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<title>
Entry
- #255320 - CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE; CMYO1B
- OMIM
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<span class="h4">#255320</span>
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<strong>Table of Contents</strong>
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<li role="presentation">
<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/255320"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS117000"> <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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<li role="presentation" style="margin-left: 1em">
<a href="#populationGenetics">Population Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE) OR (RYR1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></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=698&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Multiminicore myopathy&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=13922&Typ=Pat" title="Congenital multicore myopathy with external ophthalmoplegia" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Congenital multicore myopa…&nbsp;</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/4818" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Multiminicore myopathy</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98905" title="Congenital multicore myopathy with external ophthalmoplegia" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Congenital multicore myopa…</a></div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0080991" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<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>ICD10CM:</strong> G71.29<br />
<strong>ORPHA:</strong> 598, 98905<br />
<strong>DO:</strong> 0080991<br />
">ICD+</a>
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<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
255320
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<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE; CMYO1B
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<em>Alternative titles; symbols</em>
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<h4>
<span class="mim-font">
MINICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA<br />
MINICORE MYOPATHY<br />
MULTICORE MYOPATHY<br />
MULTIMINICORE MYOPATHY<br />
MULTICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA<br />
MULTIMINICORE DISEASE WITH EXTERNAL OPHTHALMOPLEGIA
</span>
</h4>
</div>
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<br />
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<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
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</h4>
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<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/19/649?start=-3&limit=10&highlight=649">
19q13.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Congenital myopathy 1B, autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255320"> 255320 </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">
RYR1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180901"> 180901 </a>
</span>
</td>
</tr>
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<a href="/phenotypicSeries/PS117000" class="btn btn-info" role="button"> Phenotypic Series </a>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/255320" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
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<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Facial weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95666008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95666008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R29.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R29.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.83</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/781.94" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.94</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007209</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span><br /> -
Myopathic facies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26432009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26432009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0332615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332615</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- External ophthalmoplegia affecting upward and lateral gaze <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850675&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850675</a>]</span><br /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- High-arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br /> -
Inverted V-shaped mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845453</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Frequent respiratory infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806482&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806482</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span><br /> -
Respiratory insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409622000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409622000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J96.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J96.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1145670&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1145670</a>, <a href="https://bioportal.bioontology.org/search?q=C0035229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035229</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002878" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002878</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span><br /> -
Respiratory impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035229</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>]</span><br /> -
Lung hypoplasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80825009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80825009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265783&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265783</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002089</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002089</a>]</span><br />
</span>
</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">
- Feeding difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Ligamentous laxity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27911000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27911000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/728.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">728.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158359&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158359</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001382" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001382</a>]</span><br /> -
Contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57048009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57048009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55033002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55033002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009917</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Scoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/298382003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">298382003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20944008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20944008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111266001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111266001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0559260&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0559260</a>, <a href="https://bioportal.bioontology.org/search?q=C0036439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036439</a>, <a href="https://bioportal.bioontology.org/search?q=C0700208&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700208</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002650" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002650</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hip dislocation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/157265008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">157265008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/S73.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">S73.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/835" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">835</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019554&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019554</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002827" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002827</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002827" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002827</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia, neonatal <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205294008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2267233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2267233</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001319</a>]</span><br /> -
Proximal muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249939004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221629</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003701" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003701</a>]</span><br /> -
Axial muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843697</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003327</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003327" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003327</a>]</span><br /> -
Muscle weakness, diffuse <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/728.87" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">728.87</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0746674&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0746674</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003324</a>]</span><br /> -
Muscle atrophy, limb-girdle and proximal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850679&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850679</a>]</span><br /> -
Exercise-induced myalgia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850830&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850830</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span><br /> -
Difficulty running or inability to run <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850681&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850681</a>]</span><br /> -
Walking may be limited <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850682&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850682</a>]</span><br /> -
Myopathic changes, nonspecific, seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4228976&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4228976</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/129565002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">129565002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G72.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M60-M63" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M60-M63</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/359.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">359.9</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003198" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003198</a>]</span><br /> -
Merosin-positive biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843699&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843699</a>]</span><br /> -
Focal loss of cross striations seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231066</a>]</span><br /> -
Disorganization of the myofibrillar pattern <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850686</a>]</span><br /> -
Variation in muscle fiber size <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843700&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843700</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003557" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003557</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003557" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003557</a>]</span><br /> -
Increased central nucleation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850687&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850687</a>]</span><br /> -
Increased connective tissue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866021&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866021</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009025</a>]</span><br /> -
Type 1 fiber atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850688&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850688</a>]</span><br /> -
Type 1 fiber predominance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673678</a>]</span><br /> -
Type 2 fiber hypertrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278547&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278547</a>]</span><br /> -
Fiber type disproportion <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/240084007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">240084007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0546264&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0546264</a>]</span><br /> -
Type 1 and type 2 muscle fibers with 'minicore' regions of sarcomeric disorganization, lack of oxidative activity, and absent mitochondria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843701&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843701</a>]</span><br /> -
Minicores extend full fiber diameter <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850689&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850689</a>]</span><br /> -
Minicore regions are poorly defined and do not extend through entire fiber length <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843702&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843702</a>]</span><br /> -
Dystrophic changes may be present <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843703&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843703</a>]</span><br /> -
Z-line streaming seen on electron microscopy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4478279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4478279</a>]</span><br /> -
Nemaline rods (rare) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808039</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003798" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003798</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003798" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003798</a>]</span><br /> -
Greater sartorius involvement than gracilis involvement seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806470&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806470</a>]</span><br /> -
Greater soleus involvement than gastrocnemii involvement seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806471&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806471</a>]</span><br /> -
Relative sparing of the rectus femoris <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012153&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012153</a>]</span><br /> -
Relative sparing of the tibialis anterior <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4012154&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4012154</a>]</span><br />
</span>
</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">
- Delayed motor development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br /> -
Some patients only achieve sitting <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278546&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278546</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">
- Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Movement </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Reduced fetal movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276369006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276369006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.8190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.8190</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/O36.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O36.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235659&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235659</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001558" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001558</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Amniotic Fluid </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hydrops <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/79654002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">79654002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267038008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267038008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20741006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20741006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R60.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R60.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/782.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">782.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013604&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013604</a>, <a href="https://bioportal.bioontology.org/search?q=C1058427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1058427</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000969" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000969</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000969" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000969</a>]</span><br /> -
Polyhydramnios <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86203003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86203003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/657.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">657.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/657" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">657</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001561" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001561</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001561" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001561</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Normal serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850678</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 neonatal period or early infancy<br /> -
Highly variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839039</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
Some patients have lethal fetal akinesia with death in utero<br /> -
Findings in muscle biopsy may be variable<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 ryanodine receptor-1 gene (RYR1, <a href="/entry/180901#0021">180901.0021</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>
Myopathy, congenital (see also nemaline myopathy (<a href="/phenotypicSeries/PS161800">PS161800</a>), myofibrillar myopathy (<a href="/phenotypicSeries/PS601419">PS601419</a>), and centronuclear myopathy (<a href="/phenotypicSeries/PS160150">PS160150</a>)
- <a href="/phenotypicSeries/PS117000">PS117000</a>
- 33 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/1/217?start=-3&limit=10&highlight=217"> 1p36.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618578"> Congenital myopathy 19 </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/618578"> 618578 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/167410"> PAX7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/167410"> 167410 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/303?start=-3&limit=10&highlight=303"> 1p36.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/602771"> Congenital myopathy 3 with rigid spine </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/602771"> 602771 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606210"> SELENON </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606210"> 606210 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/741?start=-3&limit=10&highlight=741"> 1p31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620326"> Congenital myopathy 21 with early respiratory failure </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/620326"> 620326 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611327"> DNAJB4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611327"> 611327 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1184?start=-3&limit=10&highlight=1184"> 1q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255310"> Congenital myopathy 4A, autosomal dominant </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/255310"> 255310 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> TPM3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> 191030 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1184?start=-3&limit=10&highlight=1184"> 1q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609284"> Congenital myopathy 4B, autosomal recessive </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/609284"> 609284 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> TPM3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> 191030 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1558?start=-3&limit=10&highlight=1558"> 1q32.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620246"> Congenital myopathy 18 due to dihydropyridine receptor defect </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/620246"> 620246 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/114208"> CACNA1S </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/114208"> 114208 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1785?start=-3&limit=10&highlight=1785"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620278"> Congenital myopathy 2C, severe infantile, autosomal dominant </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/620278"> 620278 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> ACTA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> 102610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1785?start=-3&limit=10&highlight=1785"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620265"> Congenital myopathy 2B, severe infantile, autosomal recessive </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/620265"> 620265 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> ACTA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> 102610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1785?start=-3&limit=10&highlight=1785"> 1q42.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/161800"> Congenital myopathy 2A, typical, autosomal dominant </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/161800"> 161800 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> ACTA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102610"> 102610 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1828?start=-3&limit=10&highlight=1828"> 1q43 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618654"> Congenital myopathy 8 </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/618654"> 618654 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102573"> ACTN2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/102573"> 102573 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/823?start=-3&limit=10&highlight=823"> 2q31.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611705"> Congenital myopathy 5 with 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/611705"> 611705 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188840"> TTN </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/188840"> 188840 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/973?start=-3&limit=10&highlight=973"> 2q34 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618414"> Congenital myopathy 14 </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/618414"> 618414 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160780"> MYL1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160780"> 160780 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/887?start=-3&limit=10&highlight=887"> 3q26.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618823"> Congenital myopathy 9B, proximal, with minicore lesions </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/618823"> 618823 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600819"> FXR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600819"> 600819 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/887?start=-3&limit=10&highlight=887"> 3q26.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618822"> ?Congenital myopathy 9A with respiratory insufficiency and bone fractures </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/618822"> 618822 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600819"> FXR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600819"> 600819 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/410?start=-3&limit=10&highlight=410"> 5q23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620249"> Congenital myopathy 10B, mild variant </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/620249"> 620249 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612453"> MEGF10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612453"> 612453 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/410?start=-3&limit=10&highlight=410"> 5q23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614399"> Congenital myopathy 10A, severe variant </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/614399"> 614399 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612453"> MEGF10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612453"> 612453 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/350?start=-3&limit=10&highlight=350"> 8q21.11 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620964"> Congenital myopathy 25 </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/620964"> 620964 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605266"> JPH1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605266"> 605266 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/172?start=-3&limit=10&highlight=172"> 9p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609285"> Congenital myopathy 23 </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/609285"> 609285 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/190990"> TPM2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/190990"> 190990 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/84?start=-3&limit=10&highlight=84"> 10p12.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619967"> Congenital myopathy 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/619967"> 619967 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610467"> HACD1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610467"> 610467 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/10/239?start=-3&limit=10&highlight=239"> 10q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617336"> Congenital myopathy 24 </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/617336"> 617336 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608517"> MYPN </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608517"> 608517 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/212?start=-3&limit=10&highlight=212"> 11p15.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618975"> Congenital myopathy 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/618975"> 618975 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/159970"> MYOD1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/159970"> 159970 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/292?start=-3&limit=10&highlight=292"> 12q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612540"> Congenital myopathy 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/612540"> 612540 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600016"> CNTN1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600016"> 600016 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/536?start=-3&limit=10&highlight=536"> 12q13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255995"> Congenital myopathy 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/255995"> 255995 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615521"> STAC3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615521"> 615521 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/728?start=-3&limit=10&highlight=728"> 12q23.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618524"> Congenital myopathy 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/618524"> 618524 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160794"> MYBPC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160794"> 160794 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/92?start=-3&limit=10&highlight=92"> 14q11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255160"> Congenital myopathy 7B, myosin storage, autosomal recessive </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/255160"> 255160 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160760"> MYH7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160760"> 160760 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/14/92?start=-3&limit=10&highlight=92"> 14q11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608358"> Congenital myopathy 7A, myosin storage, autosomal dominant </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/608358"> 608358 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160760"> MYH7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160760"> 160760 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/63?start=-3&limit=10&highlight=63"> 15q13.3-q14 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620310"> Congenital myopathy 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/620310"> 620310 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180903"> RYR3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180903"> 180903 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/226?start=-3&limit=10&highlight=226"> 17p13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605637"> Congenital myopathy 6 with ophthalmoplegia </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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/605637"> 605637 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160740"> MYH2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/160740"> 160740 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/852?start=-3&limit=10&highlight=852"> 17q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620369"> Congenital myopathy 22B, severe fetal </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/620369"> 620369 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603967"> SCN4A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603967"> 603967 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/852?start=-3&limit=10&highlight=852"> 17q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620351"> Congenital myopathy 22A, classic </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/620351"> 620351 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603967"> SCN4A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603967"> 603967 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/649?start=-3&limit=10&highlight=649"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255320"> Congenital myopathy 1B, autosomal recessive </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/255320"> 255320 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180901"> RYR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180901"> 180901 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/649?start=-3&limit=10&highlight=649"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/117000"> Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia </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/117000"> 117000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180901"> RYR1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/180901"> 180901 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/20/342?start=-3&limit=10&highlight=342"> 20q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620161"> Congenital myopathy 15 </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/620161"> 620161 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191039"> TNNC2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191039"> 191039 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="text" class="mim-anchor"></a>
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
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</span>
</h4>
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<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that autosomal recessive congenital myopathy-1B (CMYO1B) is caused by homozygous or compound heterozygous mutation in the RYR1 gene (<a href="/entry/180901">180901</a>) on chromosome 19q13.</p><p>Heterozygous mutation in the RYR1 gene causes autosomal dominant CMYO1A (<a href="/entry/117000">117000</a>), which shows clinical overlap with CMYO1B, but is less severe.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Congenital myopathy-1B (CMYO1B) is an autosomal recessive disorder of skeletal muscle characterized by severe hypotonia and generalized muscle weakness apparent soon after birth or in early childhood with delayed motor development, generalized muscle weakness and atrophy, and difficulty walking or running. Affected individuals show proximal muscle weakness with axial and shoulder girdle involvement, external ophthalmoplegia, and bulbar weakness, often resulting in feeding difficulties and respiratory insufficiency. Orthopedic complications such as joint laxity, distal contractures, hip dislocation, cleft palate, and scoliosis are commonly observed. Serum creatine kinase is normal. The phenotype is variable in severity (<a href="#10" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. &lt;strong&gt;Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.&lt;/strong&gt; Neurology 65: 1930-1935, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16380615/&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;16380615&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000188870.37076.f2&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="16380615">Jungbluth et al., 2005</a>; <a href="#2" class="mim-tip-reference" title="Bharucha-Goebel, D. X., Santi, M., Medne, L., Zukosky, K., Dastgir, J., Shieh, P. B., Winder, T., Tennekoon, G., Finkel, R. S., Dowling, J. J., Monnier, N., Bonnemann, C. G. &lt;strong&gt;Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.&lt;/strong&gt; Neurology 80: 1584-1589, 2013. Note: Erratum: Neurology 80: 2081 only, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23553484/&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;23553484&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23553484[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.0b013e3182900380&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="23553484">Bharucha-Goebel et al., 2013</a>). Some patients show symptoms in utero, including reduced fetal movements, polyhydramnios, and intrauterine growth restriction. The most severely affected patients present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (<a href="#17" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. &lt;strong&gt;Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.&lt;/strong&gt; Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25476234/&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;25476234&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0&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="25476234">McKie et al., 2014</a>). Skeletal muscle biopsy of patients with recessive RYR1 mutations can show variable features, including multiminicores (<a href="#6" class="mim-tip-reference" title="Ferreiro, A., Fardeau, M. &lt;strong&gt;80th ENMC International Workshop on Multi-minicore Disease: 1st International MmD Workshop 12-13th May, 2000, Soestduinen, The Netherlands.&lt;/strong&gt; Neuromusc. Disord. 12: 60-68, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11731287/&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;11731287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(01)00237-1&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="11731287">Ferreiro and Fardeau, 2002</a>), central cores (<a href="#8" class="mim-tip-reference" title="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. &lt;strong&gt;Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.&lt;/strong&gt; Neurology 59: 284-287, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12136074/&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;12136074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.59.2.284&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="12136074">Jungbluth et al., 2002</a>), congenital fiber-type disproportion (CFTD) (<a href="#19" class="mim-tip-reference" title="Monnier, N., Laquerriere, A., Marret, S., Goldenberg, A., Marty, I., Nivoche, Y., Lunardi, J. &lt;strong&gt;First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia.&lt;/strong&gt; Neuromusc. Disord. 19: 680-684, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19734047/&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;19734047&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2009.07.007&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="19734047">Monnier et al., 2009</a>), and centronuclear myopathy (<a href="#24" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. &lt;strong&gt;RYR1 mutations are a common cause of congenital myopathies with central nuclei.&lt;/strong&gt; Ann. Neurol. 68: 717-726, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20839240/&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;20839240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22119&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="20839240">Wilmshurst et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23553484+19734047+12136074+11731287+16380615+20839240+25476234" 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>For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (<a href="/entry/117000">117000</a>).</p>
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<strong>Clinical Features</strong>
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<p><a href="#4" class="mim-tip-reference" title="Engel, A. G., Gomez, M. R., Groover, R. V. &lt;strong&gt;Multicore disease: a recently recognized congenital myopathy associated with multifocal degeneration of muscle fibres.&lt;/strong&gt; Mayo Clin. Proc. 46: 666-681, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5115748/&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;5115748&lt;/a&gt;]" pmid="5115748">Engel et al. (1971)</a> first reported multiminicore myopathy in 2 affected sibs. The disorder was a congenital myopathy associated with multifocal degeneration of muscle fibers on pathologic examination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5115748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bethlem, J., Arts, W. F., Dingemans, K. P. &lt;strong&gt;Common origin of rods, cores, miniature cores and focal loss of cross striations.&lt;/strong&gt; Arch. Neurol. 35: 555-566, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/687182/&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;687182&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1978.00500330003002&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="687182">Bethlem et al. (1978)</a> noted external ophthalmoplegia in 2 sibs (family C, patients 7 and 8) in whom muscle biopsies showed both multicores and focal loss of cross-striations. The family was also reported by <a href="#23" class="mim-tip-reference" title="Van Wijngaarden, G. K., Bethlem, J., Dingemans, K. P., Coers, C., Telerman-Toppet, N., Gerard, J. M. &lt;strong&gt;Familial focal loss of cross striations.&lt;/strong&gt; J. Neurol. 216: 163-172, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/72134/&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;72134&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00313617&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="72134">Van Wijngaarden et al. (1977)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=72134+687182" 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="#21" class="mim-tip-reference" title="Swash, M., Schwartz, M. S. &lt;strong&gt;Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.&lt;/strong&gt; J. Neurol. Sci. 52: 1-10, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7299413/&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;7299413&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90129-5&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="7299413">Swash and Schwartz (1981)</a> reported 2 brothers and a sister with a congenital myopathy characterized clinically by proximal weakness and external ophthalmoplegia and histologically by multicores and areas of focal loss of cross-striations in skeletal muscles. Both brothers showed highly arched palate. One brother, more severely affected than the other, developed respiratory failure in association with Mycoplasma pneumonia at age 14 years, and required mechanical ventilation for 3 days. Two other sisters and both parents were clinically normal. <a href="#21" class="mim-tip-reference" title="Swash, M., Schwartz, M. S. &lt;strong&gt;Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.&lt;/strong&gt; J. Neurol. Sci. 52: 1-10, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7299413/&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;7299413&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90129-5&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="7299413">Swash and Schwartz (1981)</a> noted the similarities to the phenotype described by <a href="#1" class="mim-tip-reference" title="Bethlem, J., Arts, W. F., Dingemans, K. P. &lt;strong&gt;Common origin of rods, cores, miniature cores and focal loss of cross striations.&lt;/strong&gt; Arch. Neurol. 35: 555-566, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/687182/&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;687182&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1978.00500330003002&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="687182">Bethlem et al. (1978)</a>. <a href="#21" class="mim-tip-reference" title="Swash, M., Schwartz, M. S. &lt;strong&gt;Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.&lt;/strong&gt; J. Neurol. Sci. 52: 1-10, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7299413/&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;7299413&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90129-5&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="7299413">Swash and Schwartz (1981)</a> pointed out that previously reported patients in whom ophthalmoplegia was associated with core-like lesions all had focal loss of cross-striations as a prominent feature, with or without multicores (<a href="#4" class="mim-tip-reference" title="Engel, A. G., Gomez, M. R., Groover, R. V. &lt;strong&gt;Multicore disease: a recently recognized congenital myopathy associated with multifocal degeneration of muscle fibres.&lt;/strong&gt; Mayo Clin. Proc. 46: 666-681, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5115748/&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;5115748&lt;/a&gt;]" pmid="5115748">Engel et al., 1971</a>; <a href="#23" class="mim-tip-reference" title="Van Wijngaarden, G. K., Bethlem, J., Dingemans, K. P., Coers, C., Telerman-Toppet, N., Gerard, J. M. &lt;strong&gt;Familial focal loss of cross striations.&lt;/strong&gt; J. Neurol. 216: 163-172, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/72134/&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;72134&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00313617&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="72134">Van Wijngaarden et al., 1977</a>; <a href="#1" class="mim-tip-reference" title="Bethlem, J., Arts, W. F., Dingemans, K. P. &lt;strong&gt;Common origin of rods, cores, miniature cores and focal loss of cross striations.&lt;/strong&gt; Arch. Neurol. 35: 555-566, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/687182/&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;687182&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1978.00500330003002&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="687182">Bethlem et al., 1978</a>), as in their patients. The authors regarded this disorder as a genetically distinct subtype of multicore disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5115748+7299413+72134+687182" 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>Among 19 cases of minicore myopathy, <a href="#9" class="mim-tip-reference" title="Jungbluth, H., Sewry, C., Brown, S. C., Manzur, A. Y., Mercuri, E., Bushby, K., Rowe, P., Johnson, M. A., Hughes, I., Kelsey, A., Dubowitz, V., Muntoni, F. &lt;strong&gt;Minicore myopathy in children: a clinical and histopathological study of 19 cases.&lt;/strong&gt; Neuromusc. Disord. 10: 264-273, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10838253/&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;10838253&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(99)00125-x&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="10838253">Jungbluth et al. (2000)</a> reported 2 with complete external ophthalmoplegia and a severe phenotype, including hypotonia and facial, axial, and proximal weakness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10838253" 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>Among 38 patients with histologically proven minicore myopathy, <a href="#5" class="mim-tip-reference" title="Ferreiro, A., Estournet, B., Chateau, D., Romero, N. B., Laroche, C., Odent, S., Toutain, A., Cabello, A., Fontan, D., dos Santos, H. G., Haenggeli, C.-A., Bertini, E., Urtizberea, J.-A., Guicheney, P., Fardeau, M. &lt;strong&gt;Multi-minicore disease-searching for boundaries: phenotype analysis of 38 cases.&lt;/strong&gt; Ann. Neurol. 48: 745-757, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11079538/&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;11079538&lt;/a&gt;]" pmid="11079538">Ferreiro et al. (2000)</a> reported 3 who had an antenatal-onset form with congenital generalized arthrogryposis, which the authors suggested was a distinct subtype of multiminicore disease. Other features included dolichocephaly, prominent nasal root, oblique palpebral fissures, high-arched palate, low-set ears, and short neck with mild pterygium colli. Two brothers also had a bell-shaped thorax, clinodactyly, bilateral cryptorchidism, and a single palmar crease. All 3 patients had moderate predominantly axial muscle weakness, early severe kyphosis or kyphoscoliosis, and reduced respiratory vital capacity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11079538" 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="Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P. &lt;strong&gt;A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.&lt;/strong&gt; Ann. Neurol. 51: 750-759, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12112081/&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;12112081&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10231&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="12112081">Ferreiro et al. (2002)</a> reported 3 affected members of a consanguineous Algerian family with CMYO1B manifest pathologically as central core disease transiently presenting as minicore myopathy. The 3 children presented in infancy with moderate weakness predominantly in axial muscles, pelvic girdle, and hands, joint hyperlaxity, and multiple minicores on skeletal muscle biopsy. Muscle biopsies from the 3 patients in adulthood demonstrated typical central core disease with rods; no cores were found in the healthy parents. Genetic analysis identified a homozygous mutation in the RYR1 gene (P3527S; <a href="/entry/180901#0021">180901.0021</a>). The family represented the first variant of central core disease with genetically proven recessive inheritance and transient presentation as minicore myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" 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>During an international workshop on multiminicore disease, <a href="#6" class="mim-tip-reference" title="Ferreiro, A., Fardeau, M. &lt;strong&gt;80th ENMC International Workshop on Multi-minicore Disease: 1st International MmD Workshop 12-13th May, 2000, Soestduinen, The Netherlands.&lt;/strong&gt; Neuromusc. Disord. 12: 60-68, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11731287/&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;11731287&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(01)00237-1&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="11731287">Ferreiro and Fardeau (2002)</a> reported 4 patients with external ophthalmoplegia of variable severity in addition to a generalized muscle involvement similar to the classic form of the disease. In this group, facial weakness, especially in the lower face, was severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731287" 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="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. &lt;strong&gt;Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.&lt;/strong&gt; Neurology 59: 284-287, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12136074/&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;12136074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.59.2.284&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="12136074">Jungbluth et al. (2002)</a> reported a 19-year-old girl, born of consanguineous parents, with CMYO1B manifest as central core disease on muscle biopsy. She presented at 4 years of age with moderate proximal weakness and mild scoliosis. She had weakness of the hip girdle, scoliosis, lumbar lordosis, and Achilles tendon contractures. Facial weakness was not noted. Skeletal muscle biopsy showed variability in fiber size, increased internal nuclei, a few rodlike structures, and multiple minicores and cores. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12136074" 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="#18" class="mim-tip-reference" title="Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J. &lt;strong&gt;A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.&lt;/strong&gt; Hum. Molec. Genet. 12: 1171-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12719381/&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;12719381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddg121&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="12719381">Monnier et al. (2003)</a> reported a 17-year-old Tunisian boy, born of consanguineous parents, with CMYO1B with cores and multiminicores on skeletal muscle biopsy. He had neonatal hypotonia, delayed motor development with walking at age 3 years, generalized muscle weakness and amyotrophy with loss of ambulation at 12 years of age, respiratory insufficiency, scoliosis, facial dysmorphism, thorax deformity, and ocular paresis. Serum creatine kinase was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719381" 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="#10" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. &lt;strong&gt;Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.&lt;/strong&gt; Neurology 65: 1930-1935, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16380615/&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;16380615&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000188870.37076.f2&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="16380615">Jungbluth et al. (2005)</a> reported 11 individuals from 5 families with CMYO1B manifest as multiminicore disease and external ophthalmoplegia. One of the families (family 2) had previously been reported by <a href="#21" class="mim-tip-reference" title="Swash, M., Schwartz, M. S. &lt;strong&gt;Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.&lt;/strong&gt; J. Neurol. Sci. 52: 1-10, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7299413/&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;7299413&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(81)90129-5&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="7299413">Swash and Schwartz (1981)</a>. All patients showed a fairly homogeneous clinical phenotype with onset of marked generalized hypotonia and weakness in the neonatal period or early infancy associated with feeding and respiratory difficulties. Two patients from 1 family exhibited prenatal symptoms with reduced fetal movements, polyhydramnios, and hydrops. Most showed delayed motor development and difficulty running in childhood; some patients also reported limited walking distances. Patients showed muscle wasting of the neck and shoulder girdle muscles; weakness was most pronounced in the axial and proximal versus distal muscle groups. External ophthalmoplegia predominantly affected upward and lateral gaze. Weakness was exacerbated by cold in 6 patients. Other features included ligamentous laxity, moderate scoliosis, and moderately impaired respiratory function. Serum creatine kinase was normal. Skeletal muscle biopsies showed nonspecific myopathic changes with variability in fiber size and increased central nucleation. Both type 1 and 2 fibers showed multiple and single core lesions that extended the full fiber diameter but often did not run for the entire longitudinal axis. There was focal loss of cross-striations and disorganization of the normal myofibrillar pattern. Leg muscle MRI of 5 patients showed relative sparing of the gracilis and gastrocnemii compared to the sartorius and soleus, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7299413+16380615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. &lt;strong&gt;Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.&lt;/strong&gt; Hum. Mutat. 29: 670-678, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18253926/&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;18253926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20696&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="18253926">Monnier et al. (2008)</a> reported 9 unrelated nonconsanguineous families in which affected individuals had a severe recessive form of congenital myopathy resulting from biallelic mutations in the RYR1 gene. The clinical presentation was variable: 4 probands showed very severe neonatal hypotonia associated with major respiratory problems, whereas 5 other probands had a comparably intermediate or moderate phenotype. All documented patients had involvement of extraocular muscles, and other variable features included facial diplegia, amyotrophy, scoliosis, kyphosis, and joint contractures. Skeletal biopsies showed core lesions whose size and aspect ranged from small to large diffuse cores that extended various distances in the longitudinal axis. One of the affected males with neonatal onset showed mild intermittent 3-methylglutaconic aciduria, a nonspecific finding. All patients were found to have at least 1 null RYR1 allele in compound heterozygosity with another pathogenic mutation (see, e.g., <a href="/entry/180901#0022">180901.0022</a> and <a href="/entry/180901#0032">180901.0032</a>), reflecting a critical functional decrease below 50% for the RYR1 protein. All heterozygous carriers were clinically unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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="#19" class="mim-tip-reference" title="Monnier, N., Laquerriere, A., Marret, S., Goldenberg, A., Marty, I., Nivoche, Y., Lunardi, J. &lt;strong&gt;First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia.&lt;/strong&gt; Neuromusc. Disord. 19: 680-684, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19734047/&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;19734047&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2009.07.007&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="19734047">Monnier et al. (2009)</a> reported a newborn male with global hypotonia, total immobility of all 4 limbs, a frog position, and feeding difficulties. He had generalized muscle weakness affecting axial and facial muscles, resulting in amimia and difficulty in opening his eyes. There was mild distal arthrogryposis but no craniofacial abnormalities. He had progressive respiratory failure and died at age 2 months. Skeletal muscle biopsy showed fiber size variability, with internal nuclei in about 10% of fibers, and strong type 1 fiber predominance, corresponding to congenital fiber-type disproportion. Although no definite cores were present, focal, ill-defined lack of oxidative activity was observed, which could be interpreted as atypical cores. Electron microscopy showed focal loss of myofibrils and small foci of sarcomeric disorganization with Z-band streaming. The diagnosis was atypical multiminicore myopathy. Molecular analysis identified compound heterozygosity for 2 mutations in the RYR1 gene, 1 of which was a large genomic deletion. Each unaffected parent was heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19734047" 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="#24" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. &lt;strong&gt;RYR1 mutations are a common cause of congenital myopathies with central nuclei.&lt;/strong&gt; Ann. Neurol. 68: 717-726, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20839240/&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;20839240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22119&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="20839240">Wilmshurst et al. (2010)</a> reported 17 patients from unrelated nonconsanguineous families with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy associated with RYR1 mutations. Twelve were from South Africa and 5 from European countries. All except 1 had onset from birth of neonatal hypotonia and weakness, and most had feeding difficulties. Decreased fetal movements were often reported. Clinical features included delayed motor development, achievement of sitting or walking only, extraocular muscle involvement, proximal muscle weakness, and frequent respiratory infections. Eight achieved sitting only, 8 achieved walking only, and 1 achieved neither. Bulbar involvement was also common, and 3 required gastrostomy. Three patients had scoliosis. All patients had a similar appearance, with myopathic facies, inverted V-shaped mouth, and ptosis. Skeletal muscle biopsies showed about 10% fibers with central nuclei and type 1 fiber predominance. There was also type 2 hypertrophy with fiber-type disproportion. None had core-like structures on early biopsies, but 2 of 3 patients with follow-up developed mild central or minicores. In addition, most biopsies showed central accumulation of oxidative abnormalities. Electron microscopic studies showed Z-line streaming, and 5 had apparent core-like structures. <a href="#24" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. &lt;strong&gt;RYR1 mutations are a common cause of congenital myopathies with central nuclei.&lt;/strong&gt; Ann. Neurol. 68: 717-726, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20839240/&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;20839240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22119&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="20839240">Wilmshurst et al. (2010)</a> noted the phenotypic overlap with the patients reported by <a href="#11" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Sewry, C. A., Robb, S., Treves, S., Bitoun, M., Guicheney, P., Buj-Bello, A., Bonnemann, C., Muntoni, F. &lt;strong&gt;Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.&lt;/strong&gt; Neuromusc. Disord. 17: 338-345, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17376685/&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;17376685&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2007.01.016&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="17376685">Jungbluth et al. (2007)</a> and <a href="#20" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. &lt;strong&gt;Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.&lt;/strong&gt; Hum. Mutat. 29: 670-678, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18253926/&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;18253926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20696&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="18253926">Monnier et al. (2008)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17376685+20839240+18253926" 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="Clarke, N. F., Waddell, L. B., Cooper, S. T., Perry, M., Smith, R. L. L., Kornberg, A. J., Muntoni, F., Lillis, S., Straub, V., Bushby, K., Guglieri, M., King, M. D., Farrell, M. A., Marty, I., Lunardi, J., Monnier, N., North, K. N. &lt;strong&gt;Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Hum. Mutat. 31: E1544-E1550, 2010. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20583297/&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;20583297&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.21278&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="20583297">Clarke et al. (2010)</a> identified compound heterozygous RYR1 mutations in 5 affected members of 4 families with a congenital myopathy characterized by congenital fiber-type disproportion (CFTD) on muscle biopsy. All patients presented at birth or in early childhood with severe muscle weakness and variable but generalized features of myopathy, including myopathic facies, ophthalmoplegia, high-arched palate, and respiratory insufficiency. Patient 1 had generalized hypotonia from birth, delayed motor development, muscle wasting, ophthalmoplegia, and facial weakness. He required nocturnal CPAP and gastrostomy tube; he died of respiratory failure at 3 years of age. Patient 2 had severe hypotonia and respiratory insufficiency from birth, frog-leg posture, poor antigravity movements, external ophthalmoplegia, ptosis, and weak cry. He was intubated at 26 days of life, but died at age 1 month following extubation. Serum creatine kinase was normal. Patient 3 was a 29-year-old man with generalized hypotonia from birth, poor feeding, delayed walking, and inability to run. He was thin with generalized muscle wasting and showed a long thin face, ptosis, ophthalmoplegia, strabismus, facial weakness, high-arched palate, and reduced mouth opening. Other features included scoliosis, Achilles tendon contractures, hip flexion contractures, and decreased forced vital capacity. Serum creatine kinase was normal. Patients 4 and 5 were sibs, aged 18 and 12 years, who presented in infancy or early childhood with difficulty walking and running due to proximal muscle weakness of the lower limbs. Other variable features included generalized muscle hypotrophy, positive Gowers sign, mild facial weakness with ptosis, mild scapular winging, and mild scoliosis. Neither had ophthalmoplegia or contractures, and serum creatine kinase was normal. MRI from patient 4 at age 12 years showed involvement of the gluteus maximus, vastus lateralis, adductor magnus, and soleus muscles, with sparing of the rectus femoris, semitendinosus, gracilis, tibialis anterior, and gastrocnemius muscles. Skeletal muscle biopsy in all patients was consistent with a pathologic diagnosis of CFTD with type 1 fiber hypotrophy relative to type 2 fibers, and without core or rod structures. Additional pathologic features included internalized nuclei and myofibrillar disarray. All patients carried 1 null RYR1 mutation and 1 missense mutation. None of the parents were clinically unaffected, except for 1 mother who had unilateral ptosis. There was no family history of malignant hyperthermia in these individuals, although the authors noted that since heterozygous RYR1 missense mutations in particular may confer susceptibility, standard malignant hyperthermia precautions should be taken during anesthesia, and in vitro contractility tests conducted, in patients with autosomal recessive CFTD. <a href="#3" class="mim-tip-reference" title="Clarke, N. F., Waddell, L. B., Cooper, S. T., Perry, M., Smith, R. L. L., Kornberg, A. J., Muntoni, F., Lillis, S., Straub, V., Bushby, K., Guglieri, M., King, M. D., Farrell, M. A., Marty, I., Lunardi, J., Monnier, N., North, K. N. &lt;strong&gt;Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Hum. Mutat. 31: E1544-E1550, 2010. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20583297/&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;20583297&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.21278&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="20583297">Clarke et al. (2010)</a> concluded that RYR1 mutations are a relatively common cause of congenital myopathy with CFTD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583297" 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="#13" class="mim-tip-reference" title="Kondo, E., Nishimura, T., Kosho, T., Inaba, Y., Mitsuhashi, S., Ishida, T., Baba, A., Koike, K., Nishino, I., Nonaka, I., Furukawa, T., Saito, K. &lt;strong&gt;Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia (sic) identified through massively parallel sequencing.&lt;/strong&gt; Am. J. Med. Genet. 158A: 772-778, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22407809/&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;22407809&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.35243&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="22407809">Kondo et al. (2012)</a> reported a Japanese male infant with severe congenital myopathy associated with compound heterozygous mutations in the RYR1 gene. The fetal period was complicated by nuchal translucency, fetal akinesia, and polyhydramnios. After birth, he showed generalized hypotonia, cyanosis, and bradycardia, necessitating intubation. He was noted to have a narrow face with facial muscle weakness, high-arched palate, ophthalmoplegia, and frog-leg posturing. Other features included micropenis, hypoplastic scrotum, and cryptorchidism. Although he had severe growth retardation in infancy, he later caught up to normal parameters. However, he had no ocular or swallowing movement. At age 1 year 9 months he showed an expressive face and some active limb movement, but he was mechanically ventilated and could not sit or speak. He showed some social development. Muscle biopsy showed cytoplasmic nemaline bodies and very small type 1 fibers, which were the predominant fiber type (71%). Central cores or minicores were not observed. The RYR1 mutations were identified by massively parallel sequencing and confirmed by Sanger sequencing; each unaffected parent was heterozygous for 1 of the mutations. <a href="#13" class="mim-tip-reference" title="Kondo, E., Nishimura, T., Kosho, T., Inaba, Y., Mitsuhashi, S., Ishida, T., Baba, A., Koike, K., Nishino, I., Nonaka, I., Furukawa, T., Saito, K. &lt;strong&gt;Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia (sic) identified through massively parallel sequencing.&lt;/strong&gt; Am. J. Med. Genet. 158A: 772-778, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22407809/&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;22407809&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.35243&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="22407809">Kondo et al. (2012)</a> commented that RYR1 mutations are usually not associated with the pathologic finding of nemaline rods, but that congenital myopathies can be heterogeneous in presentation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22407809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. &lt;strong&gt;Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.&lt;/strong&gt; Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22473935/&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;22473935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22056&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="22473935">Klein et al. (2012)</a> described 46 patients from 36 families with a congenital myopathy associated with biallelic RYR1 mutations, consistent with autosomal recessive inheritance. All patients with recessive mutations presented within the first 10 years of life, most at birth or prenatally. All had proximal weakness, some had distal weakness, and most had axial and facial weakness. More variable features included feeding difficulties and extraocular muscle involvement. Skeletal muscle biopsies tended to show type 1 fiber predominance or uniformity and core-like lesions; a few showed minicores. <a href="#12" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. &lt;strong&gt;Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.&lt;/strong&gt; Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22473935/&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;22473935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22056&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="22473935">Klein et al. (2012)</a> concluded that biallelic RYR1 mutations are at least as frequent as heterozygous mutations, and that there is marked variability in the clinical and pathologic features of RYR1-associated myopathies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bharucha-Goebel, D. X., Santi, M., Medne, L., Zukosky, K., Dastgir, J., Shieh, P. B., Winder, T., Tennekoon, G., Finkel, R. S., Dowling, J. J., Monnier, N., Bonnemann, C. G. &lt;strong&gt;Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.&lt;/strong&gt; Neurology 80: 1584-1589, 2013. Note: Erratum: Neurology 80: 2081 only, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23553484/&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;23553484&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=23553484[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.0b013e3182900380&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="23553484">Bharucha-Goebel et al. (2013)</a> reported 7 patients with severe CMYO1B due to recessive mutations in the RYR1 gene. Most had symptoms noted in utero, including decreased fetal movements, polyhydramnios, and intrauterine growth restriction. Variable features present at birth included hypotonia, feeding difficulties, arthrogryposis, hip dislocation, and respiratory insufficiency. Other variable features included kyphoscoliosis, cleft palate, rigid spine, and ophthalmoparesis. All patients had delayed motor milestones, but none showed evidence of intellectual impairment. Skeletal muscle biopsies were highly variable, showing fibrosis, small fibers, nonspecific myopathic changes, and a predominance of type 1 fibers, with or without ill-defined cores. Imaging tended to show sparing of the rectus femoris muscle. There were no genotype/phenotype correlations, and functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23553484" 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>Lethal Fetal Akinesia Phenotype</em></strong></p><p>
<a href="#17" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. &lt;strong&gt;Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.&lt;/strong&gt; Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25476234/&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;25476234&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0&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="25476234">McKie et al. (2014)</a> reported 3 unrelated consanguineous families with recurrent fetal akinesia resulting in termination of pregnancy or lethality in utero. The families were of Dutch, Pakistani, and Palestinian descent, respectively. Prenatal ultrasounds showed fetal akinesia, joint contractures, and increased nuchal translucency. Postmortem examination showed arthrogryposis, lung hypoplasia, cystic hygroma, and often clubfoot. Some affected fetuses had pterygia and/or dysmorphic facial features, such as hypertelorism, downslanting palpebral fissures, low-set ears, and cleft palate. Intrauterine growth was not restricted. Skeletal muscle biopsies of 2 affected sibs showed fiber loss, increased fiber size variability, increased endomysial spacing with fibrosis, and tendency toward hypotrophy of type 1 fibers. Ultrastructural examination showed muscle fiber hypotrophy with myofibrillar disarray and Z-disc loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" 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="#16" class="mim-tip-reference" title="Matthews, E., Neuwirth, C., Jaffer, F., Scalco, R. S., Fialho, D., Parton, M., Rayan, D. R., Suetterlin, K., Sud, R., Spiegel, R., Mein, R., Houlden, H., Schaefer, A., Healy, E., Palace, J., Quinlivan, R., Treves, S., Holton, J. L., Jungbluth, H., Hanna, M. G. &lt;strong&gt;Atypical periodic paralysis and myalgia: a novel RYR1 phenotype.&lt;/strong&gt; Neurology 90: e412-e418, 2018. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29298851/&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;29298851&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29298851[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.0000000000004894&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="29298851">Matthews et al. (2018)</a> reported 2 unrelated patients (cases 1 and 2) with periodic paralysis associated with compound heterozygous variants in the RYR1 gene. Case 1 was a 54-year-old man with a history of congenital myopathy since infancy who developed periodic paralysis at age 34 years. He had a waddling gait, long thin face, high-arched palate, lordosis, decreased reflexes, and ophthalmoplegia. Skeletal muscle biopsy showed some core-like structures. The McManis test for periodic paralysis was positive. Case 2 was a 42-year-old Swiss woman with a history of intermittent muscle weakness since age 23. She did not have features of a myopathy, EMG and muscle biopsy were normal, and the McManis test was negative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29298851" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of CMYO1B in the family reported by <a href="#18" class="mim-tip-reference" title="Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J. &lt;strong&gt;A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.&lt;/strong&gt; Hum. Molec. Genet. 12: 1171-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12719381/&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;12719381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddg121&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="12719381">Monnier et al. (2003)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719381" 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>Cases of congenital myopathy with cores consistent with autosomal recessive inheritance have been reported (<a href="#15" class="mim-tip-reference" title="Manzur, A. Y., Sewry, C. A., Ziprin, J., Dubowitz, V., Muntoni, F. &lt;strong&gt;A severe clinical and pathological variant of central core disease with possible autosomal recessive inheritance.&lt;/strong&gt; Neuromusc. Disord. 8: 467-473, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9829276/&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;9829276&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-8966(98)00064-9&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="9829276">Manzur et al., 1998</a>, <a href="#7" class="mim-tip-reference" title="Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P. &lt;strong&gt;A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.&lt;/strong&gt; Ann. Neurol. 51: 750-759, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12112081/&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;12112081&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10231&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="12112081">Ferreiro et al., 2002</a>, <a href="#8" class="mim-tip-reference" title="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. &lt;strong&gt;Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.&lt;/strong&gt; Neurology 59: 284-287, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12136074/&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;12136074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.59.2.284&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="12136074">Jungbluth et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12136074+12112081+9829276" 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="#25" class="mim-tip-reference" title="Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F. &lt;strong&gt;Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.&lt;/strong&gt; Am. J. Hum. Genet. 79: 859-868, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17033962/&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;17033962&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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/10.1086/508500&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="17033962">Zhou et al. (2006)</a> presented evidence that the RYR1 gene undergoes polymorphic, tissue-specific, and developmentally regulated allele silencing and that this can unveil recessive mutations in patients with core myopathies. Their data also suggested that imprinting is a likely mechanism for this phenomenon and that similar mechanisms can play a role in human phenotypic heterogeneity and in irregularities of inheritance patterns. <a href="#12" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. &lt;strong&gt;Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.&lt;/strong&gt; Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22473935/&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;22473935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22056&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="22473935">Klein et al. (2012)</a> found that some of the patients reported by <a href="#25" class="mim-tip-reference" title="Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F. &lt;strong&gt;Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.&lt;/strong&gt; Am. J. Hum. Genet. 79: 859-868, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17033962/&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;17033962&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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/10.1086/508500&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="17033962">Zhou et al. (2006)</a> with apparent mutations expressed monoallelically in the skeletal muscle were found to have another stop RYR1 mutation, resulting in nonsense-mediated mRNA decay and lack of expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17033962+22473935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#24" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. &lt;strong&gt;RYR1 mutations are a common cause of congenital myopathies with central nuclei.&lt;/strong&gt; Ann. Neurol. 68: 717-726, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20839240/&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;20839240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22119&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="20839240">Wilmshurst et al. (2010)</a> identified 3 recurrent RYR1 mutations in patients with CMYO1B from South Africa (<a href="/entry/180901#0035">180901.0035</a>-<a href="/entry/180901#0037">180901.0037</a>). Haplotype analysis suggested founder effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#26" class="mim-tip-reference" title="Zhou, H., Rokach, O., Feng, L., Munteanu, I., Mamchaoui, K., Wilmshurst, J. M., Sewry, C., Manzur, A. Y., Pillay, K., Mouly, V., Duchen, M., Jungbluth, H., Treves, S., Muntoni, F. &lt;strong&gt;RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling.&lt;/strong&gt; Hum. Mutat. 34: 986-996, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23553787/&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;23553787&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22326&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="23553787">Zhou et al. (2013)</a> found that levels of mutant RYR1 transcripts and protein were decreased in skeletal muscle from patients with recessive RYR1 mutations. Although mRNA levels of CACNA1S (<a href="/entry/114208">114208</a>), the alpha subunit of the dihydropyridine receptor (DHPR) were normal, there were decreased protein levels of DHPR in patient muscle, as well as disruption of DHPR-RYR1 colocalization in skeletal muscle. Human myoblasts transfected with RYR1 siRNA confirmed that knockdown of RYR1 downregulates not only the DHPR, but also the expression of other proteins involved in excitation-contraction (EC) coupling. These changes were also paralleled by the upregulation of all 3 inositol-1,4,5-triphosphate receptors (ITPR1, <a href="/entry/147265">147265</a>; ITPR2, <a href="/entry/600144">600144</a>; ITPR3, <a href="/entry/147267">147267</a>). However, upregulation of the ITPR calcium channels did not compensate for the lack of RYR1-mediated calcium release. The results suggested that RYR1 deficiency can cause EC uncoupling and alter the expression pattern of several proteins involved in calcium homeostasis, which may influence the manifestation of these diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23553787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a consanguineous Algerian family with CMYO1B, <a href="#7" class="mim-tip-reference" title="Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P. &lt;strong&gt;A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.&lt;/strong&gt; Ann. Neurol. 51: 750-759, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12112081/&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;12112081&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10231&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="12112081">Ferreiro et al. (2002)</a> identified a homozygous missense mutation in the RYR1 gene (P3527S; <a href="/entry/180901#0021">180901.0021</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 19-year-old girl, born of consanguineous parents (family 1), with CMYO1B, <a href="#8" class="mim-tip-reference" title="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. &lt;strong&gt;Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.&lt;/strong&gt; Neurology 59: 284-287, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12136074/&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;12136074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.59.2.284&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="12136074">Jungbluth et al. (2002)</a> identified a homozygous missense mutation in the RYR1 gene (V4849I; <a href="/entry/180901#0022">180901.0022</a>). In a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, <a href="#14" class="mim-tip-reference" title="Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M. &lt;strong&gt;Central core disease due to recessive mutations in RYR1 gene: is it more common than described?&lt;/strong&gt; Muscle Nerve 35: 670-674, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17226826/&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;17226826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/mus.20715&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="17226826">Kossugue et al. (2007)</a> identified a homozygous V4849I substitution in the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12136074+17226826" 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="#18" class="mim-tip-reference" title="Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J. &lt;strong&gt;A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.&lt;/strong&gt; Hum. Molec. Genet. 12: 1171-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12719381/&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;12719381&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddg121&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="12719381">Monnier et al. (2003)</a> and <a href="#10" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. &lt;strong&gt;Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.&lt;/strong&gt; Neurology 65: 1930-1935, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16380615/&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;16380615&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000188870.37076.f2&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="16380615">Jungbluth et al. (2005)</a> identified biallelic mutations in the RYR1 gene (see, e.g., <a href="/entry/180901#0025">180901.0025</a>-<a href="/entry/180901#0029">180901.0029</a>) in patients with CMYO1B manifest as minicore myopathy with external ophthalmoplegia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16380615+12719381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. &lt;strong&gt;Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.&lt;/strong&gt; Hum. Mutat. 29: 670-678, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18253926/&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;18253926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20696&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="18253926">Monnier et al. (2008)</a> reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (<a href="/entry/180901#0032">180901.0032</a>). <a href="#20" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. &lt;strong&gt;Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.&lt;/strong&gt; Hum. Mutat. 29: 670-678, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18253926/&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;18253926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.20696&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="18253926">Monnier et al. (2008)</a> postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 17 unrelated patients with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy (CNM), <a href="#24" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. &lt;strong&gt;RYR1 mutations are a common cause of congenital myopathies with central nuclei.&lt;/strong&gt; Ann. Neurol. 68: 717-726, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20839240/&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;20839240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.22119&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="20839240">Wilmshurst et al. (2010)</a> identified mutations in the RYR1 gene (see, e.g., <a href="/entry/180901#0035">180901.0035</a>-<a href="/entry/180901#0037">180901.0037</a>). Compound heterozygosity for a nonsense and missense mutation was found in all except 3 patients, in whom a second pathogenic allele could not be found. Twelve of the patients were from South Africa, and haplotype analysis suggested founder effects for some of the mutant alleles. The 17 patients were ascertained from a larger group of 24 patients with a diagnosis of CNM, indicating that RYR1 mutations can account for this subtype of myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected fetuses from 3 families with CMYO1B manifest as fetal akinesia deformation/lethal pterygium syndrome, <a href="#17" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. &lt;strong&gt;Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.&lt;/strong&gt; Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25476234/&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;25476234&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0&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="25476234">McKie et al. (2014)</a> identified 3 different homozygous nonsense or intragenic deletion mutations in the RYR1 gene (<a href="/entry/180901#0039">180901.0039</a>-<a href="/entry/180901#0041">180901.0041</a>). <a href="#17" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. &lt;strong&gt;Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.&lt;/strong&gt; Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25476234/&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;25476234&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0&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="25476234">McKie et al. (2014)</a> suggested that RYR1 mutation analysis should be performed in cases with severe early lethal fetal akinesia even in the absence of specific histopathologic indicators of RYR1-related disease. The patients were ascertained from a cohort of 36 families with the same phenotype; RYR1 mutations were found in 8.3%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The involvement of RYR1 mutations in a congenital myopathy is supported by the findings of <a href="#22" class="mim-tip-reference" title="Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T. &lt;strong&gt;Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.&lt;/strong&gt; Nature 369: 556-559, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7515481/&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;7515481&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/369556a0&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="7515481">Takeshima et al. (1994)</a>. Mice homozygous for a targeted mutation in the skeletal muscle ryanodine receptor gene died perinatally with gross abnormalities of skeletal muscle. The contractile response to electrical stimulation under physiologic conditions was totally abolished in the mutant muscle, although ryanodine receptors other than the skeletal-muscle type seemed to exist because the response to caffeine was retained. <a href="#22" class="mim-tip-reference" title="Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T. &lt;strong&gt;Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.&lt;/strong&gt; Nature 369: 556-559, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7515481/&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;7515481&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/369556a0&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="7515481">Takeshima et al. (1994)</a> interpreted the results as indicating that the skeletal muscle ryanodine receptor is essential for both muscular maturation and excitation-contraction (EC) coupling, and that the function of the skeletal muscle receptor during EC coupling cannot be substituted by other subtypes of the receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7515481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Bethlem1978" class="mim-anchor"></a>
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Bethlem, J., Arts, W. F., Dingemans, K. P.
<strong>Common origin of rods, cores, miniature cores and focal loss of cross striations.</strong>
Arch. Neurol. 35: 555-566, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/687182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">687182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=687182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.1978.00500330003002" target="_blank">Full Text</a>]
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<a id="Bharucha-Goebel2013" class="mim-anchor"></a>
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Bharucha-Goebel, D. X., Santi, M., Medne, L., Zukosky, K., Dastgir, J., Shieh, P. B., Winder, T., Tennekoon, G., Finkel, R. S., Dowling, J. J., Monnier, N., Bonnemann, C. G.
<strong>Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.</strong>
Neurology 80: 1584-1589, 2013. Note: Erratum: Neurology 80: 2081 only, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23553484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23553484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23553484[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=23553484" 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.0b013e3182900380" target="_blank">Full Text</a>]
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<a id="Clarke2010" class="mim-anchor"></a>
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Clarke, N. F., Waddell, L. B., Cooper, S. T., Perry, M., Smith, R. L. L., Kornberg, A. J., Muntoni, F., Lillis, S., Straub, V., Bushby, K., Guglieri, M., King, M. D., Farrell, M. A., Marty, I., Lunardi, J., Monnier, N., North, K. N.
<strong>Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.</strong>
Hum. Mutat. 31: E1544-E1550, 2010. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583297</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583297" 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/humu.21278" target="_blank">Full Text</a>]
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<a id="Engel1971" class="mim-anchor"></a>
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Engel, A. G., Gomez, M. R., Groover, R. V.
<strong>Multicore disease: a recently recognized congenital myopathy associated with multifocal degeneration of muscle fibres.</strong>
Mayo Clin. Proc. 46: 666-681, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5115748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5115748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5115748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Ferreiro2000" class="mim-anchor"></a>
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Ferreiro, A., Estournet, B., Chateau, D., Romero, N. B., Laroche, C., Odent, S., Toutain, A., Cabello, A., Fontan, D., dos Santos, H. G., Haenggeli, C.-A., Bertini, E., Urtizberea, J.-A., Guicheney, P., Fardeau, M.
<strong>Multi-minicore disease-searching for boundaries: phenotype analysis of 38 cases.</strong>
Ann. Neurol. 48: 745-757, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11079538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11079538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11079538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="Ferreiro2002" class="mim-anchor"></a>
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Ferreiro, A., Fardeau, M.
<strong>80th ENMC International Workshop on Multi-minicore Disease: 1st International MmD Workshop 12-13th May, 2000, Soestduinen, The Netherlands.</strong>
Neuromusc. Disord. 12: 60-68, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11731287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11731287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731287" 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/s0960-8966(01)00237-1" target="_blank">Full Text</a>]
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<a id="Ferreiro2002" class="mim-anchor"></a>
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Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P.
<strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong>
Ann. Neurol. 51: 750-759, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" 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/ana.10231" target="_blank">Full Text</a>]
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<a id="Jungbluth2002" class="mim-anchor"></a>
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Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F.
<strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong>
Neurology 59: 284-287, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12136074" 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.59.2.284" target="_blank">Full Text</a>]
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<a id="Jungbluth2000" class="mim-anchor"></a>
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Jungbluth, H., Sewry, C., Brown, S. C., Manzur, A. Y., Mercuri, E., Bushby, K., Rowe, P., Johnson, M. A., Hughes, I., Kelsey, A., Dubowitz, V., Muntoni, F.
<strong>Minicore myopathy in children: a clinical and histopathological study of 19 cases.</strong>
Neuromusc. Disord. 10: 264-273, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10838253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10838253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10838253" 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/s0960-8966(99)00125-x" target="_blank">Full Text</a>]
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<a id="Jungbluth2005" class="mim-anchor"></a>
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Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F.
<strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong>
Neurology 65: 1930-1935, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380615" 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.0000188870.37076.f2" target="_blank">Full Text</a>]
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<a id="Jungbluth2007" class="mim-anchor"></a>
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Jungbluth, H., Zhou, H., Sewry, C. A., Robb, S., Treves, S., Bitoun, M., Guicheney, P., Buj-Bello, A., Bonnemann, C., Muntoni, F.
<strong>Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.</strong>
Neuromusc. Disord. 17: 338-345, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17376685/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17376685</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17376685" 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.nmd.2007.01.016" target="_blank">Full Text</a>]
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<a id="Klein2012" class="mim-anchor"></a>
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Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others.
<strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong>
Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" 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/humu.22056" target="_blank">Full Text</a>]
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<a id="Kondo2012" class="mim-anchor"></a>
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Kondo, E., Nishimura, T., Kosho, T., Inaba, Y., Mitsuhashi, S., Ishida, T., Baba, A., Koike, K., Nishino, I., Nonaka, I., Furukawa, T., Saito, K.
<strong>Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia (sic) identified through massively parallel sequencing.</strong>
Am. J. Med. Genet. 158A: 772-778, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22407809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22407809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22407809" 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.35243" target="_blank">Full Text</a>]
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</li>
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<a id="14" class="mim-anchor"></a>
<a id="Kossugue2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M.
<strong>Central core disease due to recessive mutations in RYR1 gene: is it more common than described?</strong>
Muscle Nerve 35: 670-674, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17226826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17226826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17226826" 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/mus.20715" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Manzur1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Manzur, A. Y., Sewry, C. A., Ziprin, J., Dubowitz, V., Muntoni, F.
<strong>A severe clinical and pathological variant of central core disease with possible autosomal recessive inheritance.</strong>
Neuromusc. Disord. 8: 467-473, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9829276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9829276</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9829276" 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/s0960-8966(98)00064-9" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Matthews2018" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matthews, E., Neuwirth, C., Jaffer, F., Scalco, R. S., Fialho, D., Parton, M., Rayan, D. R., Suetterlin, K., Sud, R., Spiegel, R., Mein, R., Houlden, H., Schaefer, A., Healy, E., Palace, J., Quinlivan, R., Treves, S., Holton, J. L., Jungbluth, H., Hanna, M. G.
<strong>Atypical periodic paralysis and myalgia: a novel RYR1 phenotype.</strong>
Neurology 90: e412-e418, 2018. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29298851/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29298851</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29298851[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=29298851" 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.0000000000004894" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="McKie2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R.
<strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong>
Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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=25476234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1186/s40478-014-0148-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Monnier2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J.
<strong>A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.</strong>
Hum. Molec. Genet. 12: 1171-1178, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddg121" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Monnier2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Monnier, N., Laquerriere, A., Marret, S., Goldenberg, A., Marty, I., Nivoche, Y., Lunardi, J.
<strong>First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia.</strong>
Neuromusc. Disord. 19: 680-684, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19734047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19734047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19734047" 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.nmd.2009.07.007" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Monnier2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J.
<strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong>
Hum. Mutat. 29: 670-678, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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/humu.20696" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Swash1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Swash, M., Schwartz, M. S.
<strong>Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.</strong>
J. Neurol. Sci. 52: 1-10, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7299413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7299413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7299413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-510x(81)90129-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Takeshima1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T.
<strong>Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.</strong>
Nature 369: 556-559, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7515481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7515481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7515481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/369556a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Van Wijngaarden1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Van Wijngaarden, G. K., Bethlem, J., Dingemans, K. P., Coers, C., Telerman-Toppet, N., Gerard, J. M.
<strong>Familial focal loss of cross striations.</strong>
J. Neurol. 216: 163-172, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/72134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">72134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=72134" 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/BF00313617" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Wilmshurst2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others.
<strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong>
Ann. Neurol. 68: 717-726, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" 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/ana.22119" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Zhou2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F.
<strong>Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.</strong>
Am. J. Hum. Genet. 79: 859-868, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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=17033962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/508500" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Zhou2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zhou, H., Rokach, O., Feng, L., Munteanu, I., Mamchaoui, K., Wilmshurst, J. M., Sewry, C., Manzur, A. Y., Pillay, K., Mouly, V., Duchen, M., Jungbluth, H., Treves, S., Muntoni, F.
<strong>RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling.</strong>
Hum. Mutat. 34: 986-996, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23553787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23553787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23553787" 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/humu.22326" target="_blank">Full Text</a>]
</p>
</div>
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<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 02/24/2023
</span>
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</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 5/20/2015<br>Cassandra L. Kniffin - updated : 12/2/2014<br>Cassandra L. Kniffin - updated : 7/24/2013<br>Cassandra L. Kniffin - updated : 1/14/2013<br>Cassandra L. Kniffin - updated : 2/23/2011<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 8/26/2008<br>Cassandra L. Kniffin - updated : 4/6/2006<br>Victor A. McKusick - updated : 3/28/2005<br>Cassandra L. Kniffin - reorganized : 2/20/2003<br>Cassandra L. Kniffin - updated : 2/11/2003<br>Victor A. McKusick - updated : 9/17/2002<br>Orest Hurko - updated : 3/23/1999
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<div>
<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/4/1986
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<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 07/16/2024
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<div class="row collapse" id="mimCollapseEditHistory">
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
alopez : 11/15/2023<br>carol : 05/26/2023<br>alopez : 03/10/2023<br>alopez : 02/27/2023<br>ckniffin : 02/24/2023<br>carol : 02/20/2023<br>alopez : 12/03/2020<br>carol : 11/30/2020<br>alopez : 05/22/2015<br>mcolton : 5/21/2015<br>ckniffin : 5/20/2015<br>carol : 12/9/2014<br>mcolton : 12/8/2014<br>ckniffin : 12/2/2014<br>carol : 7/25/2013<br>tpirozzi : 7/25/2013<br>ckniffin : 7/24/2013<br>alopez : 1/22/2013<br>ckniffin : 1/14/2013<br>wwang : 3/10/2011<br>ckniffin : 2/23/2011<br>ckniffin : 3/23/2010<br>wwang : 11/17/2009<br>wwang : 11/17/2009<br>wwang : 11/16/2009<br>ckniffin : 10/27/2009<br>wwang : 9/19/2008<br>ckniffin : 8/26/2008<br>wwang : 4/12/2006<br>ckniffin : 4/6/2006<br>carol : 3/28/2005<br>carol : 3/28/2005<br>carol : 3/17/2005<br>carol : 2/20/2003<br>ckniffin : 2/11/2003<br>mgross : 11/8/2002<br>mgross : 11/7/2002<br>tkritzer : 9/17/2002<br>carol : 3/23/1999<br>mimman : 2/8/1996<br>carol : 1/25/1995<br>supermim : 3/17/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>marie : 3/25/1988<br>carol : 3/27/1987
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<h3>
<span class="mim-font">
<strong>#</strong> 255320
</span>
</h3>
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<h3>
<span class="mim-font">
CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE; CMYO1B
</span>
</h3>
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<div>
<br />
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<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MINICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA<br />
MINICORE MYOPATHY<br />
MULTICORE MYOPATHY<br />
MULTIMINICORE MYOPATHY<br />
MULTICORE MYOPATHY WITH EXTERNAL OPHTHALMOPLEGIA<br />
MULTIMINICORE DISEASE WITH EXTERNAL OPHTHALMOPLEGIA
</span>
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<br />
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<p>
<span class="mim-text-font">
<strong>ICD10CM:</strong> G71.29; &nbsp;
<strong>ORPHA:</strong> 598, 98905; &nbsp;
<strong>DO:</strong> 0080991; &nbsp;
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<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
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</h4>
<div>
<table class="table table-bordered table-condensed 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">
19q13.2
</span>
</td>
<td>
<span class="mim-font">
Congenital myopathy 1B, autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
255320
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
RYR1
</span>
</td>
<td>
<span class="mim-font">
180901
</span>
</td>
</tr>
</tbody>
</table>
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<div>
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<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that autosomal recessive congenital myopathy-1B (CMYO1B) is caused by homozygous or compound heterozygous mutation in the RYR1 gene (180901) on chromosome 19q13.</p><p>Heterozygous mutation in the RYR1 gene causes autosomal dominant CMYO1A (117000), which shows clinical overlap with CMYO1B, but is less severe.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Congenital myopathy-1B (CMYO1B) is an autosomal recessive disorder of skeletal muscle characterized by severe hypotonia and generalized muscle weakness apparent soon after birth or in early childhood with delayed motor development, generalized muscle weakness and atrophy, and difficulty walking or running. Affected individuals show proximal muscle weakness with axial and shoulder girdle involvement, external ophthalmoplegia, and bulbar weakness, often resulting in feeding difficulties and respiratory insufficiency. Orthopedic complications such as joint laxity, distal contractures, hip dislocation, cleft palate, and scoliosis are commonly observed. Serum creatine kinase is normal. The phenotype is variable in severity (Jungbluth et al., 2005; Bharucha-Goebel et al., 2013). Some patients show symptoms in utero, including reduced fetal movements, polyhydramnios, and intrauterine growth restriction. The most severely affected patients present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (McKie et al., 2014). Skeletal muscle biopsy of patients with recessive RYR1 mutations can show variable features, including multiminicores (Ferreiro and Fardeau, 2002), central cores (Jungbluth et al., 2002), congenital fiber-type disproportion (CFTD) (Monnier et al., 2009), and centronuclear myopathy (Wilmshurst et al., 2010). </p><p>For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000).</p>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Engel et al. (1971) first reported multiminicore myopathy in 2 affected sibs. The disorder was a congenital myopathy associated with multifocal degeneration of muscle fibers on pathologic examination. </p><p>Bethlem et al. (1978) noted external ophthalmoplegia in 2 sibs (family C, patients 7 and 8) in whom muscle biopsies showed both multicores and focal loss of cross-striations. The family was also reported by Van Wijngaarden et al. (1977). </p><p>Swash and Schwartz (1981) reported 2 brothers and a sister with a congenital myopathy characterized clinically by proximal weakness and external ophthalmoplegia and histologically by multicores and areas of focal loss of cross-striations in skeletal muscles. Both brothers showed highly arched palate. One brother, more severely affected than the other, developed respiratory failure in association with Mycoplasma pneumonia at age 14 years, and required mechanical ventilation for 3 days. Two other sisters and both parents were clinically normal. Swash and Schwartz (1981) noted the similarities to the phenotype described by Bethlem et al. (1978). Swash and Schwartz (1981) pointed out that previously reported patients in whom ophthalmoplegia was associated with core-like lesions all had focal loss of cross-striations as a prominent feature, with or without multicores (Engel et al., 1971; Van Wijngaarden et al., 1977; Bethlem et al., 1978), as in their patients. The authors regarded this disorder as a genetically distinct subtype of multicore disease. </p><p>Among 19 cases of minicore myopathy, Jungbluth et al. (2000) reported 2 with complete external ophthalmoplegia and a severe phenotype, including hypotonia and facial, axial, and proximal weakness. </p><p>Among 38 patients with histologically proven minicore myopathy, Ferreiro et al. (2000) reported 3 who had an antenatal-onset form with congenital generalized arthrogryposis, which the authors suggested was a distinct subtype of multiminicore disease. Other features included dolichocephaly, prominent nasal root, oblique palpebral fissures, high-arched palate, low-set ears, and short neck with mild pterygium colli. Two brothers also had a bell-shaped thorax, clinodactyly, bilateral cryptorchidism, and a single palmar crease. All 3 patients had moderate predominantly axial muscle weakness, early severe kyphosis or kyphoscoliosis, and reduced respiratory vital capacity. </p><p>Ferreiro et al. (2002) reported 3 affected members of a consanguineous Algerian family with CMYO1B manifest pathologically as central core disease transiently presenting as minicore myopathy. The 3 children presented in infancy with moderate weakness predominantly in axial muscles, pelvic girdle, and hands, joint hyperlaxity, and multiple minicores on skeletal muscle biopsy. Muscle biopsies from the 3 patients in adulthood demonstrated typical central core disease with rods; no cores were found in the healthy parents. Genetic analysis identified a homozygous mutation in the RYR1 gene (P3527S; 180901.0021). The family represented the first variant of central core disease with genetically proven recessive inheritance and transient presentation as minicore myopathy. </p><p>During an international workshop on multiminicore disease, Ferreiro and Fardeau (2002) reported 4 patients with external ophthalmoplegia of variable severity in addition to a generalized muscle involvement similar to the classic form of the disease. In this group, facial weakness, especially in the lower face, was severe. </p><p>Jungbluth et al. (2002) reported a 19-year-old girl, born of consanguineous parents, with CMYO1B manifest as central core disease on muscle biopsy. She presented at 4 years of age with moderate proximal weakness and mild scoliosis. She had weakness of the hip girdle, scoliosis, lumbar lordosis, and Achilles tendon contractures. Facial weakness was not noted. Skeletal muscle biopsy showed variability in fiber size, increased internal nuclei, a few rodlike structures, and multiple minicores and cores. </p><p>Monnier et al. (2003) reported a 17-year-old Tunisian boy, born of consanguineous parents, with CMYO1B with cores and multiminicores on skeletal muscle biopsy. He had neonatal hypotonia, delayed motor development with walking at age 3 years, generalized muscle weakness and amyotrophy with loss of ambulation at 12 years of age, respiratory insufficiency, scoliosis, facial dysmorphism, thorax deformity, and ocular paresis. Serum creatine kinase was normal. </p><p>Jungbluth et al. (2005) reported 11 individuals from 5 families with CMYO1B manifest as multiminicore disease and external ophthalmoplegia. One of the families (family 2) had previously been reported by Swash and Schwartz (1981). All patients showed a fairly homogeneous clinical phenotype with onset of marked generalized hypotonia and weakness in the neonatal period or early infancy associated with feeding and respiratory difficulties. Two patients from 1 family exhibited prenatal symptoms with reduced fetal movements, polyhydramnios, and hydrops. Most showed delayed motor development and difficulty running in childhood; some patients also reported limited walking distances. Patients showed muscle wasting of the neck and shoulder girdle muscles; weakness was most pronounced in the axial and proximal versus distal muscle groups. External ophthalmoplegia predominantly affected upward and lateral gaze. Weakness was exacerbated by cold in 6 patients. Other features included ligamentous laxity, moderate scoliosis, and moderately impaired respiratory function. Serum creatine kinase was normal. Skeletal muscle biopsies showed nonspecific myopathic changes with variability in fiber size and increased central nucleation. Both type 1 and 2 fibers showed multiple and single core lesions that extended the full fiber diameter but often did not run for the entire longitudinal axis. There was focal loss of cross-striations and disorganization of the normal myofibrillar pattern. Leg muscle MRI of 5 patients showed relative sparing of the gracilis and gastrocnemii compared to the sartorius and soleus, respectively. </p><p>Monnier et al. (2008) reported 9 unrelated nonconsanguineous families in which affected individuals had a severe recessive form of congenital myopathy resulting from biallelic mutations in the RYR1 gene. The clinical presentation was variable: 4 probands showed very severe neonatal hypotonia associated with major respiratory problems, whereas 5 other probands had a comparably intermediate or moderate phenotype. All documented patients had involvement of extraocular muscles, and other variable features included facial diplegia, amyotrophy, scoliosis, kyphosis, and joint contractures. Skeletal biopsies showed core lesions whose size and aspect ranged from small to large diffuse cores that extended various distances in the longitudinal axis. One of the affected males with neonatal onset showed mild intermittent 3-methylglutaconic aciduria, a nonspecific finding. All patients were found to have at least 1 null RYR1 allele in compound heterozygosity with another pathogenic mutation (see, e.g., 180901.0022 and 180901.0032), reflecting a critical functional decrease below 50% for the RYR1 protein. All heterozygous carriers were clinically unaffected. </p><p>Monnier et al. (2009) reported a newborn male with global hypotonia, total immobility of all 4 limbs, a frog position, and feeding difficulties. He had generalized muscle weakness affecting axial and facial muscles, resulting in amimia and difficulty in opening his eyes. There was mild distal arthrogryposis but no craniofacial abnormalities. He had progressive respiratory failure and died at age 2 months. Skeletal muscle biopsy showed fiber size variability, with internal nuclei in about 10% of fibers, and strong type 1 fiber predominance, corresponding to congenital fiber-type disproportion. Although no definite cores were present, focal, ill-defined lack of oxidative activity was observed, which could be interpreted as atypical cores. Electron microscopy showed focal loss of myofibrils and small foci of sarcomeric disorganization with Z-band streaming. The diagnosis was atypical multiminicore myopathy. Molecular analysis identified compound heterozygosity for 2 mutations in the RYR1 gene, 1 of which was a large genomic deletion. Each unaffected parent was heterozygous for 1 of the mutations. </p><p>Wilmshurst et al. (2010) reported 17 patients from unrelated nonconsanguineous families with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy associated with RYR1 mutations. Twelve were from South Africa and 5 from European countries. All except 1 had onset from birth of neonatal hypotonia and weakness, and most had feeding difficulties. Decreased fetal movements were often reported. Clinical features included delayed motor development, achievement of sitting or walking only, extraocular muscle involvement, proximal muscle weakness, and frequent respiratory infections. Eight achieved sitting only, 8 achieved walking only, and 1 achieved neither. Bulbar involvement was also common, and 3 required gastrostomy. Three patients had scoliosis. All patients had a similar appearance, with myopathic facies, inverted V-shaped mouth, and ptosis. Skeletal muscle biopsies showed about 10% fibers with central nuclei and type 1 fiber predominance. There was also type 2 hypertrophy with fiber-type disproportion. None had core-like structures on early biopsies, but 2 of 3 patients with follow-up developed mild central or minicores. In addition, most biopsies showed central accumulation of oxidative abnormalities. Electron microscopic studies showed Z-line streaming, and 5 had apparent core-like structures. Wilmshurst et al. (2010) noted the phenotypic overlap with the patients reported by Jungbluth et al. (2007) and Monnier et al. (2008). </p><p>Clarke et al. (2010) identified compound heterozygous RYR1 mutations in 5 affected members of 4 families with a congenital myopathy characterized by congenital fiber-type disproportion (CFTD) on muscle biopsy. All patients presented at birth or in early childhood with severe muscle weakness and variable but generalized features of myopathy, including myopathic facies, ophthalmoplegia, high-arched palate, and respiratory insufficiency. Patient 1 had generalized hypotonia from birth, delayed motor development, muscle wasting, ophthalmoplegia, and facial weakness. He required nocturnal CPAP and gastrostomy tube; he died of respiratory failure at 3 years of age. Patient 2 had severe hypotonia and respiratory insufficiency from birth, frog-leg posture, poor antigravity movements, external ophthalmoplegia, ptosis, and weak cry. He was intubated at 26 days of life, but died at age 1 month following extubation. Serum creatine kinase was normal. Patient 3 was a 29-year-old man with generalized hypotonia from birth, poor feeding, delayed walking, and inability to run. He was thin with generalized muscle wasting and showed a long thin face, ptosis, ophthalmoplegia, strabismus, facial weakness, high-arched palate, and reduced mouth opening. Other features included scoliosis, Achilles tendon contractures, hip flexion contractures, and decreased forced vital capacity. Serum creatine kinase was normal. Patients 4 and 5 were sibs, aged 18 and 12 years, who presented in infancy or early childhood with difficulty walking and running due to proximal muscle weakness of the lower limbs. Other variable features included generalized muscle hypotrophy, positive Gowers sign, mild facial weakness with ptosis, mild scapular winging, and mild scoliosis. Neither had ophthalmoplegia or contractures, and serum creatine kinase was normal. MRI from patient 4 at age 12 years showed involvement of the gluteus maximus, vastus lateralis, adductor magnus, and soleus muscles, with sparing of the rectus femoris, semitendinosus, gracilis, tibialis anterior, and gastrocnemius muscles. Skeletal muscle biopsy in all patients was consistent with a pathologic diagnosis of CFTD with type 1 fiber hypotrophy relative to type 2 fibers, and without core or rod structures. Additional pathologic features included internalized nuclei and myofibrillar disarray. All patients carried 1 null RYR1 mutation and 1 missense mutation. None of the parents were clinically unaffected, except for 1 mother who had unilateral ptosis. There was no family history of malignant hyperthermia in these individuals, although the authors noted that since heterozygous RYR1 missense mutations in particular may confer susceptibility, standard malignant hyperthermia precautions should be taken during anesthesia, and in vitro contractility tests conducted, in patients with autosomal recessive CFTD. Clarke et al. (2010) concluded that RYR1 mutations are a relatively common cause of congenital myopathy with CFTD. </p><p>Kondo et al. (2012) reported a Japanese male infant with severe congenital myopathy associated with compound heterozygous mutations in the RYR1 gene. The fetal period was complicated by nuchal translucency, fetal akinesia, and polyhydramnios. After birth, he showed generalized hypotonia, cyanosis, and bradycardia, necessitating intubation. He was noted to have a narrow face with facial muscle weakness, high-arched palate, ophthalmoplegia, and frog-leg posturing. Other features included micropenis, hypoplastic scrotum, and cryptorchidism. Although he had severe growth retardation in infancy, he later caught up to normal parameters. However, he had no ocular or swallowing movement. At age 1 year 9 months he showed an expressive face and some active limb movement, but he was mechanically ventilated and could not sit or speak. He showed some social development. Muscle biopsy showed cytoplasmic nemaline bodies and very small type 1 fibers, which were the predominant fiber type (71%). Central cores or minicores were not observed. The RYR1 mutations were identified by massively parallel sequencing and confirmed by Sanger sequencing; each unaffected parent was heterozygous for 1 of the mutations. Kondo et al. (2012) commented that RYR1 mutations are usually not associated with the pathologic finding of nemaline rods, but that congenital myopathies can be heterogeneous in presentation. </p><p>Klein et al. (2012) described 46 patients from 36 families with a congenital myopathy associated with biallelic RYR1 mutations, consistent with autosomal recessive inheritance. All patients with recessive mutations presented within the first 10 years of life, most at birth or prenatally. All had proximal weakness, some had distal weakness, and most had axial and facial weakness. More variable features included feeding difficulties and extraocular muscle involvement. Skeletal muscle biopsies tended to show type 1 fiber predominance or uniformity and core-like lesions; a few showed minicores. Klein et al. (2012) concluded that biallelic RYR1 mutations are at least as frequent as heterozygous mutations, and that there is marked variability in the clinical and pathologic features of RYR1-associated myopathies. </p><p>Bharucha-Goebel et al. (2013) reported 7 patients with severe CMYO1B due to recessive mutations in the RYR1 gene. Most had symptoms noted in utero, including decreased fetal movements, polyhydramnios, and intrauterine growth restriction. Variable features present at birth included hypotonia, feeding difficulties, arthrogryposis, hip dislocation, and respiratory insufficiency. Other variable features included kyphoscoliosis, cleft palate, rigid spine, and ophthalmoparesis. All patients had delayed motor milestones, but none showed evidence of intellectual impairment. Skeletal muscle biopsies were highly variable, showing fibrosis, small fibers, nonspecific myopathic changes, and a predominance of type 1 fibers, with or without ill-defined cores. Imaging tended to show sparing of the rectus femoris muscle. There were no genotype/phenotype correlations, and functional studies of the variants were not performed. </p><p><strong><em>Lethal Fetal Akinesia Phenotype</em></strong></p><p>
McKie et al. (2014) reported 3 unrelated consanguineous families with recurrent fetal akinesia resulting in termination of pregnancy or lethality in utero. The families were of Dutch, Pakistani, and Palestinian descent, respectively. Prenatal ultrasounds showed fetal akinesia, joint contractures, and increased nuchal translucency. Postmortem examination showed arthrogryposis, lung hypoplasia, cystic hygroma, and often clubfoot. Some affected fetuses had pterygia and/or dysmorphic facial features, such as hypertelorism, downslanting palpebral fissures, low-set ears, and cleft palate. Intrauterine growth was not restricted. Skeletal muscle biopsies of 2 affected sibs showed fiber loss, increased fiber size variability, increased endomysial spacing with fibrosis, and tendency toward hypotrophy of type 1 fibers. Ultrastructural examination showed muscle fiber hypotrophy with myofibrillar disarray and Z-disc loss. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Matthews et al. (2018) reported 2 unrelated patients (cases 1 and 2) with periodic paralysis associated with compound heterozygous variants in the RYR1 gene. Case 1 was a 54-year-old man with a history of congenital myopathy since infancy who developed periodic paralysis at age 34 years. He had a waddling gait, long thin face, high-arched palate, lordosis, decreased reflexes, and ophthalmoplegia. Skeletal muscle biopsy showed some core-like structures. The McManis test for periodic paralysis was positive. Case 2 was a 42-year-old Swiss woman with a history of intermittent muscle weakness since age 23. She did not have features of a myopathy, EMG and muscle biopsy were normal, and the McManis test was negative. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The transmission pattern of CMYO1B in the family reported by Monnier et al. (2003) was consistent with autosomal recessive inheritance. </p><p>Cases of congenital myopathy with cores consistent with autosomal recessive inheritance have been reported (Manzur et al., 1998, Ferreiro et al., 2002, Jungbluth et al., 2002). </p><p>Zhou et al. (2006) presented evidence that the RYR1 gene undergoes polymorphic, tissue-specific, and developmentally regulated allele silencing and that this can unveil recessive mutations in patients with core myopathies. Their data also suggested that imprinting is a likely mechanism for this phenomenon and that similar mechanisms can play a role in human phenotypic heterogeneity and in irregularities of inheritance patterns. Klein et al. (2012) found that some of the patients reported by Zhou et al. (2006) with apparent mutations expressed monoallelically in the skeletal muscle were found to have another stop RYR1 mutation, resulting in nonsense-mediated mRNA decay and lack of expression. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Wilmshurst et al. (2010) identified 3 recurrent RYR1 mutations in patients with CMYO1B from South Africa (180901.0035-180901.0037). Haplotype analysis suggested founder effects. </p>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Zhou et al. (2013) found that levels of mutant RYR1 transcripts and protein were decreased in skeletal muscle from patients with recessive RYR1 mutations. Although mRNA levels of CACNA1S (114208), the alpha subunit of the dihydropyridine receptor (DHPR) were normal, there were decreased protein levels of DHPR in patient muscle, as well as disruption of DHPR-RYR1 colocalization in skeletal muscle. Human myoblasts transfected with RYR1 siRNA confirmed that knockdown of RYR1 downregulates not only the DHPR, but also the expression of other proteins involved in excitation-contraction (EC) coupling. These changes were also paralleled by the upregulation of all 3 inositol-1,4,5-triphosphate receptors (ITPR1, 147265; ITPR2, 600144; ITPR3, 147267). However, upregulation of the ITPR calcium channels did not compensate for the lack of RYR1-mediated calcium release. The results suggested that RYR1 deficiency can cause EC uncoupling and alter the expression pattern of several proteins involved in calcium homeostasis, which may influence the manifestation of these diseases. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In affected members of a consanguineous Algerian family with CMYO1B, Ferreiro et al. (2002) identified a homozygous missense mutation in the RYR1 gene (P3527S; 180901.0021). </p><p>In a 19-year-old girl, born of consanguineous parents (family 1), with CMYO1B, Jungbluth et al. (2002) identified a homozygous missense mutation in the RYR1 gene (V4849I; 180901.0022). In a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, Kossugue et al. (2007) identified a homozygous V4849I substitution in the RYR1 gene. </p><p>Monnier et al. (2003) and Jungbluth et al. (2005) identified biallelic mutations in the RYR1 gene (see, e.g., 180901.0025-180901.0029) in patients with CMYO1B manifest as minicore myopathy with external ophthalmoplegia. </p><p>Monnier et al. (2008) reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (180901.0032). Monnier et al. (2008) postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. </p><p>In 17 unrelated patients with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy (CNM), Wilmshurst et al. (2010) identified mutations in the RYR1 gene (see, e.g., 180901.0035-180901.0037). Compound heterozygosity for a nonsense and missense mutation was found in all except 3 patients, in whom a second pathogenic allele could not be found. Twelve of the patients were from South Africa, and haplotype analysis suggested founder effects for some of the mutant alleles. The 17 patients were ascertained from a larger group of 24 patients with a diagnosis of CNM, indicating that RYR1 mutations can account for this subtype of myopathy. </p><p>In affected fetuses from 3 families with CMYO1B manifest as fetal akinesia deformation/lethal pterygium syndrome, McKie et al. (2014) identified 3 different homozygous nonsense or intragenic deletion mutations in the RYR1 gene (180901.0039-180901.0041). McKie et al. (2014) suggested that RYR1 mutation analysis should be performed in cases with severe early lethal fetal akinesia even in the absence of specific histopathologic indicators of RYR1-related disease. The patients were ascertained from a cohort of 36 families with the same phenotype; RYR1 mutations were found in 8.3%. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The involvement of RYR1 mutations in a congenital myopathy is supported by the findings of Takeshima et al. (1994). Mice homozygous for a targeted mutation in the skeletal muscle ryanodine receptor gene died perinatally with gross abnormalities of skeletal muscle. The contractile response to electrical stimulation under physiologic conditions was totally abolished in the mutant muscle, although ryanodine receptors other than the skeletal-muscle type seemed to exist because the response to caffeine was retained. Takeshima et al. (1994) interpreted the results as indicating that the skeletal muscle ryanodine receptor is essential for both muscular maturation and excitation-contraction (EC) coupling, and that the function of the skeletal muscle receptor during EC coupling cannot be substituted by other subtypes of the receptor. </p>
</span>
<div>
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</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Bethlem, J., Arts, W. F., Dingemans, K. P.
<strong>Common origin of rods, cores, miniature cores and focal loss of cross striations.</strong>
Arch. Neurol. 35: 555-566, 1978.
[PubMed: 687182]
[Full Text: https://doi.org/10.1001/archneur.1978.00500330003002]
</p>
</li>
<li>
<p class="mim-text-font">
Bharucha-Goebel, D. X., Santi, M., Medne, L., Zukosky, K., Dastgir, J., Shieh, P. B., Winder, T., Tennekoon, G., Finkel, R. S., Dowling, J. J., Monnier, N., Bonnemann, C. G.
<strong>Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.</strong>
Neurology 80: 1584-1589, 2013. Note: Erratum: Neurology 80: 2081 only, 2013.
[PubMed: 23553484]
[Full Text: https://doi.org/10.1212/WNL.0b013e3182900380]
</p>
</li>
<li>
<p class="mim-text-font">
Clarke, N. F., Waddell, L. B., Cooper, S. T., Perry, M., Smith, R. L. L., Kornberg, A. J., Muntoni, F., Lillis, S., Straub, V., Bushby, K., Guglieri, M., King, M. D., Farrell, M. A., Marty, I., Lunardi, J., Monnier, N., North, K. N.
<strong>Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.</strong>
Hum. Mutat. 31: E1544-E1550, 2010. Note: Electronic Article.
[PubMed: 20583297]
[Full Text: https://doi.org/10.1002/humu.21278]
</p>
</li>
<li>
<p class="mim-text-font">
Engel, A. G., Gomez, M. R., Groover, R. V.
<strong>Multicore disease: a recently recognized congenital myopathy associated with multifocal degeneration of muscle fibres.</strong>
Mayo Clin. Proc. 46: 666-681, 1971.
[PubMed: 5115748]
</p>
</li>
<li>
<p class="mim-text-font">
Ferreiro, A., Estournet, B., Chateau, D., Romero, N. B., Laroche, C., Odent, S., Toutain, A., Cabello, A., Fontan, D., dos Santos, H. G., Haenggeli, C.-A., Bertini, E., Urtizberea, J.-A., Guicheney, P., Fardeau, M.
<strong>Multi-minicore disease-searching for boundaries: phenotype analysis of 38 cases.</strong>
Ann. Neurol. 48: 745-757, 2000.
[PubMed: 11079538]
</p>
</li>
<li>
<p class="mim-text-font">
Ferreiro, A., Fardeau, M.
<strong>80th ENMC International Workshop on Multi-minicore Disease: 1st International MmD Workshop 12-13th May, 2000, Soestduinen, The Netherlands.</strong>
Neuromusc. Disord. 12: 60-68, 2002.
[PubMed: 11731287]
[Full Text: https://doi.org/10.1016/s0960-8966(01)00237-1]
</p>
</li>
<li>
<p class="mim-text-font">
Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P.
<strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong>
Ann. Neurol. 51: 750-759, 2002.
[PubMed: 12112081]
[Full Text: https://doi.org/10.1002/ana.10231]
</p>
</li>
<li>
<p class="mim-text-font">
Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F.
<strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong>
Neurology 59: 284-287, 2002.
[PubMed: 12136074]
[Full Text: https://doi.org/10.1212/wnl.59.2.284]
</p>
</li>
<li>
<p class="mim-text-font">
Jungbluth, H., Sewry, C., Brown, S. C., Manzur, A. Y., Mercuri, E., Bushby, K., Rowe, P., Johnson, M. A., Hughes, I., Kelsey, A., Dubowitz, V., Muntoni, F.
<strong>Minicore myopathy in children: a clinical and histopathological study of 19 cases.</strong>
Neuromusc. Disord. 10: 264-273, 2000.
[PubMed: 10838253]
[Full Text: https://doi.org/10.1016/s0960-8966(99)00125-x]
</p>
</li>
<li>
<p class="mim-text-font">
Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F.
<strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong>
Neurology 65: 1930-1935, 2005.
[PubMed: 16380615]
[Full Text: https://doi.org/10.1212/01.wnl.0000188870.37076.f2]
</p>
</li>
<li>
<p class="mim-text-font">
Jungbluth, H., Zhou, H., Sewry, C. A., Robb, S., Treves, S., Bitoun, M., Guicheney, P., Buj-Bello, A., Bonnemann, C., Muntoni, F.
<strong>Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene.</strong>
Neuromusc. Disord. 17: 338-345, 2007.
[PubMed: 17376685]
[Full Text: https://doi.org/10.1016/j.nmd.2007.01.016]
</p>
</li>
<li>
<p class="mim-text-font">
Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others.
<strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong>
Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.
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<strong>Atypical periodic paralysis and myalgia: a novel RYR1 phenotype.</strong>
Neurology 90: e412-e418, 2018. Note: Electronic Article.
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McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R.
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Cassandra L. Kniffin - updated : 02/24/2023<br>Cassandra L. Kniffin - updated : 5/20/2015<br>Cassandra L. Kniffin - updated : 12/2/2014<br>Cassandra L. Kniffin - updated : 7/24/2013<br>Cassandra L. Kniffin - updated : 1/14/2013<br>Cassandra L. Kniffin - updated : 2/23/2011<br>Cassandra L. Kniffin - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 8/26/2008<br>Cassandra L. Kniffin - updated : 4/6/2006<br>Victor A. McKusick - updated : 3/28/2005<br>Cassandra L. Kniffin - reorganized : 2/20/2003<br>Cassandra L. Kniffin - updated : 2/11/2003<br>Victor A. McKusick - updated : 9/17/2002<br>Orest Hurko - updated : 3/23/1999
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