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Entry
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- #607459 - SENSORY ATAXIC NEUROPATHY, DYSARTHRIA, AND OPHTHALMOPARESIS; SANDO
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- OMIM
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<p>
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<span class="h4">#607459</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/607459"><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="#inheritance">Inheritance</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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<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-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=SENSORY ATAXIC NEUROPATHY, DYSARTHRIA, AND OPHTHALMOPARESIS" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19794&Typ=Pat" title="Spinocerebellar ataxia with epilepsy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Spinocerebellar ataxia wit… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=22878&Typ=Pat" title="Progressive myoclonic epilepsy type 5" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Progressive myoclonic epil… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10966&Typ=Pat" title="Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Sensory ataxic neuropathy-… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK26471/" 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.diseaseinfosearch.org/x/6505" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="#mimMedlinePlusGeneticsFold" id="mimMedlinePlusGeneticsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Consumer-friendly information about the effects of genetic variation on human health."><span id="mimMedlinePlusGeneticsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>MedlinePlus Genetics</div>
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<div id="mimMedlinePlusGeneticsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/condition/ataxia-neuropathy-spectrum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">Ataxia neuropathy spectrum </a></div><div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/condition/myoclonic-epilepsy-myopathy-sensory-ataxia" title="Myoclonic epilepsy myopathy sensory ataxia" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">Myoclonic epilepsy myopath… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607459[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254881" title="Spinocerebellar ataxia with epilepsy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Spinocerebellar ataxia wit…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=402082" title="Progressive myoclonic epilepsy type 5" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Progressive myoclonic epil…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70595" title="Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Sensory ataxic neuropathy-…</a></div>
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0111276" 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/607459" 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:0111276" 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 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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 699328003, 717266001<br />
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<strong>ORPHA:</strong> 254881, 402082, 70595<br />
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<strong>DO:</strong> 0111276<br />
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">ICD+</a>
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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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607459
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SENSORY ATAXIC NEUROPATHY, DYSARTHRIA, AND OPHTHALMOPARESIS; SANDO
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<h4>
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<span class="mim-font">
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SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE
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</h4>
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Other entities represented in this entry:
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</div>
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|
<div>
|
|
<span class="h3 mim-font">
|
|
SPINOCEREBELLAR ATAXIA WITH EPILEPSY, INCLUDED; SCAE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
EPILEPSY, PROGRESSIVE MYOCLONIC, WITH SENSORY ATAXIC NEUROPATHY, INCLUDED<br />
|
|
EPILEPSY, PROGRESSIVE MYOCLONIC, 5, FORMERLY, INCLUDED; EPM5, FORMERLY, INCLUDED
|
|
</span>
|
|
</div>
|
|
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|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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</div>
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|
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|
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<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/15/498?start=-3&limit=10&highlight=498">
|
|
15q26.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607459"> 607459 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
POLG
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174763"> 174763 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/607459" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/607459" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607459" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Ears </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sensorineural hearing loss <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 /> -
|
|
Vestibular dysfunction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848606&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848606</a>, <a href="https://bioportal.bioontology.org/search?q=C1843865&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843865</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001751</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001756</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001756</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
|
|
Upward gaze paresis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843866&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843866</a>]</span><br /> -
|
|
Blepharoptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Ophthalmoparesis, progressive, external <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843867&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000597" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000597</a>]</span><br /> -
|
|
Cataracts (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dilated cardiomyopathy (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399020009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399020009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195021004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195021004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007193&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007193</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001644" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001644</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001644" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001644</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> ABDOMEN </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> Gastrointestinal </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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|
- Gastroparesis (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235675006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235675006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/196753007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">196753007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K31.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K31.84</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/536.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">536.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152020&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152020</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002578" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002578</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002578" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002578</a>]</span><br /> -
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Intestinal pseudo-obstruction (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235825006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235825006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0021847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004389</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004389</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> MUSCLE, SOFT TISSUES </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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|
- Proximal muscle weakness, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843869&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843869</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249939004</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span><br /> -
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|
Dysarthria <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 /> -
|
|
Ragged red fibers seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3151935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3151935</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003200" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003200</a>]</span><br /> -
|
|
Increased variation in fiber size <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843700&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843700</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003557" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003557</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003557" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003557</a>]</span><br /> -
|
|
Necrotic and atrophic fibers with centralized nuclei <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551962&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551962</a>]</span><br /> -
|
|
Multiple mitochondrial DNA (mtDNA) deletions (in most cases) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277376</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003689</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003689</a>]</span><br /> -
|
|
Decreased activity of cytochrome c oxidase (in most cases) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857357&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857357</a>]</span><br /> -
|
|
Subsarcolemmal accumulations of abnormally shaped mitochondria seen on electron microscopy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276121&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276121</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003548</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
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|
|
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</div>
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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">
|
|
|
|
- Gait ataxia, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843885&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843885</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007240</a>]</span> <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><br /> -
|
|
Ataxia worsens in the dark <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843853&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843853</a>]</span><br /> -
|
|
Positive Romberg sign <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298310004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298310004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240914&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240914</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002403</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002403</a>]</span><br /> -
|
|
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
|
|
Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br /> -
|
|
Myoclonus (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17450006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17450006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/333.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">333.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027066</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span><br /> -
|
|
Migraine <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37796009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37796009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G43.909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G43.909</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G43</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G43.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G43.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/346" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">346</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/346.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">346.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149931&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149931</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002076</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002076" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002076</a>]</span><br /> -
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Seizures (less common) <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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Cognitive impairment, mild <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386805003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386805003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G31.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G31.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1270972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1270972</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br /> -
|
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Bilateral thalamic lesions on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843856&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843856</a>]</span><br /> -
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Cerebellar white matter lesions on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843857&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843857</a>]</span><br /> -
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Atrophic and degenerative changes in the spinal cord <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843858&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843858</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007344</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> Peripheral Nervous System </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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- Sensory ataxic neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843859&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843859</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003434" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003434</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003434" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003434</a>]</span><br /> -
|
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Distal sensory impairment to vibration and proprioception <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843860&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843860</a>]</span><br /> -
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Sensory axonal neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842587&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842587</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003390" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003390</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003390" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003390</a>]</span><br /> -
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Sural nerve biopsy shows loss of large and small myelinated axons <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843861&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843861</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> Behavioral Psychiatric Manifestations </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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- Memory difficulties <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843862</a>]</span><br /> -
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Lack of concentration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60032008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60032008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235198&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235198</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031987</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031987</a>]</span><br /> -
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Withdrawal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2825032&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2825032</a>, <a href="https://bioportal.bioontology.org/search?q=C3812880&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3812880</a>, <a href="https://bioportal.bioontology.org/search?q=C2349954&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2349954</a>]</span><br /> -
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Depression <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78667006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78667006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35489007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35489007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366979004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366979004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255339005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255339005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F34.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F34.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F32.A" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F32.A</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F33.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F33.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0812393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0812393</a>, <a href="https://bioportal.bioontology.org/search?q=C0011581&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011581</a>, <a href="https://bioportal.bioontology.org/search?q=C0460137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0460137</a>, <a href="https://bioportal.bioontology.org/search?q=C1579931&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1579931</a>, <a href="https://bioportal.bioontology.org/search?q=C0344315&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344315</a>, <a href="https://bioportal.bioontology.org/search?q=C4085311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4085311</a>, <a href="https://bioportal.bioontology.org/search?q=C0011570&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011570</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000716</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> LABORATORY ABNORMALITIES </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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- Mildly increased serum lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843874</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002151</a>]</span><br /> -
|
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Mildly increased serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850309&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850309</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008180</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008180</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> MISCELLANEOUS </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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- Young-adult onset (18-30 years) of sensory ataxia<br /> -
|
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Later onset of ophthalmoparesis<br /> -
|
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Highly variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839039</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br />
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</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> MOLECULAR BASIS </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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- Caused by mutation in the DNA polymerase-gamma gene (POLG, <a href="/entry/174763#0002">174763.0002</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 class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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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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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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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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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded DNA polymerase-gamma gene (POLG; <a href="/entry/174763">174763</a>) on chromosome 15q26.</p><p>Recessive mutations in the POLG gene can also cause autosomal recessive progressive external ophthalmoplegia (PEOB; <a href="/entry/258450">258450</a>), which shows overlapping features.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<p>SANDO is an autosomal recessive systemic disorder characterized mainly by adult onset of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) resulting from mitochondrial dysfunction and associated with mtDNA depletion in skeletal muscle and peripheral nerve tissue (<a href="#2" class="mim-tip-reference" title="Fadic, R., Russell, J. A., Vedanarayanan, V. V., Lehar, M., Kuncl, R. W., Johns, D. R. <strong>Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease.</strong> Neurology 49: 239-245, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9222196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9222196</a>] [<a href="https://doi.org/10.1212/wnl.49.1.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9222196">Fadic et al., 1997</a>). The phenotype varies widely, even within the same family, and can include myopathy, seizures, and hearing loss, but the common clinical feature appears to be sensory ataxia (review by <a href="#6" class="mim-tip-reference" title="Milone, M., Massie, R. <strong>Polymerase gamma 1 mutations: clinical correlations.</strong> Neurologist 16: 84-91, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220442</a>] [<a href="https://doi.org/10.1097/NRL.0b013e3181c78a89" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220442">Milone and Massie, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9222196+20220442" 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>Spinocerebellar ataxia with epilepsy (SCAE) is a similar disorder with a higher frequency of migraine headaches and seizures (<a href="#13" class="mim-tip-reference" title="Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., Engelsen, B. A., Moen, G., Bindoff, L. A. <strong>Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase-gamma mutations.</strong> Neurology 64: 1204-1208, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15824347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15824347</a>] [<a href="https://doi.org/10.1212/01.WNL.0000156516.77696.5A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15824347">Winterthun et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15824347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Fadic, R., Russell, J. A., Vedanarayanan, V. V., Lehar, M., Kuncl, R. W., Johns, D. R. <strong>Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease.</strong> Neurology 49: 239-245, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9222196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9222196</a>] [<a href="https://doi.org/10.1212/wnl.49.1.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9222196">Fadic et al. (1997)</a> reported 4 unrelated patients with adult onset of severe sensory ataxic neuropathy in association with dysarthria and chronic progressive external ophthalmoplegia. Patients had ataxic gait, loss of distal proprioception and vibration, areflexia in the lower limbs, positive Romberg sign, and electrophysiologic and pathologic evidence of a peripheral axonal neuropathy. Other variable features included migraine and depression. Skeletal muscle biopsy showed myopathic changes with centralized nuclei and ragged-red fibers. Molecular analysis detected multiple mitochondrial DNA (mtDNA) deletions, ranging in size from 4.5 to 10 kb, in muscle and peripheral nerve. <a href="#2" class="mim-tip-reference" title="Fadic, R., Russell, J. A., Vedanarayanan, V. V., Lehar, M., Kuncl, R. W., Johns, D. R. <strong>Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease.</strong> Neurology 49: 239-245, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9222196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9222196</a>] [<a href="https://doi.org/10.1212/wnl.49.1.239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9222196">Fadic et al. (1997)</a> proposed the term 'SANDO.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9222196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Rantamaki, M., Krahe, R., Paetau, A., Cormand, B., Mononen, I., Udd, B. <strong>Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.</strong> Neurology 57: 1043-1049, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11571332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11571332</a>] [<a href="https://doi.org/10.1212/wnl.57.6.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11571332">Rantamaki et al. (2001)</a> reported a family in which 3 of 5 sibs were affected by progressive ataxia starting at age 30 years. Each patient showed gait and limb ataxia, dysarthria, dysphagia, nystagmus, hyporeflexia, decreased vibration and position sense, and mild cognitive impairment. One patient had epilepsy. MRI showed bilateral thalamic lesions and high-intensity signals in the cerebellar white matter. Measurements of sensory action potentials were consistent with a sensory axonal neuropathy and suggested a disorder of the central somatosensory pathways. Postmortem examination of 1 case revealed degenerative pathology and atrophic changes in the thalamus, brainstem, cerebellum, and spinal cord. The authors concluded that the disorder was most consistent with an autosomal recessive pattern of inheritance. Genetic analyses for mutations in the FXN gene (<a href="/entry/606829">606829</a>), several spinocerebellar ataxias, and mitochondrial diseases were negative, suggesting that this family exhibited a distinct hereditary spinocerebellar ataxia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11571332" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Van Goethem, G., Martin, J. J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C. <strong>Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.</strong> Neuromusc. Disord. 13: 133-142, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12565911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12565911</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00216-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12565911">Van Goethem et al. (2003)</a> reported a man with SANDO who had been rejected from compulsory military service at the age of 19 years because of a disturbance of balance, which progressed slowly during the third decade and became disabling with frequent falls. He presented at age 39 with moderately severe external ophthalmoparesis, mild dysarthria, and ataxic gait without other muscle weakness. The patient showed thalamic lesions on neuroimaging. The patient's parents, both 70 years of age, were clinically normal, as was his only brother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12565911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C. <strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong> Neurology 63: 1251-1257, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>] [<a href="https://doi.org/10.1212/01.wnl.0000140494.58732.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477547">Van Goethem et al. (2004)</a> reported 8 patients from 5 European families who presented with sensory ataxia without apparent muscle involvement; 1 of the families had been reported by <a href="#7" class="mim-tip-reference" title="Rantamaki, M., Krahe, R., Paetau, A., Cormand, B., Mononen, I., Udd, B. <strong>Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.</strong> Neurology 57: 1043-1049, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11571332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11571332</a>] [<a href="https://doi.org/10.1212/wnl.57.6.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11571332">Rantamaki et al. (2001)</a>. In a previously unreported family, a man had an 8-day episode of status epilepticus at age 18 years and an acute psychiatric illness with hyperventilation, gastrointestinal symptoms, and ataxia at age 23. At age 38, he demonstrated gait and limb ataxia, dysarthria, areflexia, distal loss of vibration and proprioception in the lower limbs, a sensory axonal peripheral neuropathy, and increased CSF protein. Other features included severe gastroparesis with progressive weight loss and dilated cardiomyopathy on echocardiogram. At age 38 years, he had an acute episode of stupor, hyperventilation, myoclonus, seizures, and lactic acidosis, and died at age 39 after numerous complications. Blepharoptosis and ophthalmoparesis were never noted. A muscle biopsy at age 34 years showed abnormal mitochondrial inclusions and some evidence of mtDNA deletions. The patient's sister had acute encephalopathy, myoclonus, partial seizures, cortical blindness, stupor, and sudden death at age 17 years. In a consanguineous Belgian family, a brother and sister reported progressive gait unsteadiness beginning in adolescence. By the fifth decade, both patients had ataxic gait, areflexia, distal sensory loss in the lower limbs, axonal neuropathy, and pes cavus. In addition, the sister had gaze-evoked nystagmus, dysarthria, was wheelchair-dependent, and had symmetric cerebellar white matter lesions on MRI. The brother had mild asymptomatic upward gaze paresis, cognitive decline, and cataracts. Two additional unrelated patients had an apparently sporadic disorder with ataxia, axonal neuropathy, dysarthria, and variable eye movement abnormalities. One patient had bilateral cerebellar white matter lesions on MRI. Muscle biopsies of the patients reported by <a href="#11" class="mim-tip-reference" title="Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C. <strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong> Neurology 63: 1251-1257, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>] [<a href="https://doi.org/10.1212/01.wnl.0000140494.58732.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477547">Van Goethem et al. (2004)</a> showed no signs of mitochondrial muscle disease, consistent with the lack of clinical abnormalities. However, some muscle biopsies showed low levels of mtDNA deletions. Extraocular ophthalmoparesis was not a main feature in these patients, only developing later in the disease and often in mild forms. The findings indicated significant phenotypic heterogeneity in patients with recessive mutations in the POLG gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11571332+15477547" 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="Mancuso, M., Filosto, M., Bellan, M., Liguori, R., Montagna, P., Baruzzi, A., DiMauro, S., Carelli, V. <strong>POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness.</strong> Neurology 62: 316-318, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14745080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14745080</a>] [<a href="https://doi.org/10.1212/wnl.62.2.316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14745080">Mancuso et al. (2004)</a> reported 2 Italian sibs, a male and a female, with an autosomal recessive neurologic disorder characterized by sensorimotor polyneuropathy, ataxia, and ophthalmoparesis. Onset was in the early twenties with gait disturbances, distal muscle weakness, paresthesias of the lower limbs, and decreased sensation. Bilateral ptosis and ophthalmoplegia were present in both sibs, and the brother also had progressive hearing loss and urinary and erectile dysfunction. Sural nerve biopsy showed loss of myelinated fibers and axonal degeneration without regeneration. Compound heterozygosity for 2 mutations in the POLG gene (<a href="/entry/174763#0009">174763.0009</a>; <a href="/entry/174763#0010">174763.0010</a>) were found in both patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14745080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Spinocerebellar Ataxia with Epilepsy</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., Engelsen, B. A., Moen, G., Bindoff, L. A. <strong>Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase-gamma mutations.</strong> Neurology 64: 1204-1208, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15824347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15824347</a>] [<a href="https://doi.org/10.1212/01.WNL.0000156516.77696.5A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15824347">Winterthun et al. (2005)</a> reported 4 unrelated families with a recessively inherited ataxia syndrome characterized by onset of headaches and/or seizures in childhood or adolescence (range 5 to 17 years). By their twenties, all patients developed cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus. Three patients developed status epilepticus, which was fatal in 1. Several patients showed MRI signal abnormalities deep in the cerebellum and in the thalamus. Muscle biopsies in most patients showed COX-negative fibers, and mtDNA deletions were found in all patients. Affected members from 2 families were homozygous for the same POLG mutation (A467T; <a href="/entry/174763#0002">174763.0002</a>), and patients from the remaining 2 families were compound heterozygous for 2 POLG mutations (<a href="/entry/174763#0013">174763.0013</a> and <a href="/entry/174763#0016">174763.0016</a>). <a href="#13" class="mim-tip-reference" title="Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., Engelsen, B. A., Moen, G., Bindoff, L. A. <strong>Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase-gamma mutations.</strong> Neurology 64: 1204-1208, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15824347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15824347</a>] [<a href="https://doi.org/10.1212/01.WNL.0000156516.77696.5A" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15824347">Winterthun et al. (2005)</a> emphasized that migraine, seizures, and myoclonus were especially frequent in this group of patients. <a href="#3" class="mim-tip-reference" title="Hakonen, A. H., Heiskanen, S., Juvonen, V., Lappalainen, I., Luoma, P. T., Rantamaki, M., Van Goethem, G., Lofgren, A., Hackman, P., Paetau, A., Kaakkola, S., Majamaa, K., Varilo, T., Udd, B., Kaariainen, H., Bindoff, L. A., Suomalainen, A. <strong>Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.</strong> Am. J. Hum. Genet. 77: 430-441, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16080118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16080118</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16080118[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/444548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16080118">Hakonen et al. (2005)</a> referred to this disorder as 'mitochondrial spinocerebellar ataxia-epilepsy syndrome' (MSCAE) or 'mitochondrial recessive ataxia syndrome' (MIRAS). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15824347+16080118" 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="Bird, T. D., Shaw, C. M. <strong>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong> J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/632821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">632821</a>] [<a href="https://doi.org/10.1136/jnnp.41.2.140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="632821">Bird and Shaw (1978)</a> reported a girl with juvenile-onset progressive myoclonic epilepsy. At age 15 years, she developed an awkward gait, clumsy hand coordination, deteriorating cognition, and nocturnal seizures associated with irregular EEG findings. The disorder was progressive, and she later developed nystagmus, dysarthria, ataxia, fine tremor, loss of distal vibratory sense and reflexes, and pes cavus. Late in the disorder, she developed severe myoclonic jerks and visual impairment, and became bedridden. She died of pneumonia at age 19 years. Neuropathologic examination showed brain atrophy and multifocal lesions in the cerebral cortex characterized by hypertrophic astrocytes, spongy degeneration, and neuronal loss. Fibrillar rod-like structures were seen in the hippocampus. There was widespread loss of Purkinje cells in the cerebellum, neuronal loss and gliosis in the brainstem, including the substantia nigra, and degeneration of the dorsal column of the spinal cord. Family history revealed a younger brother with a similar, but milder, disorder with onset at age 14. He had tremor, mild pes cavus, nystagmus, and peripheral neuropathy. At age 17, he did not have cognitive decline or myoclonic seizures, but he did have EEG abnormalities. <a href="#1" class="mim-tip-reference" title="Bird, T. D., Shaw, C. M. <strong>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong> J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/632821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">632821</a>] [<a href="https://doi.org/10.1136/jnnp.41.2.140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="632821">Bird and Shaw (1978)</a> noted some phenotypic similarities to the Ramsay-Hunt syndrome (<a href="/entry/213400">213400</a>) and dentatorubral degeneration (DRPLA; <a href="/entry/125370">125370</a>). In the 2 sibs with progressive myoclonic epilepsy originally reported by <a href="#1" class="mim-tip-reference" title="Bird, T. D., Shaw, C. M. <strong>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong> J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/632821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">632821</a>] [<a href="https://doi.org/10.1136/jnnp.41.2.140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="632821">Bird and Shaw (1978)</a>, <a href="#10" class="mim-tip-reference" title="Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others. <strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong> Am. J. Hum. Genet. 88: 138-149, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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.2010.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21276947">Tao et al. (2011)</a> identified 2 heterozygous variants on the same allele in the PRICKLE2 gene (R148H and V153I; <a href="/entry/608501#0001">608501.0001</a>). An unrelated patient with myoclonic seizures was heterozygous for a different PRICKLE2 variant (V605F; <a href="/entry/608501#0002">608501.0002</a>); no further details on this patient were provided. <a href="#10" class="mim-tip-reference" title="Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others. <strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong> Am. J. Hum. Genet. 88: 138-149, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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.2010.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21276947">Tao et al. (2011)</a> concluded that PRICKLE signaling is important in seizure prevention, and presented 2 hypotheses: (1) that PRICKLE affects cell polarity and contributes to the development of a functional neural network, and (2) that PRICKLE affects calcium signaling, which may play a role in seizure genesis if disrupted. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=632821+21276947" 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>By reevaluation of the sibs reported by <a href="#1" class="mim-tip-reference" title="Bird, T. D., Shaw, C. M. <strong>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong> J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/632821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">632821</a>] [<a href="https://doi.org/10.1136/jnnp.41.2.140" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="632821">Bird and Shaw (1978)</a>, who were classified as having progressive myoclonic epilepsy-5 (EPM5), <a href="#8" class="mim-tip-reference" title="Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M. <strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong> Am. J. Hum. Genet. 98: 588-589, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942291</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26942291">Sandford et al. (2016)</a> determined that the 2 heterozygous missense variants in the PRICKLE2 gene identified by <a href="#10" class="mim-tip-reference" title="Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others. <strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong> Am. J. Hum. Genet. 88: 138-149, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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.2010.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21276947">Tao et al. (2011)</a> occurred on opposite chromosomes, which would be more consistent with recessive inheritance. Furthermore, in these sibs, <a href="#8" class="mim-tip-reference" title="Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M. <strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong> Am. J. Hum. Genet. 98: 588-589, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942291</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26942291">Sandford et al. (2016)</a> identified compound heterozygous mutations in the POLG gene (A467T, <a href="/entry/174763#0002">174763.0002</a> on 1 allele, and W748S, <a href="/entry/174763#0013">174763.0013</a> and G497H, <a href="/entry/174763#0016">174763.0016</a> in cis on the other allele). <a href="#8" class="mim-tip-reference" title="Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M. <strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong> Am. J. Hum. Genet. 98: 588-589, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942291</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26942291">Sandford et al. (2016)</a> concluded that the phenotype resulted from the POLG mutations and not from the PRICKLE2 variants. <a href="#8" class="mim-tip-reference" title="Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M. <strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong> Am. J. Hum. Genet. 98: 588-589, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942291</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.01.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26942291">Sandford et al. (2016)</a> stated that the PRICKLE2 V605F variant reported in an unrelated patient by <a href="#10" class="mim-tip-reference" title="Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others. <strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong> Am. J. Hum. Genet. 88: 138-149, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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.2010.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21276947">Tao et al. (2011)</a> appears twice in the ExAC database, and thus is not consistent with its being pathogenic. In a response, <a href="#4" class="mim-tip-reference" title="Mahajan, V. B., Bassuk, A. G. <strong>Response to Sandford et al.: PRICKLE2 variants in epilepsy: a call for precision medicine</strong> Am. J. Hum. Genet. 98: 590-591, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942292</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.02.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26942292">Mahajan and Bassuk (2016)</a> maintained that the PRICKLE2 variants identified by <a href="#10" class="mim-tip-reference" title="Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others. <strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong> Am. J. Hum. Genet. 88: 138-149, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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.2010.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21276947">Tao et al. (2011)</a> contributed to the phenotype in their patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21276947+632821+26942292+26942291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of SANDO in the patients reported by <a href="#12" class="mim-tip-reference" title="Van Goethem, G., Martin, J. J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C. <strong>Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.</strong> Neuromusc. Disord. 13: 133-142, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12565911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12565911</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00216-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12565911">Van Goethem et al. (2003)</a> and <a href="#11" class="mim-tip-reference" title="Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C. <strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong> Neurology 63: 1251-1257, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>] [<a href="https://doi.org/10.1212/01.wnl.0000140494.58732.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477547">Van Goethem et al. (2004)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15477547+12565911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with SANDO, <a href="#12" class="mim-tip-reference" title="Van Goethem, G., Martin, J. J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C. <strong>Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.</strong> Neuromusc. Disord. 13: 133-142, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12565911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12565911</a>] [<a href="https://doi.org/10.1016/s0960-8966(02)00216-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12565911">Van Goethem et al. (2003)</a> identified compound heterozygosity for 2 mutations in the POLG gene (<a href="/entry/174763#0002">174763.0002</a>; <a href="/entry/174763#0005">174763.0005</a>). The finding indicated that SANDO is a variant of autosomal recessive PEO. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12565911" 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 3 Finnish sibs with SANDO reported by <a href="#7" class="mim-tip-reference" title="Rantamaki, M., Krahe, R., Paetau, A., Cormand, B., Mononen, I., Udd, B. <strong>Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.</strong> Neurology 57: 1043-1049, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11571332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11571332</a>] [<a href="https://doi.org/10.1212/wnl.57.6.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11571332">Rantamaki et al. (2001)</a>, <a href="#11" class="mim-tip-reference" title="Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C. <strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong> Neurology 63: 1251-1257, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>] [<a href="https://doi.org/10.1212/01.wnl.0000140494.58732.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477547">Van Goethem et al. (2004)</a> identified a homozygous mutation in the POLG gene (W748S; <a href="/entry/174763#0013">174763.0013</a>). Another unrelated Finnish patient had the same homozygous mutation. In 3 affected Belgian patients, 2 of whom were sibs, <a href="#11" class="mim-tip-reference" title="Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C. <strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong> Neurology 63: 1251-1257, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>] [<a href="https://doi.org/10.1212/01.wnl.0000140494.58732.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15477547">Van Goethem et al. (2004)</a> identified a homozygous mutation in the POLG gene (A467T; <a href="/entry/174763#0002">174763.0002</a>). A British patient with sporadic SANDO was compound heterozygous for the W748S and A467T mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11571332+15477547" 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="Schulte, C., Synofzik, M., Gasser, T., Schols, L. <strong>Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG mutations.</strong> Neurology 73: 898-900, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19752458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19752458</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b78488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19752458">Schulte et al. (2009)</a> identified homozygous or compound heterozygous POLG mutations in 9 of 26 patients from 23 families with cerebellar ataxia plus external ophthalmoplegia and/or sensory neuropathy. Two additional patients from this cohort had heterozygous POLG mutations, consistent with PEOA1. Noting that the molecular diagnosis of cerebellar ataxia can be difficult, <a href="#9" class="mim-tip-reference" title="Schulte, C., Synofzik, M., Gasser, T., Schols, L. <strong>Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG mutations.</strong> Neurology 73: 898-900, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19752458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19752458</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181b78488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19752458">Schulte et al. (2009)</a> found that for POLG-associated ataxia, the additional presence of ophthalmoplegia had a predictive value of 80%, whereas the presence of neuropathy had a predictive value of 45%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19752458" 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>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong>
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J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/632821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">632821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=632821" 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/10.1136/jnnp.41.2.140" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Fadic1997" class="mim-anchor"></a>
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Fadic, R., Russell, J. A., Vedanarayanan, V. V., Lehar, M., Kuncl, R. W., Johns, D. R.
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<strong>Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease.</strong>
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Neurology 49: 239-245, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9222196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9222196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9222196" 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/10.1212/wnl.49.1.239" target="_blank">Full Text</a>]
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<a id="Hakonen2005" class="mim-anchor"></a>
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Hakonen, A. H., Heiskanen, S., Juvonen, V., Lappalainen, I., Luoma, P. T., Rantamaki, M., Van Goethem, G., Lofgren, A., Hackman, P., Paetau, A., Kaakkola, S., Majamaa, K., Varilo, T., Udd, B., Kaariainen, H., Bindoff, L. A., Suomalainen, A.
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<strong>Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.</strong>
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Am. J. Hum. Genet. 77: 430-441, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16080118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16080118</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16080118[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=16080118" 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/10.1086/444548" target="_blank">Full Text</a>]
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<a id="Mahajan2016" class="mim-anchor"></a>
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Mahajan, V. B., Bassuk, A. G.
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<strong>Response to Sandford et al.: PRICKLE2 variants in epilepsy: a call for precision medicine</strong>
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Am. J. Hum. Genet. 98: 590-591, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942292</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26942292" 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.2016.02.002" target="_blank">Full Text</a>]
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<a id="Mancuso2004" class="mim-anchor"></a>
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Mancuso, M., Filosto, M., Bellan, M., Liguori, R., Montagna, P., Baruzzi, A., DiMauro, S., Carelli, V.
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<strong>POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness.</strong>
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Neurology 62: 316-318, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14745080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14745080</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14745080" 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/10.1212/wnl.62.2.316" target="_blank">Full Text</a>]
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<a id="Milone2010" class="mim-anchor"></a>
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Milone, M., Massie, R.
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<strong>Polymerase gamma 1 mutations: clinical correlations.</strong>
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Neurologist 16: 84-91, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220442</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20220442" 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/10.1097/NRL.0b013e3181c78a89" target="_blank">Full Text</a>]
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<a id="Rantamaki2001" class="mim-anchor"></a>
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Rantamaki, M., Krahe, R., Paetau, A., Cormand, B., Mononen, I., Udd, B.
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<strong>Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.</strong>
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Neurology 57: 1043-1049, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11571332/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11571332</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11571332" 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/10.1212/wnl.57.6.1043" target="_blank">Full Text</a>]
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<a id="Sandford2016" class="mim-anchor"></a>
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Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M.
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<strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong>
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Am. J. Hum. Genet. 98: 588-589, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26942291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26942291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26942291" 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.2016.01.009" target="_blank">Full Text</a>]
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<a id="Schulte2009" class="mim-anchor"></a>
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Schulte, C., Synofzik, M., Gasser, T., Schols, L.
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<strong>Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG mutations.</strong>
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Neurology 73: 898-900, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19752458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19752458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19752458" 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/10.1212/WNL.0b013e3181b78488" target="_blank">Full Text</a>]
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<a id="Tao2011" class="mim-anchor"></a>
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Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others.
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<strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong>
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Am. J. Hum. Genet. 88: 138-149, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21276947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21276947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21276947[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=21276947" 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.2010.12.012" target="_blank">Full Text</a>]
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<a id="Van Goethem2004" class="mim-anchor"></a>
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Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C.
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<strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong>
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Neurology 63: 1251-1257, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15477547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15477547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15477547" 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/10.1212/01.wnl.0000140494.58732.83" target="_blank">Full Text</a>]
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Van Goethem, G., Martin, J. J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C.
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<strong>Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.</strong>
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Neuromusc. Disord. 13: 133-142, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12565911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12565911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12565911" 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/s0960-8966(02)00216-x" target="_blank">Full Text</a>]
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<a id="Winterthun2005" class="mim-anchor"></a>
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Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., Engelsen, B. A., Moen, G., Bindoff, L. A.
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<strong>Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase-gamma mutations.</strong>
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Neurology 64: 1204-1208, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15824347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15824347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15824347" 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/10.1212/01.WNL.0000156516.77696.5A" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 3/23/2016
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Cassandra L. Kniffin - updated : 4/14/2011<br>Cassandra L. Kniffin - updated : 12/10/2010<br>Cassandra L. Kniffin - updated : 8/31/2005<br>Cassandra L. Kniffin - updated : 5/24/2005<br>Cassandra L. Kniffin - reorganized : 3/30/2005<br>Cassandra L. Kniffin - updated : 3/30/2005<br>Cassandra L. Kniffin - updated : 2/21/2005
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Cassandra L. Kniffin : 1/3/2003
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carol : 01/30/2024
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alopez : 03/17/2023<br>carol : 01/07/2022<br>carol : 08/16/2019<br>carol : 03/28/2016<br>carol : 3/25/2016<br>carol : 3/24/2016<br>ckniffin : 3/23/2016<br>wwang : 4/25/2011<br>ckniffin : 4/14/2011<br>terry : 1/25/2011<br>carol : 12/15/2010<br>ckniffin : 12/10/2010<br>alopez : 4/30/2010<br>ckniffin : 3/18/2010<br>alopez : 1/6/2010<br>wwang : 11/28/2006<br>wwang : 9/6/2005<br>ckniffin : 8/31/2005<br>wwang : 6/15/2005<br>wwang : 6/13/2005<br>ckniffin : 5/24/2005<br>carol : 3/30/2005<br>carol : 3/30/2005<br>terry : 3/30/2005<br>terry : 3/3/2005<br>ckniffin : 2/21/2005<br>carol : 1/7/2003<br>tkritzer : 1/7/2003<br>ckniffin : 1/6/2003
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<strong>#</strong> 607459
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SENSORY ATAXIC NEUROPATHY, DYSARTHRIA, AND OPHTHALMOPARESIS; SANDO
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<em>Alternative titles; symbols</em>
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SENSORY ATAXIC NEUROPATHY WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE
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Other entities represented in this entry:
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SPINOCEREBELLAR ATAXIA WITH EPILEPSY, INCLUDED; SCAE, INCLUDED
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EPILEPSY, PROGRESSIVE MYOCLONIC, WITH SENSORY ATAXIC NEUROPATHY, INCLUDED<br />
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EPILEPSY, PROGRESSIVE MYOCLONIC, 5, FORMERLY, INCLUDED; EPM5, FORMERLY, INCLUDED
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<strong>SNOMEDCT:</strong> 699328003, 717266001;
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<strong>ORPHA:</strong> 254881, 402082, 70595;
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<strong>DO:</strong> 0111276;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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15q26.1
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Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE)
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<span class="mim-font">
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607459
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Autosomal recessive
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<span class="mim-font">
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3
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POLG
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174763
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded DNA polymerase-gamma gene (POLG; 174763) on chromosome 15q26.</p><p>Recessive mutations in the POLG gene can also cause autosomal recessive progressive external ophthalmoplegia (PEOB; 258450), which shows overlapping features.</p>
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<strong>Description</strong>
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<p>SANDO is an autosomal recessive systemic disorder characterized mainly by adult onset of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) resulting from mitochondrial dysfunction and associated with mtDNA depletion in skeletal muscle and peripheral nerve tissue (Fadic et al., 1997). The phenotype varies widely, even within the same family, and can include myopathy, seizures, and hearing loss, but the common clinical feature appears to be sensory ataxia (review by Milone and Massie, 2010). </p><p>Spinocerebellar ataxia with epilepsy (SCAE) is a similar disorder with a higher frequency of migraine headaches and seizures (Winterthun et al., 2005). </p>
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<strong>Clinical Features</strong>
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<p>Fadic et al. (1997) reported 4 unrelated patients with adult onset of severe sensory ataxic neuropathy in association with dysarthria and chronic progressive external ophthalmoplegia. Patients had ataxic gait, loss of distal proprioception and vibration, areflexia in the lower limbs, positive Romberg sign, and electrophysiologic and pathologic evidence of a peripheral axonal neuropathy. Other variable features included migraine and depression. Skeletal muscle biopsy showed myopathic changes with centralized nuclei and ragged-red fibers. Molecular analysis detected multiple mitochondrial DNA (mtDNA) deletions, ranging in size from 4.5 to 10 kb, in muscle and peripheral nerve. Fadic et al. (1997) proposed the term 'SANDO.' </p><p>Rantamaki et al. (2001) reported a family in which 3 of 5 sibs were affected by progressive ataxia starting at age 30 years. Each patient showed gait and limb ataxia, dysarthria, dysphagia, nystagmus, hyporeflexia, decreased vibration and position sense, and mild cognitive impairment. One patient had epilepsy. MRI showed bilateral thalamic lesions and high-intensity signals in the cerebellar white matter. Measurements of sensory action potentials were consistent with a sensory axonal neuropathy and suggested a disorder of the central somatosensory pathways. Postmortem examination of 1 case revealed degenerative pathology and atrophic changes in the thalamus, brainstem, cerebellum, and spinal cord. The authors concluded that the disorder was most consistent with an autosomal recessive pattern of inheritance. Genetic analyses for mutations in the FXN gene (606829), several spinocerebellar ataxias, and mitochondrial diseases were negative, suggesting that this family exhibited a distinct hereditary spinocerebellar ataxia. </p><p>Van Goethem et al. (2003) reported a man with SANDO who had been rejected from compulsory military service at the age of 19 years because of a disturbance of balance, which progressed slowly during the third decade and became disabling with frequent falls. He presented at age 39 with moderately severe external ophthalmoparesis, mild dysarthria, and ataxic gait without other muscle weakness. The patient showed thalamic lesions on neuroimaging. The patient's parents, both 70 years of age, were clinically normal, as was his only brother. </p><p>Van Goethem et al. (2004) reported 8 patients from 5 European families who presented with sensory ataxia without apparent muscle involvement; 1 of the families had been reported by Rantamaki et al. (2001). In a previously unreported family, a man had an 8-day episode of status epilepticus at age 18 years and an acute psychiatric illness with hyperventilation, gastrointestinal symptoms, and ataxia at age 23. At age 38, he demonstrated gait and limb ataxia, dysarthria, areflexia, distal loss of vibration and proprioception in the lower limbs, a sensory axonal peripheral neuropathy, and increased CSF protein. Other features included severe gastroparesis with progressive weight loss and dilated cardiomyopathy on echocardiogram. At age 38 years, he had an acute episode of stupor, hyperventilation, myoclonus, seizures, and lactic acidosis, and died at age 39 after numerous complications. Blepharoptosis and ophthalmoparesis were never noted. A muscle biopsy at age 34 years showed abnormal mitochondrial inclusions and some evidence of mtDNA deletions. The patient's sister had acute encephalopathy, myoclonus, partial seizures, cortical blindness, stupor, and sudden death at age 17 years. In a consanguineous Belgian family, a brother and sister reported progressive gait unsteadiness beginning in adolescence. By the fifth decade, both patients had ataxic gait, areflexia, distal sensory loss in the lower limbs, axonal neuropathy, and pes cavus. In addition, the sister had gaze-evoked nystagmus, dysarthria, was wheelchair-dependent, and had symmetric cerebellar white matter lesions on MRI. The brother had mild asymptomatic upward gaze paresis, cognitive decline, and cataracts. Two additional unrelated patients had an apparently sporadic disorder with ataxia, axonal neuropathy, dysarthria, and variable eye movement abnormalities. One patient had bilateral cerebellar white matter lesions on MRI. Muscle biopsies of the patients reported by Van Goethem et al. (2004) showed no signs of mitochondrial muscle disease, consistent with the lack of clinical abnormalities. However, some muscle biopsies showed low levels of mtDNA deletions. Extraocular ophthalmoparesis was not a main feature in these patients, only developing later in the disease and often in mild forms. The findings indicated significant phenotypic heterogeneity in patients with recessive mutations in the POLG gene. </p><p>Mancuso et al. (2004) reported 2 Italian sibs, a male and a female, with an autosomal recessive neurologic disorder characterized by sensorimotor polyneuropathy, ataxia, and ophthalmoparesis. Onset was in the early twenties with gait disturbances, distal muscle weakness, paresthesias of the lower limbs, and decreased sensation. Bilateral ptosis and ophthalmoplegia were present in both sibs, and the brother also had progressive hearing loss and urinary and erectile dysfunction. Sural nerve biopsy showed loss of myelinated fibers and axonal degeneration without regeneration. Compound heterozygosity for 2 mutations in the POLG gene (174763.0009; 174763.0010) were found in both patients. </p><p><strong><em>Spinocerebellar Ataxia with Epilepsy</em></strong></p><p>
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Winterthun et al. (2005) reported 4 unrelated families with a recessively inherited ataxia syndrome characterized by onset of headaches and/or seizures in childhood or adolescence (range 5 to 17 years). By their twenties, all patients developed cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus. Three patients developed status epilepticus, which was fatal in 1. Several patients showed MRI signal abnormalities deep in the cerebellum and in the thalamus. Muscle biopsies in most patients showed COX-negative fibers, and mtDNA deletions were found in all patients. Affected members from 2 families were homozygous for the same POLG mutation (A467T; 174763.0002), and patients from the remaining 2 families were compound heterozygous for 2 POLG mutations (174763.0013 and 174763.0016). Winterthun et al. (2005) emphasized that migraine, seizures, and myoclonus were especially frequent in this group of patients. Hakonen et al. (2005) referred to this disorder as 'mitochondrial spinocerebellar ataxia-epilepsy syndrome' (MSCAE) or 'mitochondrial recessive ataxia syndrome' (MIRAS). </p><p>Bird and Shaw (1978) reported a girl with juvenile-onset progressive myoclonic epilepsy. At age 15 years, she developed an awkward gait, clumsy hand coordination, deteriorating cognition, and nocturnal seizures associated with irregular EEG findings. The disorder was progressive, and she later developed nystagmus, dysarthria, ataxia, fine tremor, loss of distal vibratory sense and reflexes, and pes cavus. Late in the disorder, she developed severe myoclonic jerks and visual impairment, and became bedridden. She died of pneumonia at age 19 years. Neuropathologic examination showed brain atrophy and multifocal lesions in the cerebral cortex characterized by hypertrophic astrocytes, spongy degeneration, and neuronal loss. Fibrillar rod-like structures were seen in the hippocampus. There was widespread loss of Purkinje cells in the cerebellum, neuronal loss and gliosis in the brainstem, including the substantia nigra, and degeneration of the dorsal column of the spinal cord. Family history revealed a younger brother with a similar, but milder, disorder with onset at age 14. He had tremor, mild pes cavus, nystagmus, and peripheral neuropathy. At age 17, he did not have cognitive decline or myoclonic seizures, but he did have EEG abnormalities. Bird and Shaw (1978) noted some phenotypic similarities to the Ramsay-Hunt syndrome (213400) and dentatorubral degeneration (DRPLA; 125370). In the 2 sibs with progressive myoclonic epilepsy originally reported by Bird and Shaw (1978), Tao et al. (2011) identified 2 heterozygous variants on the same allele in the PRICKLE2 gene (R148H and V153I; 608501.0001). An unrelated patient with myoclonic seizures was heterozygous for a different PRICKLE2 variant (V605F; 608501.0002); no further details on this patient were provided. Tao et al. (2011) concluded that PRICKLE signaling is important in seizure prevention, and presented 2 hypotheses: (1) that PRICKLE affects cell polarity and contributes to the development of a functional neural network, and (2) that PRICKLE affects calcium signaling, which may play a role in seizure genesis if disrupted. </p><p>By reevaluation of the sibs reported by Bird and Shaw (1978), who were classified as having progressive myoclonic epilepsy-5 (EPM5), Sandford et al. (2016) determined that the 2 heterozygous missense variants in the PRICKLE2 gene identified by Tao et al. (2011) occurred on opposite chromosomes, which would be more consistent with recessive inheritance. Furthermore, in these sibs, Sandford et al. (2016) identified compound heterozygous mutations in the POLG gene (A467T, 174763.0002 on 1 allele, and W748S, 174763.0013 and G497H, 174763.0016 in cis on the other allele). Sandford et al. (2016) concluded that the phenotype resulted from the POLG mutations and not from the PRICKLE2 variants. Sandford et al. (2016) stated that the PRICKLE2 V605F variant reported in an unrelated patient by Tao et al. (2011) appears twice in the ExAC database, and thus is not consistent with its being pathogenic. In a response, Mahajan and Bassuk (2016) maintained that the PRICKLE2 variants identified by Tao et al. (2011) contributed to the phenotype in their patients. </p>
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<strong>Inheritance</strong>
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</h4>
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<p>The transmission pattern of SANDO in the patients reported by Van Goethem et al. (2003) and Van Goethem et al. (2004) was consistent with autosomal recessive inheritance. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In a patient with SANDO, Van Goethem et al. (2003) identified compound heterozygosity for 2 mutations in the POLG gene (174763.0002; 174763.0005). The finding indicated that SANDO is a variant of autosomal recessive PEO. </p><p>In 3 Finnish sibs with SANDO reported by Rantamaki et al. (2001), Van Goethem et al. (2004) identified a homozygous mutation in the POLG gene (W748S; 174763.0013). Another unrelated Finnish patient had the same homozygous mutation. In 3 affected Belgian patients, 2 of whom were sibs, Van Goethem et al. (2004) identified a homozygous mutation in the POLG gene (A467T; 174763.0002). A British patient with sporadic SANDO was compound heterozygous for the W748S and A467T mutations. </p><p>Schulte et al. (2009) identified homozygous or compound heterozygous POLG mutations in 9 of 26 patients from 23 families with cerebellar ataxia plus external ophthalmoplegia and/or sensory neuropathy. Two additional patients from this cohort had heterozygous POLG mutations, consistent with PEOA1. Noting that the molecular diagnosis of cerebellar ataxia can be difficult, Schulte et al. (2009) found that for POLG-associated ataxia, the additional presence of ophthalmoplegia had a predictive value of 80%, whereas the presence of neuropathy had a predictive value of 45%. </p>
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p class="mim-text-font">
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Bird, T. D., Shaw, C. M.
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<strong>Progressive myoclonus and epilepsy with dentatorubral degeneration: a clinicopathological study of the Ramsay Hunt syndrome.</strong>
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J. Neurol. Neurosurg. Psychiat. 41: 140-149, 1978.
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[PubMed: 632821]
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[Full Text: https://doi.org/10.1136/jnnp.41.2.140]
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<p class="mim-text-font">
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Fadic, R., Russell, J. A., Vedanarayanan, V. V., Lehar, M., Kuncl, R. W., Johns, D. R.
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<strong>Sensory ataxic neuropathy as the presenting feature of a novel mitochondrial disease.</strong>
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Neurology 49: 239-245, 1997.
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[PubMed: 9222196]
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[Full Text: https://doi.org/10.1212/wnl.49.1.239]
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</li>
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<li>
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<p class="mim-text-font">
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Hakonen, A. H., Heiskanen, S., Juvonen, V., Lappalainen, I., Luoma, P. T., Rantamaki, M., Van Goethem, G., Lofgren, A., Hackman, P., Paetau, A., Kaakkola, S., Majamaa, K., Varilo, T., Udd, B., Kaariainen, H., Bindoff, L. A., Suomalainen, A.
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<strong>Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin.</strong>
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Am. J. Hum. Genet. 77: 430-441, 2005.
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[PubMed: 16080118]
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[Full Text: https://doi.org/10.1086/444548]
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<li>
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<p class="mim-text-font">
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Mahajan, V. B., Bassuk, A. G.
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<strong>Response to Sandford et al.: PRICKLE2 variants in epilepsy: a call for precision medicine</strong>
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Am. J. Hum. Genet. 98: 590-591, 2016.
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[PubMed: 26942292]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.02.002]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mancuso, M., Filosto, M., Bellan, M., Liguori, R., Montagna, P., Baruzzi, A., DiMauro, S., Carelli, V.
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<strong>POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness.</strong>
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Neurology 62: 316-318, 2004.
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[PubMed: 14745080]
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[Full Text: https://doi.org/10.1212/wnl.62.2.316]
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<li>
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<p class="mim-text-font">
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Milone, M., Massie, R.
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<strong>Polymerase gamma 1 mutations: clinical correlations.</strong>
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Neurologist 16: 84-91, 2010.
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[PubMed: 20220442]
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[Full Text: https://doi.org/10.1097/NRL.0b013e3181c78a89]
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</li>
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<li>
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<p class="mim-text-font">
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Rantamaki, M., Krahe, R., Paetau, A., Cormand, B., Mononen, I., Udd, B.
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<strong>Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.</strong>
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Neurology 57: 1043-1049, 2001.
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[PubMed: 11571332]
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[Full Text: https://doi.org/10.1212/wnl.57.6.1043]
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<li>
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<p class="mim-text-font">
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Sandford, E., Bird, T. D., Li, J. Z., Burmeister, M.
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<strong>PRICKLE2 mutations might not be involved in epilepsy. (Letter)</strong>
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Am. J. Hum. Genet. 98: 588-589, 2016.
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[PubMed: 26942291]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.01.009]
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Schulte, C., Synofzik, M., Gasser, T., Schols, L.
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<strong>Ataxia with ophthalmoplegia or sensory neuropathy is frequently caused by POLG mutations.</strong>
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Neurology 73: 898-900, 2009.
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[PubMed: 19752458]
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[Full Text: https://doi.org/10.1212/WNL.0b013e3181b78488]
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Tao, H., Manak, J. R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N. S., Yang, T., Wu, S., Chen, S., Fox, M. H., Gurnett, C., and 24 others.
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<strong>Mutations in prickle orthologs cause seizures in flies, mice, and humans.</strong>
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Am. J. Hum. Genet. 88: 138-149, 2011.
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[PubMed: 21276947]
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[Full Text: https://doi.org/10.1016/j.ajhg.2010.12.012]
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</p>
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<li>
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Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J. J., De Jonghe, P., Suomalainen, A., Udd, B., Van Broeckhoven, C.
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<strong>POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.</strong>
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Neurology 63: 1251-1257, 2004.
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[PubMed: 15477547]
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[Full Text: https://doi.org/10.1212/01.wnl.0000140494.58732.83]
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</p>
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</li>
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Van Goethem, G., Martin, J. J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M., Ceuterick, C., De Jonghe, P., Van Broeckhoven, C.
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<strong>Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia.</strong>
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Neuromusc. Disord. 13: 133-142, 2003.
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[PubMed: 12565911]
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[Full Text: https://doi.org/10.1016/s0960-8966(02)00216-x]
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</p>
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Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., Engelsen, B. A., Moen, G., Bindoff, L. A.
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<strong>Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase-gamma mutations.</strong>
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Neurology 64: 1204-1208, 2005.
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[PubMed: 15824347]
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[Full Text: https://doi.org/10.1212/01.WNL.0000156516.77696.5A]
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Cassandra L. Kniffin - updated : 3/23/2016<br>Cassandra L. Kniffin - updated : 4/14/2011<br>Cassandra L. Kniffin - updated : 12/10/2010<br>Cassandra L. Kniffin - updated : 8/31/2005<br>Cassandra L. Kniffin - updated : 5/24/2005<br>Cassandra L. Kniffin - reorganized : 3/30/2005<br>Cassandra L. Kniffin - updated : 3/30/2005<br>Cassandra L. Kniffin - updated : 2/21/2005
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Cassandra L. Kniffin : 1/3/2003
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