deletion of exons 3-9, another was compound heterozygous for the exon 3-9 deletion and a 1-bp deletion (<a href="/entry/616830#0005">616830.0005</a>), and the third patient was homozygous for a nonsense mutation (R140X; <a href="/entry/616830#0006">616830.0006</a>). The mutations segregated with disease in each of the families, and none of the variants had been reported in homozygous state in public databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805782" 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 11 patients from 7 families, including 4 sib pairs, with MECRCN, <a href="#5" class="mim-tip-reference" title="Jennions, E., Hedberg-Oldfors, C., Berglund, A. K., Kollberg, G., Tornhage, C. J., Eklund, E. A., Oldfors, A., Verloo, P., Vanlander, A. V., De Meirleir, L., Seneca, S., Sterky, F. H., Darin, N. <strong>TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism.</strong> J. Inherit. Metab. Dis. 42: 898-908, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31276219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31276219</a>] [<a href="https://doi.org/10.1002/jimd.12149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31276219">Jennions et al. (2019)</a> identified biallelic mutations in the TANGO2 gene (see <a href="/entry/616830#0002">616830.0002</a>; <a href="/entry/616830#0004">616830.0004</a>; <a href="/entry/616830#0007">616830.0007</a>-<a href="/entry/616830#0010">616830.0010</a>). The most common mutation, deletion of exons 3-9 (<a href="/entry/616830#0002">616830.0002</a>) was found in 5 patients from 3 families. All of the mutations were absent or extremely rare (less than 0.002%) in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31276219" 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="Dines, J. N., Golden-Grant, K., LaCroix, A., Muir, A. M., Cintron, D. L., McWalter, K., Cho, M. T., Sun, A., Merritt, J. L., Thies, J., Niyazov, D., Burton, B., and 20 others. <strong>TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.</strong> Genet. Med. 21: 601-607, 2019. Note: Erratum: Genet. Med. 21: 1899, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30245509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30245509</a>] [<a href="https://doi.org/10.1038/s41436-018-0137-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30245509">Dines et al. (2019)</a> reported 14 patients from 11 families, including a sib pair and a sib trio, with MECRCN and biallelic mutations in the TANGO2 gene. The most common mutation was the exon 3-9 deletion (<a href="/entry/616830#0002">616830.0002</a>), which was homozygous in 5 families and compound heterozygous in 4 families. The other mutations included a splice site mutation (<a href="/entry/616830#0009">616830.0009</a>), a nonsense mutation (R32X), an exon 6 deletion, and 2 missense mutations (R26K; G89C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30245509" 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="Mingirulli, N., Pyle, A., Hathazi, D., Alston, C. L., Kohlschmidt, N., O'Grady, G., Waddell, L., Evesson, F., Cooper, S. B. T., Turner, C., Duff, J., Topf, A., and 31 others. <strong>Clinical presentation and proteomic signature of patients with TANGO2 mutations.</strong> J. Inherit. Metab. Dis. 43: 297-308, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31339582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31339582</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31339582[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/10.1002/jimd.12156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31339582">Mingirulli et al. (2020)</a> identified biallelic mutations in the TANGO2 gene in 9 patients from 7 families with MECRCN and performed functional studies and proteomic analysis in fibroblasts from a subset of this cohort. In fibroblasts from 2 patients, studies of Golgi apparatus disassembly after treatment with brefeldin A suggested delayed disassembly and possible dysfunction of retrograde Golgi-endoplasmic reticulum (ER) trafficking. Proteomics analysis of fibroblasts from 3 of the patients showed dysregulation of pathways involved in the ER-Golgi network, the plasma membrane and mitochondria, and in the secretory pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31339582" 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 20 patients from 14 families with MECRCN, <a href="#1" class="mim-tip-reference" title="Berat, C. M., Montealegre, S., Wiedemann, A., Nuzum, M. L. C., Blondel, A., Debruge, H., Cano, A., Chabrol, B., Hoebeke, C., Polak, M., Stoupa, A., Feillet, F., and 19 others. <strong>Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.</strong> J. Inherit. Metab. Dis. 44: 415-425, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32929747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32929747</a>] [<a href="https://doi.org/10.1002/jimd.12314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32929747">Berat et al. (2021)</a> identified homozygous (13 patients) or compound heterozygous (7 patients) mutations in the TANGO2 gene. The mutations included 7 point mutations (5 of which were novel), 2 small deletions, and 1 exon 3-9 deletion. Oxidation of palmitate and glutamate were measured in myoblasts from 2 patients (patients 11 and 18) and did not demonstrate an abnormality in the Krebs cycle or in mitochondrial fatty acid oxidation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32929747" 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="Heiman, P., Mohsen, A. W., Karunanidhi, A., St Croix, C., Watkins, S., Koppes, E., Haas, R., Vockley, J., Ghaloul-Gonzalez, L. <strong>Mitochondrial dysfunction associated with TANGO2 deficiency.</strong> Sci. Rep. 12: 3045, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35197517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35197517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35197517[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/10.1038/s41598-022-07076-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35197517">Heiman et al. (2022)</a> identified biallelic mutations in the TANGO2 gene in 3 individuals, including a sib pair, with MECRCN. The sibs (patients 1 and 2) were homozygous for the deletion of exons 3-9, and patient 3 was compound heterozygous for the exon 3-9 deletion and a splice site mutation (c.605+1G-A). TANGO2 protein expression was absent in fibroblasts from all 3 patients, whereas it was present in whole cell extracts and mitochondrial cellular fractions in control fibroblasts. ATP content was significantly decreased, and reduced oleate flux through fatty acid oxidation was demonstrated in patient fibroblasts. Mitochondrial volume, mtDNA, and oxygen consumption rates were also decreased in patient fibroblasts compared to controls. <a href="#4" class="mim-tip-reference" title="Heiman, P., Mohsen, A. W., Karunanidhi, A., St Croix, C., Watkins, S., Koppes, E., Haas, R., Vockley, J., Ghaloul-Gonzalez, L. <strong>Mitochondrial dysfunction associated with TANGO2 deficiency.</strong> Sci. Rep. 12: 3045, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35197517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35197517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35197517[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/10.1038/s41598-022-07076-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35197517">Heiman et al. (2022)</a> concluded that these results indicate broad mitochondrial dysfunction in MECRCN. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35197517" 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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Berat, C. M., Montealegre, S., Wiedemann, A., Nuzum, M. L. C., Blondel, A., Debruge, H., Cano, A., Chabrol, B., Hoebeke, C., Polak, M., Stoupa, A., Feillet, F., and 19 others.
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<strong>Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.</strong>
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J. Inherit. Metab. Dis. 44: 415-425, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32929747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32929747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32929747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/jimd.12314" target="_blank">Full Text</a>]
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Dines, J. N., Golden-Grant, K., LaCroix, A., Muir, A. M., Cintron, D. L., McWalter, K., Cho, M. T., Sun, A., Merritt, J. L., Thies, J., Niyazov, D., Burton, B., and 20 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30245509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30245509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30245509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41436-018-0137-y" target="_blank">Full Text</a>]
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Frey, J., Burns, M. R., Chiu, S. Y., Wagle Shukla, A., El Kouzi, A., Jackson, J., Arn, P. H., Malaty, I. A.
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<strong>TANGO2 Mutation: A Genetic Cause of Multifocal Combined Dystonia.</strong>
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Mov. Disord. Clin. Pract. 9: 380-382, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35402644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35402644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35402644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/mdc3.13400" target="_blank">Full Text</a>]
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Heiman, P., Mohsen, A. W., Karunanidhi, A., St Croix, C., Watkins, S., Koppes, E., Haas, R., Vockley, J., Ghaloul-Gonzalez, L.
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<strong>Mitochondrial dysfunction associated with TANGO2 deficiency.</strong>
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Sci. Rep. 12: 3045, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35197517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35197517</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35197517[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35197517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41598-022-07076-9" target="_blank">Full Text</a>]
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Jennions, E., Hedberg-Oldfors, C., Berglund, A. K., Kollberg, G., Tornhage, C. J., Eklund, E. A., Oldfors, A., Verloo, P., Vanlander, A. V., De Meirleir, L., Seneca, S., Sterky, F. H., Darin, N.
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<strong>TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism.</strong>
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J. Inherit. Metab. Dis. 42: 898-908, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31276219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31276219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31276219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/jimd.12149" target="_blank">Full Text</a>]
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Kremer, L. S., Distelmaier, F., Alhaddad, B., Hempel, M., Iuso, A., Kupper, C., Muhlhausen, C., Kovacs-Nagy, R., Satanovskij, R., Graf, E., Berutti, R., Eckstein, G., and 9 others.
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<strong>Biallelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy.</strong>
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Am. J. Hum. Genet. 98: 358-362, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805782[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2015.12.009" target="_blank">Full Text</a>]
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Lalani, S. R., Liu, P., Rosenfeld, J. A., Watkin, L. B., Chiang, T., Leduc, M. S., Zhu, W., Ding, Y., Pan, S., Vetrini, F., Miyake, C. Y., Shinawi, M., and 39 others.
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<strong>Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26805781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26805781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26805781[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26805781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2015.12.008" target="_blank">Full Text</a>]
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Mingirulli, N., Pyle, A., Hathazi, D., Alston, C. L., Kohlschmidt, N., O'Grady, G., Waddell, L., Evesson, F., Cooper, S. B. T., Turner, C., Duff, J., Topf, A., and 31 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31339582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31339582</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31339582[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31339582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/jimd.12156" target="_blank">Full Text</a>]
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Sen, K., Hicks, M. A., Huq, A. H. M., Agarwal, R.
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<strong>Homozygous TANGO2 single nucleotide variants presenting with additional manifestations resembling alternating hemiplegia of childhood--expanding the phenotype of a recently reported condition.</strong>
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Neuropediatrics 50: 122-125, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30650451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30650451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30650451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1055/s-0038-1677514" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/03/2023
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Hilary J. Vernon - updated : 01/27/2023<br>Cassandra L. Kniffin - updated : 05/07/2019
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carol : 01/27/2023<br>carol : 05/09/2019<br>ckniffin : 05/07/2019<br>alopez : 08/08/2017<br>alopez : 03/23/2016
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<strong>#</strong> 616878
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METABOLIC CRISES, RECURRENT, WITH RHABDOMYOLYSIS, CARDIAC ARRHYTHMIAS, AND NEURODEGENERATION; MECRCN
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<strong>SNOMEDCT:</strong> 1172698005;
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<strong>ORPHA:</strong> 480864;
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<strong>DO:</strong> 0081386;
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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 <br /> MIM number
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22q11.21
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Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
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616878
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Autosomal recessive
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3
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TANGO2
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<span class="mim-font">
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616830
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<p>A number sign (#) is used with this entry because of evidence that recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is caused by homozygous or compound heterozygous mutation in the TANGO2 gene (616830) on chromosome 22q11.</p>
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<strong>Description</strong>
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<p>Recurrent metabolic crises with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) is an autosomal recessive disorder characterized by episodic metabolic degeneration affecting skeletal muscle, cardiac muscle, and the nervous system. Affected individuals usually present in childhood with acute encephalomyopathic features, including rhabdomyolysis, hypotonia, and neurologic regression, although most patients have delayed psychomotor development before the acute onset. The overall disease course is characterized by progressive neurodegeneration with epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Cardiac involvement with severe arrhythmias is a consistent and potentially life-threatening manifestation (summary by Lalani et al., 2016 and Kremer et al., 2016). </p>
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<p>Lalani et al. (2016) studied 12 affected individuals from 9 families with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to cardiac tachyarrhythmias. Acute rhabdomyolysis was the presentation in 10 of the 12 patients, with onset between 5 months and 8 years of age. Neurodevelopmental problems were observed in all affected individuals by early childhood, and muscle weakness, gait abnormality, or poor coordination were reported in most patients prior to the acute presentation of myoglobinuria. Seizures were present in 9 of 12 patients. The acute clinical presentation ranged from profound muscle weakness, ataxia, and/or disorientation to a comatose state, frequently precipitated by an acute illness. During these metabolic crises, hypoglycemia, hyperlactacidemia, and mild hyperammonemia were repeatedly observed. Elevated transaminases were also noted, indicative of muscle injury. Acylcarnitine profiles during acute episodes showed elevated C14:1 in at least 3 patients; another patient had elevated C10 species during the acute episode, and another showed elevated C3 (propionyl-carnitine) and C10 species. Life-threatening cardiac tachyarrhythmia presented as torsade de pointes or ventricular tachycardia in 4 (33%) of 12 patients, and intermittent prolonged QTc interval was seen in 6 (50%) of patients. The QT interval often reverted to normal between episodes, and metabolic abnormalities typically normalized outside the critical period of crises. Mitochondrial studies and muscle biopsies were essentially normal. Structural brain abnormalities, seen in 7 of 10 patients who underwent imaging, mostly reflected varying degrees of cerebral atrophy or volume loss. Gait disturbances, dysarthria, and myopathic facies were observed in most patients outside the crisis episodes. Hypothyroidism was diagnosed in 4 of 12 patients. In 1 family, affected twins from a dichorionic diamniotic pregnancy died at 2 years of age, the boy during an episode of hypoglycemia and lactic acidemia, and the girl due to worsening cardiomyopathy. In another family, 1 sib from an affected monozygotic twin pair died at 7 years of age during an acute rhabdomyolytic crisis, whereas his twin brother was alive at 11 years of age. The oldest living patient in the study cohort was 27. </p><p>Kremer et al. (2016) reported 3 unrelated individuals with recurrent encephalomyopathic crises characterized by hypoglycemia, elevated plasma creatine kinase activity, lactic acidosis, and increased acylcarnitines, as well as massive urinary excretion of lactate, ketones, and dicarboxylic acids. Prior to the first crisis, global developmental delay as well as cortical signs were observed. Although the clinical condition stabilized between episodes, the overall disease course was one of neurodegeneration, including epilepsy, cognitive impairment, pyramidal and cerebellar signs, and loss of expressive language. Optic atrophy and sensorineural hearing impairment were each seen in 1 patient. Cardiac involvement, with severe arrhythmias including torsade de pointes and long QT syndrome, was a consistent and potentially life-threatening condition. Increased TSH levels indicating hypothyroidism were documented in all 3 patients. </p><p>Berat et al. (2021) described 20 patients from 14 families with MECRCN. Seventeen patients presented with neurodevelopmental delay, 17 patients presented with neurologic crises, and 12 patients had hypothyroidism. Symptoms were variable within families. Acute metabolic decompensations included rhabdomyolysis in 15 patients, acute neurologic symptoms in 14, cardiac symptoms in 12, hypoglycemia in 5, and muscle weakness in 7. Three patients (P10, P14, P16) did not have metabolic crises. Laboratory testing demonstrated an abnormal acylcarnitine profile in 2 patients (P13 and P17) with increased C5OH and C4DC, and an initial increase in medium chains that subsequently normalized, respectively. Urine organic acids demonstrated increased lactate and dicarboxylic acids in 1 patient (P6) during a metabolic crisis. </p><p>Jennions et al. (2019) described 11 patients from 7 families with developmental delay, ataxia, dysarthria, intellectual disability, or spastic diplegia. Nine of the patients experienced episodes of metabolic crisis, whereas 2 patients, aged 12 and 17 years, never experienced a metabolic crisis. Four of 6 patients for whom complex II activity was tested showed mildly reduced activity that appeared to correlate to proximity to a metabolic crisis. Brain tissue from one deceased patient (F1:II:1) demonstrated moderate gliosis of white matter and heterotopic neurons in the cerebral white matter. </p><p>Dines et al. (2019) described 14 patients from 11 families with MECRCN. Onset of symptoms ranged from 4 to 27 months, with developmental delay as the most common initial feature. Neurologic features included seizures in 10 patients, cerebral atrophy in 5, developmental delay in 12, and neurologic regression in 6. Laboratory findings during metabolic crises included hypoglycemia in 9, hyperammonemia in 3, elevated lactate in 8, and elevated creatine kinase in 11. Eight patients had feeding difficulties necessitating G-tube placement, and 6 patients had gastrointestinal dysmotility. Cardiac findings included electrocardiogram abnormalities in 6 patients during metabolic crises; 3 patients had a cardiac arrest. </p><p>Mingirulli et al. (2020) reported 9 patients from 7 families with MECRN who presented with similar symptoms, including neurodevelopmental decline and recurrent metabolic crises. Two of the patients were small for gestation age and had microcephaly at birth. Biochemical findings during acute crises included elevated creatine kinase and hyperammonemia. Two patients had hypoglycemia, and 4 patients had nonspecific elevations in acylcarnitines and dicarboxylic acids. Muscle biopsy was performed in 5 patients, which showed variable regenerative and degenerative changes, consistent with a history of rhabdomyolysis. Coenzyme Q10 levels were reduced in muscle tissue from 2 patients, and individual respiratory chain enzymes were variably affected across the patient samples. </p><p>Frey et al. (2022) reported a 27-year-old woman with MECRCN who had episodes of weakness and recurrent episodes of rhabdomyolysis in infancy and childhood, respectively. At 14 years of age she had a position-dependent wrist tremor, and at 19 years of age she had a gait imbalance. On examination at 27 years of age, she had dystonic posturing of the left arm and both legs, dysarthric speech, dysconjugate gaze, and facial hypotonia. Brain MRI and EEG were unremarkable. </p><p>Sen et al. (2019) reported a 15-year-old patient with MECRCN who had a history of developmental regression and unstable gait and development of partial complex seizures at 3 years of age. At 5 years of age she developed episodes of unilateral paralysis during infections or exposure to cold which resolved with sleep. She also had intermittent dystonic episodes of her lower extremities. Brain MRI showed nonspecific hyperintensities in the posterior pons and subcortical white matter. </p>
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<strong>Molecular Genetics</strong>
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<p>Lalani et al. (2016) performed whole-exome sequencing in 12 patients from 9 families with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, who were negative for mutation in rhabdomyolysis-associated genes. A recurrent homozygous missense mutation in the TANGO2 gene (G154R; 616830.0001) was identified in 4 unrelated Hispanic probands, and homozygous deletion of exons 3-9 (616830.0002) was identified in 4 probands from 2 families of European origin. In addition, the proband from a mixed Hispanic/European family was compound heterozygous for G154R and the exon 3-9 deletion. In another Hispanic family, the proband was homozygous for a splice site mutation (616830.0003), and 2 affected sibs from a Saudi Arabian family carried a homozygous deletion of exons 4-6 (616830.0004). The mutations segregated fully with disease in the families, and none of the variants was present in homozygosity in control databases. </p><p>Kremer et al. (2016) performed whole-exome sequencing in 3 unrelated individuals with recurrent metabolic encephalomyopathic crises associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, and identified homozygosity or compound heterozygosity for mutations in the TANGO2 gene in all 3 patients: 1 patient was homozygous for deletion of exons 3-9, another was compound heterozygous for the exon 3-9 deletion and a 1-bp deletion (616830.0005), and the third patient was homozygous for a nonsense mutation (R140X; 616830.0006). The mutations segregated with disease in each of the families, and none of the variants had been reported in homozygous state in public databases. </p><p>In 11 patients from 7 families, including 4 sib pairs, with MECRCN, Jennions et al. (2019) identified biallelic mutations in the TANGO2 gene (see 616830.0002; 616830.0004; 616830.0007-616830.0010). The most common mutation, deletion of exons 3-9 (616830.0002) was found in 5 patients from 3 families. All of the mutations were absent or extremely rare (less than 0.002%) in the gnomAD database. </p><p>Dines et al. (2019) reported 14 patients from 11 families, including a sib pair and a sib trio, with MECRCN and biallelic mutations in the TANGO2 gene. The most common mutation was the exon 3-9 deletion (616830.0002), which was homozygous in 5 families and compound heterozygous in 4 families. The other mutations included a splice site mutation (616830.0009), a nonsense mutation (R32X), an exon 6 deletion, and 2 missense mutations (R26K; G89C). </p><p>Mingirulli et al. (2020) identified biallelic mutations in the TANGO2 gene in 9 patients from 7 families with MECRCN and performed functional studies and proteomic analysis in fibroblasts from a subset of this cohort. In fibroblasts from 2 patients, studies of Golgi apparatus disassembly after treatment with brefeldin A suggested delayed disassembly and possible dysfunction of retrograde Golgi-endoplasmic reticulum (ER) trafficking. Proteomics analysis of fibroblasts from 3 of the patients showed dysregulation of pathways involved in the ER-Golgi network, the plasma membrane and mitochondria, and in the secretory pathway. </p><p>In 20 patients from 14 families with MECRCN, Berat et al. (2021) identified homozygous (13 patients) or compound heterozygous (7 patients) mutations in the TANGO2 gene. The mutations included 7 point mutations (5 of which were novel), 2 small deletions, and 1 exon 3-9 deletion. Oxidation of palmitate and glutamate were measured in myoblasts from 2 patients (patients 11 and 18) and did not demonstrate an abnormality in the Krebs cycle or in mitochondrial fatty acid oxidation. </p><p>Heiman et al. (2022) identified biallelic mutations in the TANGO2 gene in 3 individuals, including a sib pair, with MECRCN. The sibs (patients 1 and 2) were homozygous for the deletion of exons 3-9, and patient 3 was compound heterozygous for the exon 3-9 deletion and a splice site mutation (c.605+1G-A). TANGO2 protein expression was absent in fibroblasts from all 3 patients, whereas it was present in whole cell extracts and mitochondrial cellular fractions in control fibroblasts. ATP content was significantly decreased, and reduced oleate flux through fatty acid oxidation was demonstrated in patient fibroblasts. Mitochondrial volume, mtDNA, and oxygen consumption rates were also decreased in patient fibroblasts compared to controls. Heiman et al. (2022) concluded that these results indicate broad mitochondrial dysfunction in MECRCN. </p>
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<strong>REFERENCES</strong>
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</h4>
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Berat, C. M., Montealegre, S., Wiedemann, A., Nuzum, M. L. C., Blondel, A., Debruge, H., Cano, A., Chabrol, B., Hoebeke, C., Polak, M., Stoupa, A., Feillet, F., and 19 others.
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<strong>Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.</strong>
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J. Inherit. Metab. Dis. 44: 415-425, 2021.
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[PubMed: 32929747]
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[Full Text: https://doi.org/10.1002/jimd.12314]
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Dines, J. N., Golden-Grant, K., LaCroix, A., Muir, A. M., Cintron, D. L., McWalter, K., Cho, M. T., Sun, A., Merritt, J. L., Thies, J., Niyazov, D., Burton, B., and 20 others.
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<strong>TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants.</strong>
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Genet. Med. 21: 601-607, 2019. Note: Erratum: Genet. Med. 21: 1899, 2019.
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[PubMed: 30245509]
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[Full Text: https://doi.org/10.1038/s41436-018-0137-y]
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Frey, J., Burns, M. R., Chiu, S. Y., Wagle Shukla, A., El Kouzi, A., Jackson, J., Arn, P. H., Malaty, I. A.
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<strong>TANGO2 Mutation: A Genetic Cause of Multifocal Combined Dystonia.</strong>
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Mov. Disord. Clin. Pract. 9: 380-382, 2022.
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[PubMed: 35402644]
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[Full Text: https://doi.org/10.1002/mdc3.13400]
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Heiman, P., Mohsen, A. W., Karunanidhi, A., St Croix, C., Watkins, S., Koppes, E., Haas, R., Vockley, J., Ghaloul-Gonzalez, L.
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<strong>Mitochondrial dysfunction associated with TANGO2 deficiency.</strong>
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Sci. Rep. 12: 3045, 2022.
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[PubMed: 35197517]
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[Full Text: https://doi.org/10.1038/s41598-022-07076-9]
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Jennions, E., Hedberg-Oldfors, C., Berglund, A. K., Kollberg, G., Tornhage, C. J., Eklund, E. A., Oldfors, A., Verloo, P., Vanlander, A. V., De Meirleir, L., Seneca, S., Sterky, F. H., Darin, N.
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<strong>TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism.</strong>
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J. Inherit. Metab. Dis. 42: 898-908, 2019.
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[PubMed: 31276219]
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[Full Text: https://doi.org/10.1002/jimd.12149]
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</li>
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Kremer, L. S., Distelmaier, F., Alhaddad, B., Hempel, M., Iuso, A., Kupper, C., Muhlhausen, C., Kovacs-Nagy, R., Satanovskij, R., Graf, E., Berutti, R., Eckstein, G., and 9 others.
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<strong>Biallelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy.</strong>
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Am. J. Hum. Genet. 98: 358-362, 2016.
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[PubMed: 26805782]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.12.009]
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<li>
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<p class="mim-text-font">
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Lalani, S. R., Liu, P., Rosenfeld, J. A., Watkin, L. B., Chiang, T., Leduc, M. S., Zhu, W., Ding, Y., Pan, S., Vetrini, F., Miyake, C. Y., Shinawi, M., and 39 others.
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<strong>Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations.</strong>
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Am. J. Hum. Genet. 98: 347-357, 2016.
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[PubMed: 26805781]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.12.008]
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Mingirulli, N., Pyle, A., Hathazi, D., Alston, C. L., Kohlschmidt, N., O'Grady, G., Waddell, L., Evesson, F., Cooper, S. B. T., Turner, C., Duff, J., Topf, A., and 31 others.
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<strong>Clinical presentation and proteomic signature of patients with TANGO2 mutations.</strong>
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J. Inherit. Metab. Dis. 43: 297-308, 2020.
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[PubMed: 31339582]
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[Full Text: https://doi.org/10.1002/jimd.12156]
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Sen, K., Hicks, M. A., Huq, A. H. M., Agarwal, R.
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<strong>Homozygous TANGO2 single nucleotide variants presenting with additional manifestations resembling alternating hemiplegia of childhood--expanding the phenotype of a recently reported condition.</strong>
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Neuropediatrics 50: 122-125, 2019.
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[PubMed: 30650451]
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[Full Text: https://doi.org/10.1055/s-0038-1677514]
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Hilary J. Vernon - updated : 02/03/2023<br>Hilary J. Vernon - updated : 01/27/2023<br>Cassandra L. Kniffin - updated : 05/07/2019
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