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<title>
Entry
- #607694 - LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD7
- OMIM
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<span class="h4">#607694</span>
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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/607694"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS312080"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM" 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>
<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;">&#9658;</span>EuroGentest</div>
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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=16698&Typ=Pat" title="Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hypomyelinating leukodystr…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=23550&Typ=Pat" title="Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hypomyelination-cerebellar…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=23551&Typ=Pat" title="Tremor-ataxia-central hypomyelination syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Tremor-ataxia-central hypo…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11107&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Odontoleukodystrophy&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11816&Typ=Pat" title="Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hypomyelination-hypogonado…&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK99167/" 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>
<div><a href="https://www.diseaseinfosearch.org/x/4200" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607694[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>
<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;">&#9658;</span>Orphanet</div>
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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=137639" title="Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hypomyelinating leukodystr…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=447893" title="Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hypomyelination-cerebellar…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=447896" title="Tremor-ataxia-central hypomyelination syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Tremor-ataxia-central hypo…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Odontoleukodystrophy</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=88637" title="Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hypomyelination-hypogonado…</a></div>
</div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/87cc0deb-a3d6-45fa-a742-0e0586bb8cfb/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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</a>
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</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0060794" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/607694" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0060794" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
</div>
</div>
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</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 721846006<br />
<strong>ICD10CM:</strong> G11.5<br />
<strong>ORPHA:</strong> 137639, 447893, 447896, 77295, 88637<br />
<strong>DO:</strong> 0060794<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
607694
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD7
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
LEUKOENCEPHALOPATHY, HYPOMYELINATING, WITH ATAXIA AND DELAYED DENTITION<br />
ATAXIA, DELAYED DENTITION, AND HYPOMYELINATION; ADDH<br />
LEUKODYSTROPHY, HYPOMYELINATING, WITH HYPODONTIA AND HYPOGONADOTROPIC HYPOGONADISM<br />
4H SYNDROME<br />
4H LEUKODYSTROPHY 1
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/327?start=-3&limit=10&highlight=327">
10q22.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607694"> 607694 </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">
POLR3A
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614258"> 614258 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
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<a href="/clinicalSynopsis/607694" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
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<a href="/phenotypicSeries/PS312080" class="btn btn-info" role="button"> Phenotypic Series </a>
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/607694" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/607694" 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> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Abnormal smooth pursuit <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836393</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000617" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000617</a>]</span><br /> -
Vertical gaze limitation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277006&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277006</a>]</span><br /> -
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 /> -
Myopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57190000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57190000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027092&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027092</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span><br /> -
Optic atrophy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Drooling (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62718007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62718007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0003781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003781</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed dentition <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5639000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5639000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239174&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239174</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span><br /> -
Delayed eruption of the upper median incisors <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230366&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230366</a>]</span><br /> -
Hypodontia (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64969001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64969001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>]</span><br /> -
Oligodontia (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/787414001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">787414001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64969001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64969001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4082304&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4082304</a>, <a href="https://bioportal.bioontology.org/search?q=C0020608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020608</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000668" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000668</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000677</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000677" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000677</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Dysphagia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Bladder </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Bladder dysfunction (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40492006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40492006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232841&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232841</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<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">
- Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
Cerebellar ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
Motor regression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276997&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276997</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033044</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033044</a>]</span><br /> -
Upper motor neuron signs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0749870&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0749870</a>]</span><br /> -
Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
Postural tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56610005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56610005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234378</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002174" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002174</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002174" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002174</a>]</span><br /> -
Cerebellar signs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0742038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0742038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001317</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001317</a>]</span><br /> -
Dysmetria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32566006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32566006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234162&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234162</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001310" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001310</a>]</span><br /> -
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 /> -
Seizures, partial complex (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002384" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002384</a>]</span><br /> -
Developmental delay (in about half of patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Cognitive regression, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277000&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034332</a>]</span><br /> -
Leukodystrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/192781003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">192781003</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/330.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">330.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023520&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023520</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002415" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002415</a>]</span><br /> -
Hypomyelination <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111007000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111007000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0544820&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0544820</a>]</span><br /> -
Thinning of the corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5441562&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441562</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033725</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033725</a>]</span><br /> -
Cortical atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551583</a>, <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002120" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002120</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002120" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002120</a>]</span><br /> -
Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br /> -
White matter rarefaction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4230367&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4230367</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Peripheral Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Peripheral neuropathy (some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42658009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42658009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302226006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302226006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G64" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G64</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/350-359.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">350-359.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4721453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4721453</a>, <a href="https://bioportal.bioontology.org/search?q=C0031117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0031117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000759</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001271" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001271</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>]</span><br /> -
Decreased vibratory and positional sense (some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277002</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Delayed puberty (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/400003000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">400003000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/123526007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">123526007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E30.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E30.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034012&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034012</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000823" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000823</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000823" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000823</a>]</span><br /> -
Hypogonadotropic hypogonadism (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22053006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22053006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33927004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405769009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405769009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E23.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E23.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q98.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q98.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/758.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">758.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271623</a>, <a href="https://bioportal.bioontology.org/search?q=C0022735&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022735</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000044" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000044</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in childhood (range 1 to 12 years)<br /> -
Variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</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 /> -
Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
Many patients become wheelchair-bound by second or third decade<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the RNA polymerase III, subunit A gene (POLR3A, <a href="/entry/614258#0001">614258.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Leukodystrophy, hypomyelinating
- <a href="/phenotypicSeries/PS312080">PS312080</a>
- 28 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/539?start=-3&limit=10&highlight=539"> 1p34.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619688"> Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619688"> 619688 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616136"> RNF220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616136"> 616136 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1715?start=-3&limit=10&highlight=1715"> 1q41 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617951"> Leukodystrophy, hypomyelinating, 15 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617951"> 617951 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138295"> EPRS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/138295"> 138295 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1743?start=-3&limit=10&highlight=1743"> 1q42.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618404"> Leukodystrophy, hypomyelinating, 18 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618404"> 618404 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615843"> DEGS1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615843"> 615843 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1752?start=-3&limit=10&highlight=1752"> 1q42.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618688"> Leukodystrophy, hypomyelinating, 19, transient infantile </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618688"> 618688 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618685"> TMEM63A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618685"> 618685 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1754?start=-3&limit=10&highlight=1754"> 1q42.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616420"> Leukodystrophy, hypomyelinating, 10 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616420"> 616420 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616406"> PYCR2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616406"> 616406 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1773?start=-3&limit=10&highlight=1773"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608804"> Leukodystrophy, hypomyelinating, 2 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608804"> 608804 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608803"> GJC2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608803"> 608803 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/436?start=-3&limit=10&highlight=436"> 2p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620675"> Leukodystrophy, hypomyelinating, 27 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620675"> 620675 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616404"> POLR1A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616404"> 616404 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/464?start=-3&limit=10&highlight=464"> 2q11.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620978"> ?Leukodystrophy, hypomyelinating, 28 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620978"> 620978 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188860"> MAL </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188860"> 188860 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/654?start=-3&limit=10&highlight=654"> 2q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620243"> Leukodystrophy, hypomyelinating, 25 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620243"> 620243 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618978"> TMEM163 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618978"> 618978 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/891?start=-3&limit=10&highlight=891"> 2q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612233"> Leukodystrophy, hypomyelinating, 4 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612233"> 612233 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/118190"> HSPD1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/118190"> 118190 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/859?start=-3&limit=10&highlight=859"> 3q26.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619328"> Leukodystrophy, hypomyelinating, 22 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619328"> 619328 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601326"> CLDN11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601326"> 601326 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/465?start=-3&limit=10&highlight=465"> 4q24 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/260600"> Leukodystrophy, hypomyelinating, 3 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/260600"> 260600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603605"> AIMP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603605"> 603605 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/743?start=-3&limit=10&highlight=743"> 5q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616140"> Leukodystrophy, hypomyelinating, 9 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616140"> 616140 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/107820"> RARS1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/107820"> 107820 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/528?start=-3&limit=10&highlight=528"> 6p21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616494"> Leukodystrophy, hypomyelinating, 11 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616494"> 616494 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610060"> POLR1C </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610060"> 610060 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/542?start=-3&limit=10&highlight=542"> 6p21.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620269"> Leukodystrophy, hypomyelinating, 26, with chondrodysplasia </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620269"> 620269 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610788"> SLC35B2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610788"> 610788 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/52?start=-3&limit=10&highlight=52"> 7p22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618006"> Leukodystrophy, hypomyelinating, 17 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618006"> 618006 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600859"> AIMP2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600859"> 600859 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/74?start=-3&limit=10&highlight=74"> 7p21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617964"> Leukodystrophy, hypomyelinating, 16 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617964"> 617964 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613413"> TMEM106B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613413"> 613413 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/110?start=-3&limit=10&highlight=110"> 7p15.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610532"> Leukodystrophy, hypomyelinating, 5 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610532"> 610532 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610531"> HYCC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610531"> 610531 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/327?start=-3&limit=10&highlight=327"> 10q22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607694"> Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607694"> 607694 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614258"> POLR3A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614258"> 614258 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/808?start=-3&limit=10&highlight=808"> 11q14.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616881"> Leukodystrophy, hypomyelinating, 13 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616881"> 616881 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614908"> HIKESHI </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614908"> 614908 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/1003?start=-3&limit=10&highlight=1003"> 11q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616683"> Leukodystrophy, hypomyelinating, 12 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616683"> 616683 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608549"> VPS11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608549"> 608549 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/757?start=-3&limit=10&highlight=757"> 12q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614381"> Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614381"> 614381 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614366"> POLR3B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614366"> 614366 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/13/106?start=-3&limit=10&highlight=106"> 13q13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617899"> Leukodystrophy, hypomyelinating, 14 </a>
</span>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
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<span class="mim-font">
<a href="/entry/617899"> 617899 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/610553"> UFM1 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/610553"> 610553 </a>
</span>
</td>
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<span class="mim-font">
<a href="/geneMap/13/319?start=-3&limit=10&highlight=319"> 13q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619851"> ?Leukodystrophy, hypomyelinating, 24 </a>
</span>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
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<span class="mim-font">
<a href="/entry/619851"> 619851 </a>
</span>
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<span class="mim-font">
<a href="/entry/605868"> ATP11A </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/605868"> 605868 </a>
</span>
</td>
</tr>
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<span class="mim-font">
<a href="/geneMap/16/11?start=-3&limit=10&highlight=11"> 16p13.3 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/619310"> Leukodystrophy, hypomyelinating, 21 </a>
</span>
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<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>
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<span class="mim-font">
<a href="/entry/619310"> 619310 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/606007"> POLR3K </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/606007"> 606007 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/563?start=-3&limit=10&highlight=563"> 17q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619071"> ?Leukodystrophy, hypomyelinating, 20 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619071"> 619071 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/123830"> CNP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123830"> 123830 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/185?start=-3&limit=10&highlight=185"> 19p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612438"> Leukodystrophy, hypomyelinating, 6 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612438"> 612438 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602662"> TUBB4A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602662"> 602662 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/532?start=-3&limit=10&highlight=532"> Xq22.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/312080"> Pelizaeus-Merzbacher disease </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/312080"> 312080 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300401"> PLP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300401"> 300401 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-7 (HLD7) is caused by homozygous or compound heterozygous mutation in the POLR3A gene (<a href="/entry/614258">614258</a>) on chromosome 10q22.</p>
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability (summary by <a href="#2" class="mim-tip-reference" title="Bernard, G., Chouery, E., Putorti, M. L., Tetreault, M., Takanohashi, A., Carosso, G., Clement, I., Boespflug-Tanguy, O., Rodriguez, D., Delague, V., Abou Ghoch, J., Jalkh, N., Dorboz, I., Fribourg, S., Teichmann, M., Megarbane, A., Schiffmann, R., Vanderver, A., Brais, B. &lt;strong&gt;Mutations of POLR3A encoding a catalytic subunit of RNA polymerase pol III cause a recessive hypomyelinating leukodystrophy.&lt;/strong&gt; Am. J. Hum. Genet. 89: 415-423, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 972 only, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21855841/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21855841&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21855841[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2011.07.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21855841">Bernard et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21855841" 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>See also HLD8 (<a href="/entry/614381">614381</a>), which has similar features and is caused by mutation in the POLR3B gene (<a href="/entry/614366">614366</a>) on chromosome 12q23. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see <a href="/entry/312080">312080</a>.</p>
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<strong>Clinical Features</strong>
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</h4>
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<p>In an inbred Syrian pedigree, <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a> described oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome. Age at onset was about 12 years. Abnormalities in the white matter and cortical atrophy were demonstrated by magnetic resonance imaging. In 1 sibship of 8, 3 girls and a boy were affected; the parents were consanguineous. <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a> suggested that this might represent a distinct form of dentoleukoencephalopathy with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12605447" 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="Wolf, N. I., Harting, I., Boltshauser, E., Wiegand, G., Koch, M. J., Schmitt-Mechelke, T., Martin, E., Zschocke, J., Uhlenberg, B., Hoffmann, G. F., Weber, L., Ebinger, F., Rating, D. &lt;strong&gt;Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.&lt;/strong&gt; Neurology 64: 1461-1464, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15851747/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15851747&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000158615.56071.E3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15851747">Wolf et al. (2005)</a> reported 4 unrelated German or Swiss girls with early onset of progressive ataxia during the second year of life, mild to moderate brain hypomyelination, cerebellar atrophy, and delayed dentition. The first teeth to appear were the deciduous molars. Some patients were missing permanent teeth. All patients also had short stature. <a href="#7" class="mim-tip-reference" title="Wolf, N. I., Harting, I., Boltshauser, E., Wiegand, G., Koch, M. J., Schmitt-Mechelke, T., Martin, E., Zschocke, J., Uhlenberg, B., Hoffmann, G. F., Weber, L., Ebinger, F., Rating, D. &lt;strong&gt;Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.&lt;/strong&gt; Neurology 64: 1461-1464, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15851747/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15851747&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000158615.56071.E3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15851747">Wolf et al. (2005)</a> considered the disorder clinically distinct from that reported by <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a> because in the Syrian pedigree the MRI did not show hypomyelination, but demyelination mainly of the pyramidal tracts and of the subcortical matter, the onset of ataxia occurred after the age of 10 years, and the pattern of tooth agenesis was different. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15851747+12605447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Wolf, N. I., Harting, I., Innes, A. M., Parzer, S., Zeitler, P., Schneider, A., Wolff, A., Baier, K., Zschocke, J., Ebinger, F., Boltshauser, E., Rating, D. &lt;strong&gt;Ataxia, delayed dentition and hypomyelination: a novel leukoencephalopathy.&lt;/strong&gt; Neuropediatrics 38: 64-70, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17712733/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17712733&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1055/s-2007-985137&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17712733">Wolf et al. (2007)</a> reported 4 additional patients, including 3 boys, with ataxia, delayed dentition, and hypomyelination similar to their earlier report. All had delayed motor development with early-onset ataxia, tremor, dysarthria, and hypometric saccades. Pyramidal signs were variable, and most had mild cognitive dysfunction. Two patients had neonatal teeth, and all showed delayed dentition and abnormal order of tooth eruption. MRI showed hypomyelination of the supratentorial white matter, with thin corpus callosum and cerebellar atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17712733" 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="Saitsu, H., Osaka, H., Sasaki, M., Takanashi, J., Hamada, K., Yamashita, A., Shibayama, H., Shiina, M., Kondo, Y., Nishiyama, K., Tsurusaki, Y., Miyake, N., Doi, H., Ogata, K., Inoue, K., Matsumoto, N. &lt;strong&gt;Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy.&lt;/strong&gt; Am. J. Hum. Genet. 89: 644-651, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22036171/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22036171&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22036171[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2011.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22036171">Saitsu et al. (2011)</a> reported a 17-year-old Japanese boy with HLD7 confirmed by genetic analysis (<a href="/entry/614258#0006">614258.0006</a> and <a href="/entry/614258#0007">614258.0007</a>). He showed normal development until age 4, when mild tremors were noted. He later developed cerebellar signs, including expressive ataxic speech, intention tremor, poor finger-to-nose test, dysdiadochokinesis, dysmetria, and wide-based ataxic gait. He also showed intellectual disability with an IQ of 57. Other features included severe myopia and unilateral sensorineural deafness. The motor deterioration was progressive, and he became wheelchair-bound around age 14 years. Brain MRI showed a hypoplastic corpus callosum, cerebellar atrophy, and white matter lesions in the basal ganglia. He did not have hypodontia or hypogonadism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22036171" 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>Clinical Variability</em></strong></p><p>
<a href="#6" class="mim-tip-reference" title="Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K. &lt;strong&gt;Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.&lt;/strong&gt; Neurology 67: 2066-2069, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17159124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17159124&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17159124[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000247666.28904.35&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17159124">Timmons et al. (2006)</a> reported 4 unrelated patients with delayed tooth eruption and hypodontia of permanent teeth. Three patients were otherwise normal until age 12 years, when progressive hypomyelination and dysmyelination resulted in ataxia, dysmetria, spasticity, dysarthria, and extensor plantar responses. The fourth patient had onset at age 7. None of the patients had spontaneous puberty due to hypogonadotropic hypogonadism. There were also cognitive deficits. Sural nerve biopsy showed granular debris-lined clefts, expanded abaxonal space, vacuolar disruption, and loss of normal myelin periodicity. Brain MRI showed central hypomyelination and cerebellar atrophy. <a href="#6" class="mim-tip-reference" title="Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K. &lt;strong&gt;Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.&lt;/strong&gt; Neurology 67: 2066-2069, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17159124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17159124&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17159124[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000247666.28904.35&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17159124">Timmons et al. (2006)</a> proposed the designation '4H syndrome.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17159124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B. &lt;strong&gt;Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.&lt;/strong&gt; Neurogenetics 11: 457-464, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20640464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20640464&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0251-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20640464">Bernard et al. (2010)</a> reported 6 living patients and 1 deceased patient from 5 French Canadian families with a similar form of very early childhood-onset hypomyelinating leukodystrophy. Two of the families were consanguineous. The average age at onset was 2.5 years (range 1 to 5) and all presented with motor regression, ataxia, tremor, and spasticity. Other features included dysarthria, hyperreflexia, extensor plantar responses, abnormal bladder function, abnormal saccades, and nystagmus. Most became wheelchair-bound by later childhood. Less common features included dysphagia, drooling, optic atrophy, and complex partial seizures. Cognitive decline was mild, but noticeable. Two of 7 patients had some degree of hypodontia, and 1 had hypogonadotropic hypogonadism. <a href="#3" class="mim-tip-reference" title="Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B. &lt;strong&gt;Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.&lt;/strong&gt; Neurogenetics 11: 457-464, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20640464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20640464&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0251-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20640464">Bernard et al. (2010)</a> recognized the phenotypic overlap with the patients reported by <a href="#7" class="mim-tip-reference" title="Wolf, N. I., Harting, I., Boltshauser, E., Wiegand, G., Koch, M. J., Schmitt-Mechelke, T., Martin, E., Zschocke, J., Uhlenberg, B., Hoffmann, G. F., Weber, L., Ebinger, F., Rating, D. &lt;strong&gt;Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.&lt;/strong&gt; Neurology 64: 1461-1464, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15851747/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15851747&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.WNL.0000158615.56071.E3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15851747">Wolf et al. (2005)</a> and <a href="#6" class="mim-tip-reference" title="Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K. &lt;strong&gt;Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.&lt;/strong&gt; Neurology 67: 2066-2069, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17159124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17159124&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17159124[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000247666.28904.35&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17159124">Timmons et al. (2006)</a>, but noted that not all the French Canadian patients had hypodontia or hypogonadism, and none had peripheral nerve abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20640464+15851747+17159124" 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>Neuropathologic Features</em></strong></p><p>
<a href="#9" class="mim-tip-reference" title="Wolf, N. I., Vanderver, A., van Spaendonk, R. M. L., Schiffmann, R., Brais, B., Bugiani, M., Sistermans, E., Catsman-Berrevoets, C., Kros, J. M., Soares Pinto, P., Pohl, D., Tirupathi, S., and 10 others. &lt;strong&gt;Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations.&lt;/strong&gt; Neurology 83: 1898-1905, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25339210/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25339210&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25339210[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0000000000001002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25339210">Wolf et al. (2014)</a> reported the neuropathologic features of a 14-year-old girl with HLD7 who was homozygous for a Q599H mutation in the POLR3A gene. There was diffuse white matter atrophy with thin corpus callosum and enlarged ventricles, and the white matter was nonhomogeneously discolored. There was variable white matter rarefaction, lack of myelin, reduced numbers of oligodendrocytes, and foamy macrophages. Sural nerve from the patient showed mild lack of myelin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25339210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>The transmission pattern of HLD7 in the families reported by <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a> and <a href="#3" class="mim-tip-reference" title="Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B. &lt;strong&gt;Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.&lt;/strong&gt; Neurogenetics 11: 457-464, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20640464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20640464&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0251-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20640464">Bernard et al. (2010)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20640464+12605447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>By homozygosity mapping of several French Canadian families with a similar form of hypomyelinating leukodystrophy, <a href="#3" class="mim-tip-reference" title="Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B. &lt;strong&gt;Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.&lt;/strong&gt; Neurogenetics 11: 457-464, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20640464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20640464&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0251-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20640464">Bernard et al. (2010)</a> found linkage to a 12.6-Mb region between <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs7069982;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs7069982</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2071510;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs2071510</a> on chromosome 10q22.3-q23.31 (maximum lod score of 5.47 at markers D10S201, D10S1777, and D10S1696). Sequencing of candidate genes within the region did not reveal any pathogenic mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20640464" 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 genomewide linkage analysis of the Syrian family reported by <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a>, <a href="#4" class="mim-tip-reference" title="Chouery, E., Delague, V., Jalkh, N., Salem, N., Kfoury, J., Rodriguez, D., Chabrol, B., Boespflug-Tanguy, O., Levy, N., Serre, J. L., Megarbane, A. &lt;strong&gt;A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22.&lt;/strong&gt; Neurogenetics 12: 73-78, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20721593/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20721593&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0256-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20721593">Chouery et al. (2011)</a> identified an 8.7-Mb region on chromosome 10q22.1-q23.33 (maximum multipoint lod score of 5.66 between SNPs <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10823772;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10823772</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs927452;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs927452</a>) as harboring the candidate gene. Sequencing of candidate genes within the region did not reveal any pathogenic mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12605447+20721593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>By narrowing the candidate disease locus followed by direct sequencing of the genes in the refined 2.99-Mb interval in several families with hypomyelinating leukodystrophy mapping to chromosome 10q22, <a href="#2" class="mim-tip-reference" title="Bernard, G., Chouery, E., Putorti, M. L., Tetreault, M., Takanohashi, A., Carosso, G., Clement, I., Boespflug-Tanguy, O., Rodriguez, D., Delague, V., Abou Ghoch, J., Jalkh, N., Dorboz, I., Fribourg, S., Teichmann, M., Megarbane, A., Schiffmann, R., Vanderver, A., Brais, B. &lt;strong&gt;Mutations of POLR3A encoding a catalytic subunit of RNA polymerase pol III cause a recessive hypomyelinating leukodystrophy.&lt;/strong&gt; Am. J. Hum. Genet. 89: 415-423, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 972 only, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21855841/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21855841&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21855841[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2011.07.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21855841">Bernard et al. (2011)</a> identified 14 different mutations in the POLR3A gene (see, e.g., <a href="/entry/614258#0001">614258.0001</a>-<a href="/entry/614258#0005">614258.0005</a>). All mutations were in the homozygous or compound heterozygous state, and no patient had 2 truncating mutations. There were 19 patients from 12 families, including those reported by <a href="#1" class="mim-tip-reference" title="Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A. &lt;strong&gt;Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?&lt;/strong&gt; Am. J. Med. Genet. 118A: 76-81, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12605447/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12605447&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.10019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12605447">Atrouni et al. (2003)</a>, <a href="#6" class="mim-tip-reference" title="Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K. &lt;strong&gt;Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.&lt;/strong&gt; Neurology 67: 2066-2069, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17159124/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17159124&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17159124[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000247666.28904.35&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17159124">Timmons et al. (2006)</a>, and <a href="#3" class="mim-tip-reference" title="Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B. &lt;strong&gt;Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.&lt;/strong&gt; Neurogenetics 11: 457-464, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20640464/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20640464&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10048-010-0251-8&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20640464">Bernard et al. (2010)</a>. The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder. <a href="#2" class="mim-tip-reference" title="Bernard, G., Chouery, E., Putorti, M. L., Tetreault, M., Takanohashi, A., Carosso, G., Clement, I., Boespflug-Tanguy, O., Rodriguez, D., Delague, V., Abou Ghoch, J., Jalkh, N., Dorboz, I., Fribourg, S., Teichmann, M., Megarbane, A., Schiffmann, R., Vanderver, A., Brais, B. &lt;strong&gt;Mutations of POLR3A encoding a catalytic subunit of RNA polymerase pol III cause a recessive hypomyelinating leukodystrophy.&lt;/strong&gt; Am. J. Hum. Genet. 89: 415-423, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 972 only, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21855841/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21855841&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21855841[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2011.07.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21855841">Bernard et al. (2011)</a> hypothesized that POLR3A mutations lead to dysregulation of RNA polymerase III and its targets, resulting in decreased expression of certain tRNAs during development and impaired protein synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21855841+17159124+12605447+20640464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
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<strong>Genotype/Phenotype Correlations</strong>
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<p><a href="#9" class="mim-tip-reference" title="Wolf, N. I., Vanderver, A., van Spaendonk, R. M. L., Schiffmann, R., Brais, B., Bugiani, M., Sistermans, E., Catsman-Berrevoets, C., Kros, J. M., Soares Pinto, P., Pohl, D., Tirupathi, S., and 10 others. &lt;strong&gt;Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations.&lt;/strong&gt; Neurology 83: 1898-1905, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25339210/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25339210&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25339210[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0000000000001002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25339210">Wolf et al. (2014)</a> performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Most patients of French Canadian descent carried the G672E mutation (<a href="/entry/614258#0001">614258.0001</a>). Except for the French Canadian patients, most patients of European descent carried POLR3B mutations. Among all patients, about half had delayed development, including 19 (17%) who were never able to walk independently (4 with POLR3A mutations and 15 and POLR3B mutations). Ten (10%) of patients presented after age 10 years. All patients except one, who was older at the time of diagnosis, had cerebellar signs, such as severe intention tremor, dysmetria, ataxia, abnormal smooth pursuit, and nystagmus. Deterioration of speech and swallowing occurred later. Only a few patients had extrapyramidal signs, mainly dystonia. Cognition varied widely from normal in a few patients to moderate intellectual disability in most. About 20% of patients had seizures. Neurologic deterioration with infection occurred in about half of patients. Dental abnormalities, such as delayed dentition and hypodontia, were common (in 87%). Delayed puberty, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations. Most (87%) patients had severe and often progressive myopia, and about half had short stature. Growth hormone deficiency was found in 5 of 10 patients tested. Brain imaging showed hypomyelination in all patients and cerebellar atrophy in most. Supratentorial atrophy and thin corpus callosum were seen in older patients, reflecting white matter loss. A T2-weighted hypodense dot in the posterior limb of the internal capsule was seen in 70% of patients with POLR3B mutations, but only 13% of those with POLR3A mutations. In general, patients with POLR3A mutations had a more severe disease than those with POLR3B mutations. Two sibs with a homozygous POLR3B V523E mutation (<a href="/entry/614366#0005">614366.0005</a>) had an exceptionally mild clinical course. <a href="#9" class="mim-tip-reference" title="Wolf, N. I., Vanderver, A., van Spaendonk, R. M. L., Schiffmann, R., Brais, B., Bugiani, M., Sistermans, E., Catsman-Berrevoets, C., Kros, J. M., Soares Pinto, P., Pohl, D., Tirupathi, S., and 10 others. &lt;strong&gt;Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations.&lt;/strong&gt; Neurology 83: 1898-1905, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25339210/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25339210&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25339210[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0000000000001002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25339210">Wolf et al. (2014)</a> concluded that 4H syndrome is an insidiously progressive neurologic disorder with declining motor function of variable severity, but dental abnormalities and hypogonadism are not obligatory for the diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25339210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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</h4>
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<p />
</div>
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<a id="1" class="mim-anchor"></a>
<a id="Atrouni2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A.
<strong>Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?</strong>
Am. J. Med. Genet. 118A: 76-81, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12605447/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12605447</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12605447" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.10019" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Bernard2011" class="mim-anchor"></a>
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<p class="mim-text-font">
Bernard, G., Chouery, E., Putorti, M. L., Tetreault, M., Takanohashi, A., Carosso, G., Clement, I., Boespflug-Tanguy, O., Rodriguez, D., Delague, V., Abou Ghoch, J., Jalkh, N., Dorboz, I., Fribourg, S., Teichmann, M., Megarbane, A., Schiffmann, R., Vanderver, A., Brais, B.
<strong>Mutations of POLR3A encoding a catalytic subunit of RNA polymerase pol III cause a recessive hypomyelinating leukodystrophy.</strong>
Am. J. Hum. Genet. 89: 415-423, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 972 only, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21855841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21855841</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21855841[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=21855841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2011.07.014" target="_blank">Full Text</a>]
</p>
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<a id="Bernard2010" class="mim-anchor"></a>
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<p class="mim-text-font">
Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B.
<strong>Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.</strong>
Neurogenetics 11: 457-464, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20640464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20640464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20640464[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=20640464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10048-010-0251-8" target="_blank">Full Text</a>]
</p>
</div>
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<a id="4" class="mim-anchor"></a>
<a id="Chouery2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chouery, E., Delague, V., Jalkh, N., Salem, N., Kfoury, J., Rodriguez, D., Chabrol, B., Boespflug-Tanguy, O., Levy, N., Serre, J. L., Megarbane, A.
<strong>A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22.</strong>
Neurogenetics 12: 73-78, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20721593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20721593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20721593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10048-010-0256-3" target="_blank">Full Text</a>]
</p>
</div>
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<a id="5" class="mim-anchor"></a>
<a id="Saitsu2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Saitsu, H., Osaka, H., Sasaki, M., Takanashi, J., Hamada, K., Yamashita, A., Shibayama, H., Shiina, M., Kondo, Y., Nishiyama, K., Tsurusaki, Y., Miyake, N., Doi, H., Ogata, K., Inoue, K., Matsumoto, N.
<strong>Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy.</strong>
Am. J. Hum. Genet. 89: 644-651, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22036171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22036171</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22036171[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=22036171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ajhg.2011.10.003" target="_blank">Full Text</a>]
</p>
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<a id="Timmons2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K.
<strong>Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.</strong>
Neurology 67: 2066-2069, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17159124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17159124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17159124[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=17159124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.wnl.0000247666.28904.35" target="_blank">Full Text</a>]
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<a id="Wolf2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wolf, N. I., Harting, I., Boltshauser, E., Wiegand, G., Koch, M. J., Schmitt-Mechelke, T., Martin, E., Zschocke, J., Uhlenberg, B., Hoffmann, G. F., Weber, L., Ebinger, F., Rating, D.
<strong>Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.</strong>
Neurology 64: 1461-1464, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15851747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15851747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15851747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/01.WNL.0000158615.56071.E3" target="_blank">Full Text</a>]
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<a id="Wolf2007" class="mim-anchor"></a>
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<p class="mim-text-font">
Wolf, N. I., Harting, I., Innes, A. M., Parzer, S., Zeitler, P., Schneider, A., Wolff, A., Baier, K., Zschocke, J., Ebinger, F., Boltshauser, E., Rating, D.
<strong>Ataxia, delayed dentition and hypomyelination: a novel leukoencephalopathy.</strong>
Neuropediatrics 38: 64-70, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17712733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17712733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17712733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1055/s-2007-985137" target="_blank">Full Text</a>]
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<a id="Wolf2014" class="mim-anchor"></a>
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Wolf, N. I., Vanderver, A., van Spaendonk, R. M. L., Schiffmann, R., Brais, B., Bugiani, M., Sistermans, E., Catsman-Berrevoets, C., Kros, J. M., Soares Pinto, P., Pohl, D., Tirupathi, S., and 10 others.
<strong>Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations.</strong>
Neurology 83: 1898-1905, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25339210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25339210</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25339210[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=25339210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/WNL.0000000000001002" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 9/8/2015
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Cassandra L. Kniffin - updated : 12/7/2011<br>Cassandra L. Kniffin - updated : 10/3/2011
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Creation Date:
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Victor A. McKusick : 4/17/2003
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carol : 06/05/2024
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carol : 02/04/2022<br>carol : 02/04/2022<br>carol : 02/03/2022<br>carol : 01/21/2020<br>carol : 10/19/2016<br>alopez : 09/15/2015<br>alopez : 9/15/2015<br>ckniffin : 9/8/2015<br>carol : 10/1/2013<br>carol : 12/8/2011<br>ckniffin : 12/7/2011<br>carol : 10/3/2011<br>carol : 10/3/2011<br>ckniffin : 10/3/2011<br>wwang : 12/3/2008<br>ckniffin : 12/2/2008<br>carol : 4/17/2003<br>carol : 4/17/2003
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<strong>#</strong> 607694
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LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD7
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<em>Alternative titles; symbols</em>
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LEUKOENCEPHALOPATHY, HYPOMYELINATING, WITH ATAXIA AND DELAYED DENTITION<br />
ATAXIA, DELAYED DENTITION, AND HYPOMYELINATION; ADDH<br />
LEUKODYSTROPHY, HYPOMYELINATING, WITH HYPODONTIA AND HYPOGONADOTROPIC HYPOGONADISM<br />
4H SYNDROME<br />
4H LEUKODYSTROPHY 1
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<strong>SNOMEDCT:</strong> 721846006; &nbsp;
<strong>ICD10CM:</strong> G11.5; &nbsp;
<strong>ORPHA:</strong> 137639, 447893, 447896, 77295, 88637; &nbsp;
<strong>DO:</strong> 0060794; &nbsp;
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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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10q22.3
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Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism
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607694
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Autosomal recessive
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3
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POLR3A
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614258
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that hypomyelinating leukodystrophy-7 (HLD7) is caused by homozygous or compound heterozygous mutation in the POLR3A gene (614258) on chromosome 10q22.</p>
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<strong>Description</strong>
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<p>Hypomyelinating leukodystrophy-7 (HLD7) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability (summary by Bernard et al., 2011). </p><p>See also HLD8 (614381), which has similar features and is caused by mutation in the POLR3B gene (614366) on chromosome 12q23. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.</p>
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<strong>Clinical Features</strong>
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<p>In an inbred Syrian pedigree, Atrouni et al. (2003) described oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome. Age at onset was about 12 years. Abnormalities in the white matter and cortical atrophy were demonstrated by magnetic resonance imaging. In 1 sibship of 8, 3 girls and a boy were affected; the parents were consanguineous. Atrouni et al. (2003) suggested that this might represent a distinct form of dentoleukoencephalopathy with autosomal recessive inheritance. </p><p>Wolf et al. (2005) reported 4 unrelated German or Swiss girls with early onset of progressive ataxia during the second year of life, mild to moderate brain hypomyelination, cerebellar atrophy, and delayed dentition. The first teeth to appear were the deciduous molars. Some patients were missing permanent teeth. All patients also had short stature. Wolf et al. (2005) considered the disorder clinically distinct from that reported by Atrouni et al. (2003) because in the Syrian pedigree the MRI did not show hypomyelination, but demyelination mainly of the pyramidal tracts and of the subcortical matter, the onset of ataxia occurred after the age of 10 years, and the pattern of tooth agenesis was different. </p><p>Wolf et al. (2007) reported 4 additional patients, including 3 boys, with ataxia, delayed dentition, and hypomyelination similar to their earlier report. All had delayed motor development with early-onset ataxia, tremor, dysarthria, and hypometric saccades. Pyramidal signs were variable, and most had mild cognitive dysfunction. Two patients had neonatal teeth, and all showed delayed dentition and abnormal order of tooth eruption. MRI showed hypomyelination of the supratentorial white matter, with thin corpus callosum and cerebellar atrophy. </p><p>Saitsu et al. (2011) reported a 17-year-old Japanese boy with HLD7 confirmed by genetic analysis (614258.0006 and 614258.0007). He showed normal development until age 4, when mild tremors were noted. He later developed cerebellar signs, including expressive ataxic speech, intention tremor, poor finger-to-nose test, dysdiadochokinesis, dysmetria, and wide-based ataxic gait. He also showed intellectual disability with an IQ of 57. Other features included severe myopia and unilateral sensorineural deafness. The motor deterioration was progressive, and he became wheelchair-bound around age 14 years. Brain MRI showed a hypoplastic corpus callosum, cerebellar atrophy, and white matter lesions in the basal ganglia. He did not have hypodontia or hypogonadism. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Timmons et al. (2006) reported 4 unrelated patients with delayed tooth eruption and hypodontia of permanent teeth. Three patients were otherwise normal until age 12 years, when progressive hypomyelination and dysmyelination resulted in ataxia, dysmetria, spasticity, dysarthria, and extensor plantar responses. The fourth patient had onset at age 7. None of the patients had spontaneous puberty due to hypogonadotropic hypogonadism. There were also cognitive deficits. Sural nerve biopsy showed granular debris-lined clefts, expanded abaxonal space, vacuolar disruption, and loss of normal myelin periodicity. Brain MRI showed central hypomyelination and cerebellar atrophy. Timmons et al. (2006) proposed the designation '4H syndrome.' </p><p>Bernard et al. (2010) reported 6 living patients and 1 deceased patient from 5 French Canadian families with a similar form of very early childhood-onset hypomyelinating leukodystrophy. Two of the families were consanguineous. The average age at onset was 2.5 years (range 1 to 5) and all presented with motor regression, ataxia, tremor, and spasticity. Other features included dysarthria, hyperreflexia, extensor plantar responses, abnormal bladder function, abnormal saccades, and nystagmus. Most became wheelchair-bound by later childhood. Less common features included dysphagia, drooling, optic atrophy, and complex partial seizures. Cognitive decline was mild, but noticeable. Two of 7 patients had some degree of hypodontia, and 1 had hypogonadotropic hypogonadism. Bernard et al. (2010) recognized the phenotypic overlap with the patients reported by Wolf et al. (2005) and Timmons et al. (2006), but noted that not all the French Canadian patients had hypodontia or hypogonadism, and none had peripheral nerve abnormalities. </p><p><strong><em>Neuropathologic Features</em></strong></p><p>
Wolf et al. (2014) reported the neuropathologic features of a 14-year-old girl with HLD7 who was homozygous for a Q599H mutation in the POLR3A gene. There was diffuse white matter atrophy with thin corpus callosum and enlarged ventricles, and the white matter was nonhomogeneously discolored. There was variable white matter rarefaction, lack of myelin, reduced numbers of oligodendrocytes, and foamy macrophages. Sural nerve from the patient showed mild lack of myelin. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of HLD7 in the families reported by Atrouni et al. (2003) and Bernard et al. (2010) was consistent with autosomal recessive inheritance. </p>
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<strong>Mapping</strong>
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<p>By homozygosity mapping of several French Canadian families with a similar form of hypomyelinating leukodystrophy, Bernard et al. (2010) found linkage to a 12.6-Mb region between rs7069982 and rs2071510 on chromosome 10q22.3-q23.31 (maximum lod score of 5.47 at markers D10S201, D10S1777, and D10S1696). Sequencing of candidate genes within the region did not reveal any pathogenic mutations. </p><p>By genomewide linkage analysis of the Syrian family reported by Atrouni et al. (2003), Chouery et al. (2011) identified an 8.7-Mb region on chromosome 10q22.1-q23.33 (maximum multipoint lod score of 5.66 between SNPs rs10823772 and rs927452) as harboring the candidate gene. Sequencing of candidate genes within the region did not reveal any pathogenic mutations. </p>
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<strong>Molecular Genetics</strong>
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<p>By narrowing the candidate disease locus followed by direct sequencing of the genes in the refined 2.99-Mb interval in several families with hypomyelinating leukodystrophy mapping to chromosome 10q22, Bernard et al. (2011) identified 14 different mutations in the POLR3A gene (see, e.g., 614258.0001-614258.0005). All mutations were in the homozygous or compound heterozygous state, and no patient had 2 truncating mutations. There were 19 patients from 12 families, including those reported by Atrouni et al. (2003), Timmons et al. (2006), and Bernard et al. (2010). The mutations were spread throughout the gene, and there were no obvious genotype/phenotype correlations. Immunoblot analysis showed decreased levels of POLR3A protein in fibroblasts from 4 affected individuals, and decreased levels in the cortex and cerebral white matter of another patient, suggesting that loss of function is responsible for the disorder. Bernard et al. (2011) hypothesized that POLR3A mutations lead to dysregulation of RNA polymerase III and its targets, resulting in decreased expression of certain tRNAs during development and impaired protein synthesis. </p>
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<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
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<p>Wolf et al. (2014) performed a cross-sectional observational study of 105 patients with 4H syndrome, including 43 with mutations in the POLR3A gene and 62 with mutations in the POLR3B gene. Most patients of French Canadian descent carried the G672E mutation (614258.0001). Except for the French Canadian patients, most patients of European descent carried POLR3B mutations. Among all patients, about half had delayed development, including 19 (17%) who were never able to walk independently (4 with POLR3A mutations and 15 and POLR3B mutations). Ten (10%) of patients presented after age 10 years. All patients except one, who was older at the time of diagnosis, had cerebellar signs, such as severe intention tremor, dysmetria, ataxia, abnormal smooth pursuit, and nystagmus. Deterioration of speech and swallowing occurred later. Only a few patients had extrapyramidal signs, mainly dystonia. Cognition varied widely from normal in a few patients to moderate intellectual disability in most. About 20% of patients had seizures. Neurologic deterioration with infection occurred in about half of patients. Dental abnormalities, such as delayed dentition and hypodontia, were common (in 87%). Delayed puberty, in those old enough to assess, occurred in 81% of patients with POLR3A mutations and in 69% of those with POLR3B mutations. Most (87%) patients had severe and often progressive myopia, and about half had short stature. Growth hormone deficiency was found in 5 of 10 patients tested. Brain imaging showed hypomyelination in all patients and cerebellar atrophy in most. Supratentorial atrophy and thin corpus callosum were seen in older patients, reflecting white matter loss. A T2-weighted hypodense dot in the posterior limb of the internal capsule was seen in 70% of patients with POLR3B mutations, but only 13% of those with POLR3A mutations. In general, patients with POLR3A mutations had a more severe disease than those with POLR3B mutations. Two sibs with a homozygous POLR3B V523E mutation (614366.0005) had an exceptionally mild clinical course. Wolf et al. (2014) concluded that 4H syndrome is an insidiously progressive neurologic disorder with declining motor function of variable severity, but dental abnormalities and hypogonadism are not obligatory for the diagnosis. </p>
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<strong>REFERENCES</strong>
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<p class="mim-text-font">
Atrouni, S., Daraze, A., Tamraz, J., Cassia, A., Caillaud, C., Megarbane, A.
<strong>Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity?</strong>
Am. J. Med. Genet. 118A: 76-81, 2003.
[PubMed: 12605447]
[Full Text: https://doi.org/10.1002/ajmg.a.10019]
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<li>
<p class="mim-text-font">
Bernard, G., Chouery, E., Putorti, M. L., Tetreault, M., Takanohashi, A., Carosso, G., Clement, I., Boespflug-Tanguy, O., Rodriguez, D., Delague, V., Abou Ghoch, J., Jalkh, N., Dorboz, I., Fribourg, S., Teichmann, M., Megarbane, A., Schiffmann, R., Vanderver, A., Brais, B.
<strong>Mutations of POLR3A encoding a catalytic subunit of RNA polymerase pol III cause a recessive hypomyelinating leukodystrophy.</strong>
Am. J. Hum. Genet. 89: 415-423, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 972 only, 2012.
[PubMed: 21855841]
[Full Text: https://doi.org/10.1016/j.ajhg.2011.07.014]
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<li>
<p class="mim-text-font">
Bernard, G., Thiffault, I., Tetreault, M., Putorti, M. L., Bouchard, I., Sylvain, M., Melancon, S., Laframboise, R., Langevin, P., Bouchard, J.-P., Vanasse, M., Vanderver, A., Sebire, G., Brais, B.
<strong>Tremor-ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3-10q23.31.</strong>
Neurogenetics 11: 457-464, 2010.
[PubMed: 20640464]
[Full Text: https://doi.org/10.1007/s10048-010-0251-8]
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Chouery, E., Delague, V., Jalkh, N., Salem, N., Kfoury, J., Rodriguez, D., Chabrol, B., Boespflug-Tanguy, O., Levy, N., Serre, J. L., Megarbane, A.
<strong>A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22.</strong>
Neurogenetics 12: 73-78, 2011.
[PubMed: 20721593]
[Full Text: https://doi.org/10.1007/s10048-010-0256-3]
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<li>
<p class="mim-text-font">
Saitsu, H., Osaka, H., Sasaki, M., Takanashi, J., Hamada, K., Yamashita, A., Shibayama, H., Shiina, M., Kondo, Y., Nishiyama, K., Tsurusaki, Y., Miyake, N., Doi, H., Ogata, K., Inoue, K., Matsumoto, N.
<strong>Mutations in POLR3A and POLR3B encoding RNA polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy.</strong>
Am. J. Hum. Genet. 89: 644-651, 2011.
[PubMed: 22036171]
[Full Text: https://doi.org/10.1016/j.ajhg.2011.10.003]
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</li>
<li>
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Timmons, M., Tsokos, M., Abu Asab, M., Seminara, S. B., Zirzow, G. C., Kaneski, C. R., Heiss, J. D., van der Knaap, M. S., Vanier, M. T., Schiffmann, R., Wong, K.
<strong>Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.</strong>
Neurology 67: 2066-2069, 2006.
[PubMed: 17159124]
[Full Text: https://doi.org/10.1212/01.wnl.0000247666.28904.35]
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<li>
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Wolf, N. I., Harting, I., Boltshauser, E., Wiegand, G., Koch, M. J., Schmitt-Mechelke, T., Martin, E., Zschocke, J., Uhlenberg, B., Hoffmann, G. F., Weber, L., Ebinger, F., Rating, D.
<strong>Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.</strong>
Neurology 64: 1461-1464, 2005.
[PubMed: 15851747]
[Full Text: https://doi.org/10.1212/01.WNL.0000158615.56071.E3]
</p>
</li>
<li>
<p class="mim-text-font">
Wolf, N. I., Harting, I., Innes, A. M., Parzer, S., Zeitler, P., Schneider, A., Wolff, A., Baier, K., Zschocke, J., Ebinger, F., Boltshauser, E., Rating, D.
<strong>Ataxia, delayed dentition and hypomyelination: a novel leukoencephalopathy.</strong>
Neuropediatrics 38: 64-70, 2007.
[PubMed: 17712733]
[Full Text: https://doi.org/10.1055/s-2007-985137]
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</li>
<li>
<p class="mim-text-font">
Wolf, N. I., Vanderver, A., van Spaendonk, R. M. L., Schiffmann, R., Brais, B., Bugiani, M., Sistermans, E., Catsman-Berrevoets, C., Kros, J. M., Soares Pinto, P., Pohl, D., Tirupathi, S., and 10 others.
<strong>Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations.</strong>
Neurology 83: 1898-1905, 2014.
[PubMed: 25339210]
[Full Text: https://doi.org/10.1212/WNL.0000000000001002]
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Cassandra L. Kniffin - updated : 9/8/2015<br>Cassandra L. Kniffin - updated : 12/7/2011<br>Cassandra L. Kniffin - updated : 10/3/2011
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