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<title>
Entry
- #255310 - CONGENITAL MYOPATHY 4A, AUTOSOMAL DOMINANT; CMYO4A
- OMIM
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<span class="h4">#255310</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/255310"><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="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</a>
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<a href="#history">History</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(CONGENITAL MYOPATHY 4A, AUTOSOMAL DOMINANT) OR (TPM3)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=493&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0080102" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/255310" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:255310" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 240084007<br />
<strong>ORPHA:</strong> 2020<br />
<strong>DO:</strong> 0080102<br />
">ICD+</a>
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<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
255310
</span>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
CONGENITAL MYOPATHY 4A, AUTOSOMAL DOMINANT; CMYO4A
</span>
</h3>
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<div>
<br />
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
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<div>
<h4>
<span class="mim-font">
MYOPATHY, CONGENITAL, WITH FIBER-TYPE DISPROPORTION; CFTD<br />
FIBER-TYPE DISPROPORTION MYOPATHY, CONGENITAL; CFTDM<br />
NEMALINE MYOPATHY 1; NEM1<br />
CAP MYOPATHY 1, FORMERLY; CAPM1, FORMERLY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
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<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1184?start=-3&limit=10&highlight=1184">
1q21.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Congenital myopathy 4A, autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/255310"> 255310 </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">
TPM3
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191030"> 191030 </a>
</span>
</td>
</tr>
</tbody>
</table>
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<a href="/clinicalSynopsis/255310" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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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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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/255310" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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</ul>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thin habitus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4231078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4231078</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Long face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836047&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836047</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000276</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000276</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=729bf273c6a346c2f07ab0965824ffb2" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Face,Long-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=729bf273c6a346c2f07ab0965824ffb2&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 /> -
Thin face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849121&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849121</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000275</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000275" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000275</a>]</span><br /> -
Facial muscle 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 /> -
Retrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109515000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109515000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035353</a>, <a href="https://bioportal.bioontology.org/search?q=C3494422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3494422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000278</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Retrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ede3aa3495baae8accf26d8f779302ba&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 /> -
Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882&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> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- 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 />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Neck muscle weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000467" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000467</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">
- Decreased forced vital capacity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846678&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846678</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032341" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032341</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0032341" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0032341</a>]</span><br /> -
Restrictive respiratory involvement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5829499&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5829499</a>]</span><br /> -
Noninvasive ventilation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/428311008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">428311008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1997883&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1997883</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Chest deformities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238983&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238983</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Scapular winging <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240953&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240953</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003691" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003691</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003691" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003691</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>
<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> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Foot deformities <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229844004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229844004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016506&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016506</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001760</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001760</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">
- Congenital myopathy <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G71.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G71.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270960&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270960</a>]</span><br /> -
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
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 /> -
Generalized muscle weakness <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 hypotrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br /> -
Frequent falls <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0850703&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0850703</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002359" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002359</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002359" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002359</a>]</span><br /> -
Walking difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/719232003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">719232003</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/719.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0311394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0311394</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002355</a>]</span><br /> -
Difficulty running <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/282479002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">282479002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0560346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0560346</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009046" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009046</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009046" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009046</a>]</span><br /> -
Easy fatigability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003388</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003388" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003388</a>]</span><br /> -
Stiff muscles (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221170</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003552</a>]</span><br /> -
Hypertonicity (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56731001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56731001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41581000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41581000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026826&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026826</a>, <a href="https://bioportal.bioontology.org/search?q=C0235396&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235396</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001276</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001276" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001276</a>]</span><br /> -
Variable findings seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5829494&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5829494</a>]</span><br /> -
Hypotrophy of type 1 muscle fibers seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5829497&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5829497</a>]</span><br /> -
Type 1 fibers are at least 12% smaller than type 2 fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845126&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845126</a>]</span><br /> -
Increased numbers of type 1 fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850696&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850696</a>]</span><br /> -
Decreased numbers of type 2B fibers <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850697</a>]</span><br /> -
Congenital 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 /> -
Cap structures <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5829498&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5829498</a>]</span><br /> -
Nemaline rods <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 />
</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 /> -
Unsteady gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22631008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22631008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002317" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002317</a>]</span><br /> -
Waddling gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271706000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271706000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231712&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231712</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002515</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002515" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002515</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">
- Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Areflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37280007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37280007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234146</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001284" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001284</a>]</span><br />
</span>
</div>
</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 infancy or childhood<br /> -
Nonprogressive or slowly progressive<br /> -
Most patients remain ambulatory<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 tropomyosin 3 gene (TPM3, <a href="/entry/191030#0001">191030.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
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<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>
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</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 dominant congenital myopathy-4A (CMYO4A) is caused by heterozygous mutation in the TPM3 (<a href="/entry/191030">191030</a>) gene on chromosome 1q21.</p><p>Biallelic mutation in the TPM3 gene causes CMYO4B (<a href="/entry/609284">609284</a>), which shows overlapping but more severe clinical features.</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>
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<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Congenital myopathy-4A (CMYO4A) is an autosomal dominant disorder of the skeletal muscle characterized by the onset of muscle weakness in infancy or childhood. The severity and pattern of muscle weakness varies, but most affected individuals show mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability. Many patients have respiratory insufficiency with reduced vital capacity, sometimes requiring noninvasive ventilatory assistance. Other common features include myopathic facies, high-arched palate, myasthenia, scapular winging, and scoliosis. Histologic findings on skeletal muscle biopsy are variable, even in patients with the same mutation. Muscle fibers can contain nemaline rod inclusions, subsarcolemmal 'cap' structures, and fiber-type disproportion (<a href="#6" class="mim-tip-reference" title="Clarke, N. F., Kolski, H., Dye, D. E., Lim, E., Smith, R. L. L., Patel, R., Fahey, M. C., Bellance, R., Romero, N. B., Johnson, E. S., Labarre-Vila, A., Monnier, N., Laing, N. G., North, K. N. &lt;strong&gt;Mutations in TPM3 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Ann. Neurol. 63: 329-337, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18300303/&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;18300303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21308&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="18300303">Clarke et al., 2008</a>; <a href="#29" class="mim-tip-reference" title="Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F. &lt;strong&gt;Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.&lt;/strong&gt; Neuromusc. Disord. 20: 464-466, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20554445/&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;20554445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2010.05.012&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="20554445">Waddell et al., 2010</a>; <a href="#21" class="mim-tip-reference" title="Malfatti, E., Schaeffer, U., Chapon, F., Yang, Y., Eymard, B., Xu, R., Laporte, J., Romero, N. B. &lt;strong&gt;Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene.&lt;/strong&gt; Neuromusc. Disord. 23: 992-997, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24095155/&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;24095155&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.07.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24095155">Malfatti et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20554445+18300303+24095155" 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><p>For a discussion of genetic heterogeneity of nemaline myopathy, see <a href="/entry/256030">256030</a>.</p>
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</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Clinical Features</strong>
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</h4>
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<p><a href="#19" class="mim-tip-reference" title="Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A. &lt;strong&gt;Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1.&lt;/strong&gt; Am. J. Hum. Genet. 50: 576-583, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1347195/&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;1347195&lt;/a&gt;]" pmid="1347195">Laing et al. (1992)</a> reported a large 5-generation family with childhood-onset congenital myopathy inherited in an autosomal dominant pattern. The proband had normal motor development until approximately 10 years of age, when he developed symmetrical weakness in foot dorsiflexion. The weakness progressed during adolescence to involve the proximal limb muscles. He had difficulty running and dysphagia. He had atrophy of the lower limbs with pes cavus, but no sensory impairment. An affected uncle had facial weakness, mild weakness of the sternocleidomastoid and trapezius muscles, and wasting and weakness of the proximal and distal lower extremities with areflexia. All affected members had onset of similar symptoms by age 10 years. Serum creatine kinase was normal. Biopsy of the proband showed marked variation in muscle fiber size with numerous nemaline bodies within type 1 fibers. <a href="#19" class="mim-tip-reference" title="Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A. &lt;strong&gt;Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1.&lt;/strong&gt; Am. J. Hum. Genet. 50: 576-583, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1347195/&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;1347195&lt;/a&gt;]" pmid="1347195">Laing et al. (1992)</a> concluded that this family had a childhood-onset form of nemaline myopathy. In affected members of this family, <a href="#20" class="mim-tip-reference" title="Laing, N. G., Wilton, S. D., Akkari, P. A., Dorosz, S., Boundy, K., Kneebone, C., Blumbergs, P., White, S., Watkins, H., Love, D. R., Haan, E. &lt;strong&gt;A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.&lt;/strong&gt; Nature Genet. 9: 75-79, 1995. Note: Erratum: Nature Genet. 10: 249 only, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7704029/&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;7704029&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0195-75&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="7704029">Laing et al. (1995)</a> identified a heterozygous mutation in the TPM3 gene (M9R; <a href="/entry/191030#0001">191030.0001</a>) that segregated with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1347195+7704029" 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="Penisson-Besnier, I., Monnier, N., Toutain, A., Dubas, F., Laing, N. &lt;strong&gt;A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.&lt;/strong&gt; Neuromusc. Disord. 17: 330-337, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17376686/&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;17376686&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2007.01.017&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="17376686">Penisson-Besnier et al. (2007)</a> reported a large French family in which 8 members spanning 4 generations had congenital myopathy inherited in an autosomal dominant pattern. Age at onset of significant disease was usually in adulthood, but milder symptoms were often present since childhood. Most had delayed motor development, and some reported poor physical performances in childhood. Affected individuals were able to walk unaided, but had proximal muscle weakness. Other features included scoliosis, need for nocturnal ventilation, slender build, and long face. Skeletal muscle biopsies showed type 1 fiber predominance and nemaline rods in type 1 fibers. Genetic analysis identified a heterozygous mutation in the TPM3 gene (R168H; <a href="/entry/191030#0005">191030.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17376686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Clarke, N. F., Kolski, H., Dye, D. E., Lim, E., Smith, R. L. L., Patel, R., Fahey, M. C., Bellance, R., Romero, N. B., Johnson, E. S., Labarre-Vila, A., Monnier, N., Laing, N. G., North, K. N. &lt;strong&gt;Mutations in TPM3 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Ann. Neurol. 63: 329-337, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18300303/&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;18300303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21308&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="18300303">Clarke et al. (2008)</a> reported 11 patients from 6 unrelated families with CMYO4A associated with congenital fiber-type disproportion on muscle biopsy. The patients ranged from 3.5 to 56 years of age. Affected individuals had proximal limb girdle weakness, prominent weakness of neck flexion and ankle dorsiflexion, mild facial weakness, and mild ptosis. Some had scoliosis. The age of onset and severity varied, even within the same family. Many patients required nocturnal noninvasive ventilation despite remaining ambulant. Genetic analysis identified heterozygous mutations in the TPM3 gene (see, e.g., <a href="/entry/191030#0005">191030.0005</a>; <a href="/entry/191030#0007">191030.0007</a>; <a href="/entry/191030#0008">191030.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18300303" 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="#23" class="mim-tip-reference" title="Ohlsson, M., Fidzianska, A., Tajsharghi, H., Oldfors, A. &lt;strong&gt;TPM3 mutation in one of the original cases of cap disease.&lt;/strong&gt; Neurology 72: 1961-1963, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19487656/&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;19487656&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181a82659&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="19487656">Ohlsson et al. (2009)</a> reported a 38-year-old woman with congenital myopathy associated with cap structures on skeletal muscle biopsy who had previously been reported by <a href="#13" class="mim-tip-reference" title="Fidzianska, A. &lt;strong&gt;&#x27;Cap disease&#x27;--a failure in the correct muscle fibre formation.&lt;/strong&gt; J. Neurol. Sci. 201: 27-31, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12163190/&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;12163190&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-510x(02)00156-9&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="12163190">Fidzianska (2002)</a>. The patient had slowly progressive muscle weakness and scoliosis since childhood, but was not examined until age 18 years. At that time, she had long narrow face, high-arched palate, chest deformity, and thin underdeveloped muscles. Other features included impaired nocturnal ventilation. Skeletal muscle biopsy showed that 20 to 30% of muscle fibers had granular cap structures devoid of ATPase activities. Myofibrils forming the caps were clearly demarcated from the remaining fibers and had an abnormal sarcomere pattern. Nemaline rods and fiber-type disproportion were not observed. Genetic analysis identified a heterozygous missense mutation in the TPM3 gene (R168C; <a href="/entry/191030#0009">191030.0009</a>). The findings illustrated the phenotypic and histologic variability associated with TPM3 mutations, and suggested that cap disease is related to nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12163190+19487656" 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="De Paula, A. M., Franques, J., Fernandez, C., Monnier, N., Lunardi, J., Pellissier, J.-F., Figarella-Branger, D., Pouget, J. &lt;strong&gt;A TPM3 mutation causing cap myopathy.&lt;/strong&gt; Neuromusc. Disord. 19: 685-688, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19553118/&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;19553118&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2009.06.365&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="19553118">De Paula et al. (2009)</a> reported a 42-year-old man with cap myopathy associated with a heterozygous de novo mutation in the TPM3 gene (R168H; <a href="/entry/191030#0005">191030.0005</a>). The patient showed hypotonia in the first months of life, delayed motor development, and distal weakness of the lower limbs with frequent falls in childhood. At age 7 years, he had flat feet in valgus, long narrow face, high-arched palate, and mild lumbar hyperlordosis. Tendon reflexes were absent. The clinical course was stable until presentation at age 42 with inability to run, difficulty climbing stairs, and predominant distal muscle weakness. Skeletal muscle biopsy at age 7 years showed type 1 fiber hypotrophy. Biopsy at age 42 years showed only type 1 fibers, irregularity of fiber size, occasional central nuclei, and peripheral eosinophilic-basophilic densely stained substances consistent with 'caps.' The caps were present in about 10 to 15% of muscle fibers, were negative for ATPase staining, were present just beneath the sarcolemma, and consisted of abnormally arranged myofibrils. Z lines were thickened with some rod-like structures. The authors noted that this case had first been reported as a congenital myopathy with selective hypotrophy of type 1 fibers (<a href="#26" class="mim-tip-reference" title="Serratrice, G., Pellissier, J. F., Gastaut, J. L., Pouget, J. &lt;strong&gt;Congenital myopathy with selective hypotrophy of type I fibers.&lt;/strong&gt; Rev. Neurol. (Paris) 131: 813-816, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1221488/&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;1221488&lt;/a&gt;]" pmid="1221488">Serratrice et al., 1975</a>), and that the biopsy results discussed in that report would have been consistent with congenital fiber-type disproportion (CFTD). The findings suggested a relationship between nemaline myopathy, CFTD, and cap myopathy, and indicated that cap structures may develop over time. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1221488+19553118" 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="#29" class="mim-tip-reference" title="Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F. &lt;strong&gt;Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.&lt;/strong&gt; Neuromusc. Disord. 20: 464-466, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20554445/&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;20554445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2010.05.012&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="20554445">Waddell et al. (2010)</a> reported a man with cap myopathy associated with a de novo heterozygous mutation in the TPM3 gene (R168C; <a href="/entry/191030#0009">191030.0009</a>). He had mildly delayed motor development in early childhood, generalized hypotonia, and muscle weakness, particularly of the proximal lower limbs, ankle dorsiflexors, and neck. He had a long myopathic face with open mouth, high-arched palate, retrognathia, narrow chest, and mild scoliosis. At age 20 years, his pulmonary vital capacity was 37% of that predicted. Muscle biopsy taken at age 3 years showed increased variation in fiber size and subsarcolemmal protein inclusions in 25% of fibers, typical of caps. There was also type 1 fiber predominance. Caps stained strongly for several proteins, including tropomyosin, and electron microscopy showed disorganized thin filament structures containing Z band remnants. Nemaline rods were not present. Two-dimensional gel electrophoresis showed that the mutant protein accounted for about 50% of the TPM3 protein in sarcomeres, and <a href="#29" class="mim-tip-reference" title="Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F. &lt;strong&gt;Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.&lt;/strong&gt; Neuromusc. Disord. 20: 464-466, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20554445/&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;20554445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2010.05.012&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="20554445">Waddell et al. (2010)</a> postulated a dominant-negative effect, perhaps resulting from altered protein-protein interactions. <a href="#29" class="mim-tip-reference" title="Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F. &lt;strong&gt;Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.&lt;/strong&gt; Neuromusc. Disord. 20: 464-466, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20554445/&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;20554445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2010.05.012&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="20554445">Waddell et al. (2010)</a> noted that the R168C mutation had previously been reported in a patient with CFTD (patient 9 in <a href="#6" class="mim-tip-reference" title="Clarke, N. F., Kolski, H., Dye, D. E., Lim, E., Smith, R. L. L., Patel, R., Fahey, M. C., Bellance, R., Romero, N. B., Johnson, E. S., Labarre-Vila, A., Monnier, N., Laing, N. G., North, K. N. &lt;strong&gt;Mutations in TPM3 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Ann. Neurol. 63: 329-337, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18300303/&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;18300303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21308&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="18300303">Clarke et al., 2008</a>). That patient had marked type 1 fiber hypotrophy and type 2 fiber hypertrophy, but no caps. These findings indicated that the fiber type distribution pattern as well as the pattern of protein inclusions can vary widely even among patients with the same TPM3 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20554445+18300303" 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="Malfatti, E., Schaeffer, U., Chapon, F., Yang, Y., Eymard, B., Xu, R., Laporte, J., Romero, N. B. &lt;strong&gt;Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene.&lt;/strong&gt; Neuromusc. Disord. 23: 992-997, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24095155/&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;24095155&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.07.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24095155">Malfatti et al. (2013)</a> reported a man of French Canadian origin with early-onset myopathy and a de novo heterozygous R168C mutation in the TPM3 gene. He had typical clinical features of the disorder, with mildly delayed motor milestones, generalized hypotonia, proximal and distal muscle weakness, impaired respiratory function, long, narrow face, and high-arched palate. This clinical course was relatively stable over many years until age 32, when he had progressive dyspnea, severe fatigability, and respiratory failure associated with right cardiac failure. He recovered from this acute episode. Muscle biopsy showed type 1 fiber uniformity, subsarcolemmal caps in about 20% of fibers, typical nemaline rods in about 10% of fibers, and both caps and rods in about 5% of fibers. Electron microscopy demonstrated that the cap structures were composed of disorganized myofibrils and thickened Z bands; the nemaline rods had longitudinal and transverse striations and were surrounded by thin filaments. Some of the caps contained structures resembling small rods, and the intermyofibrillary network adjacent to caps or nemaline rods was composed of irregular and jagged Z lines. <a href="#21" class="mim-tip-reference" title="Malfatti, E., Schaeffer, U., Chapon, F., Yang, Y., Eymard, B., Xu, R., Laporte, J., Romero, N. B. &lt;strong&gt;Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene.&lt;/strong&gt; Neuromusc. Disord. 23: 992-997, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24095155/&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;24095155&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.07.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24095155">Malfatti et al. (2013)</a> emphasized that the combination of rods and caps had not previously been reported in the same patient, which suggested that the 2 patterns are pathogenetically related. The findings confirmed that nemaline myopathy and cap myopathy resulting from TPM3 mutations are part of a disease spectrum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24095155" 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="Schreckenbach, T., Schroder, J. M., Voit, T., Abicht, A., Neuen-Jacob, E., Roos, A., Bulst, S., Kuhl, C., Schulz, J. B., Weis, J., Claeys, K. G. &lt;strong&gt;Novel TPM3 mutation in a family with cap myopathy and review of the literature.&lt;/strong&gt; Neuromusc. Disord. 24: 117-124, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24239060/&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;24239060&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.10.002&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="24239060">Schreckenbach et al. (2014)</a> reported 3 patients spanning 3 generations of a family with autosomal dominant CMYO4A. The proband was a 45-year-old woman who presented with waddling gait and a mild proximal and distal lower limb weakness resulting in difficulties walking and climbing stairs. She had a history of delayed motor development with walking at 2 years and mild proximal weakness since early childhood. Physical examination as an adult showed muscle hypotrophy, a low BMI, long narrow face, high-arched palate, micrognathia, scoliosis, decreased or absent deep tendon reflexes, and winged scapulae. She did not have facial weakness or ophthalmoplegia. Her 20-year-old son had muscle hypotrophy and frequent falls since childhood and continued to have a mild waddling gait. He had a long face with high-arched palate, micrognathia, absent reflexes, scapular winging, pes planovalgus, and reduced pulmonary vital capacity. The mother of the proband had similar features of a mild myopathy since childhood and showed scoliosis and muscle hypotrophy; she died due of acute respiratory failure during a pulmonary infection. All had mild cardiac abnormalities. Skeletal muscle biopsy of the proband and her mother showed cap myopathy with type 1 fiber predominance. Genetic analysis identified a heterozygous mutation in the TPM3 gene in the proband and her son (L149I; <a href="/entry/191030#0012">191030.0012</a>); the mother of the proband was not tested. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24239060" 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="#22" class="mim-tip-reference" title="Marttila, M., Lehtokari, V.-L., Marston, S., Nyman, T. A., Barnerias, C., Beggs, A. H., Bertini, E., Ceyhan-Birsoy, O., Cintas, P., Gerard, M., Gilbert-Dussardier, B., Hogue, J. S., and 29 others. &lt;strong&gt;Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies.&lt;/strong&gt; Hum. Mutat. 35: 779-790, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24692096/&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;24692096&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24692096[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/10.1002/humu.22554&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="24692096">Marttila et al. (2014)</a> reported 11 unrelated families with CMYO4A due to heterozygous missense mutations in the TPM3 gene. The patients had proximal muscle weakness since infancy or early childhood with variable difficulties walking and running. Skeletal muscle biopsies showed nemaline myopathy, cap myopathy, and fiber-type disproportion, with no genotype/phenotype correlations. Six novel heterozygous mutations and several recurrent mutations affecting codon 168 (R168C, R168H) were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24692096" 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="#30" class="mim-tip-reference" title="Xu, H., Liu, H., Chen, T., Song, B., Zhu, J., Liu, X., Li, M., Luo, C. &lt;strong&gt;The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications.&lt;/strong&gt; Genes Dis. 8: 715-720, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34291143/&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;34291143&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=34291143[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.gendis.2020.01.010&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="34291143">Xu et al. (2021)</a> reported a 10-year-old Chinese girl with CMYO4A manifest as muscle weakness since early childhood, scoliosis, respiratory insufficiency, high-arched palate, long face, and myasthenia associated with a heterozygous mutation in the TPM3 gene (R168G; <a href="/entry/191030#0008">191030.0008</a>) that was inherited from her clinically unaffected father. Her brother, who also carried the mutation, had a milder phenotype. Muscle biopsy did not show abnormal rods or caps. The authors noted the intrafamilial variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34291143" 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="Bevilacqua, J. A., Contreras, J. P., Trangulao, A., Hernandez, U., Brochier, G., Diaz, J., Hughes, R., Campero, M., Romero, N. B. &lt;strong&gt;Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern.&lt;/strong&gt; Neuromusc. Disord. 32: 687-691, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35688744/&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;35688744&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2022.05.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="35688744">Bevilacqua et al. (2022)</a> reported a 47-year-old man with CMYO4A associated with a heterozygous missense mutation in the TPM3 gene (E237K; <a href="/entry/191030#0013">191030.0013</a>). He had a history of delayed motor development with gait impairment and poor exercise tolerance since childhood. The disorder was slowly progressive, and he developed a high-pitched nasal voice, increased weakness, and dyspnea with reduced vital capacity requiring noninvasive ventilation. At age 47, he had global hypotonia, ptosis and facial weakness, high-arched palate, retrognathia, and axial weakness. MRI showed fatty replacement of several muscle, including the tongue, proximal limb muscles, and some muscles of the legs. Muscle biopsy showed both fiber-type disproportion and caps; nemaline rods were not present. He had no family history of a similar disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35688744" 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 25 Brazilian families with a clinical diagnosis of nemaline myopathy, <a href="#15" class="mim-tip-reference" title="Gurgel-Giannetti, J., Souza, L. S., Yamamoto, G. L., Belisario, M., Lazar, M., Campos, W., Pavanello, R. C. M., Zatz, M., Reed, U., Zanoteli, E., Oliveira, A. B., Lehtokari, V.-L., Casella, E. B., Machado-Costa, M. C., Wallgren-Pettersson, C., Laing, N. G., Nigro, V., Vainzof, M. &lt;strong&gt;Nemaline myopathy in Brazilian patients: molecular and clinical characterization.&lt;/strong&gt; Int. J. Molec. Sci. 23: 11995, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36233295/&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;36233295&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=36233295[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/10.3390/ijms231911995&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="36233295">Gurgel-Giannetti et al. (2022)</a> found 1 (4%) who carried a heterozygous missense mutation in the TPM3 gene (R168C; <a href="/entry/191030#0009">191030.0009</a>). The mutation was present in a father and son (family 7) with congenital myopathy, scoliosis, and nocturnal hypoventilation; both were ambulatory. The findings suggested that mutations in the TPM3 gene are not a common cause of nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36233295" 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>Atypical Congenital Myopathy With Hypertonia</em></strong></p><p>
<a href="#11" class="mim-tip-reference" title="Donkervoort, S., Papadaki, M., de Winter, J. M., Neu, M. B., Kirschner, J., Bolduc, V., Yang, M. L., Gibbons, M. A., Hu, Y., Dastgir, J., Leach, M. E., Rutkowski, A., and 11 others. &lt;strong&gt;TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.&lt;/strong&gt; Ann. Neurol. 78: 982-994, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26418456/&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;26418456&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=26418456[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/10.1002/ana.24535&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="26418456">Donkervoort et al. (2015)</a> reported 2 unrelated children with a hypercontractile phenotype with congenital muscle stiffness resulting in arthrogryposis multiplex and significant disability. Both showed decreased fetal movements. One had transient respiratory distress in infancy and mildly delayed motor development. At age 4 years, he had stiff muscles, walked with a stiff gait, and showed thoracic kyphosis. The second child had similar features with more severe respiratory involvement and was ventilator-dependent. Neither child had muscle weakness, atrophy, or myokymia. Muscle biopsies in both patients showed mild myopathic changes, with variation in fiber size and mild type 1 or 2 fiber predominance. Although there was no clear evidence of nemaline rods, there were irregularities of the myofibrillar apparatus and 'mini-miliary' rods, as well as ultrastructural evidence of mitochondrial accumulation and/or Z-line streaming and broadening. In 1 patient, botulinum toxin injections resulted in improved range of motion. Each patient carried a de novo heterozygous deletion of a conserved residue in the TPM3 gene (E218del, <a href="/entry/191030#0010">191030.0010</a> and E224del, <a href="/entry/191030#0011">191030.0011</a>). In vitro studies showed that both mutations resulted in increased calcium sensitivity, increased active interaction of actin and the myosin complex, and increased filament sliding motility, consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26418456" 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 CMYO4A in the family reported by <a href="#24" class="mim-tip-reference" title="Penisson-Besnier, I., Monnier, N., Toutain, A., Dubas, F., Laing, N. &lt;strong&gt;A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.&lt;/strong&gt; Neuromusc. Disord. 17: 330-337, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17376686/&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;17376686&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2007.01.017&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="17376686">Penisson-Besnier et al. (2007)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17376686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a large kindred in which 10 living members had congenital myopathy inherited in an autosomal dominant pattern, Laing et al. (<a href="#18" class="mim-tip-reference" title="Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A. &lt;strong&gt;Assignment of nemaline myopathy (MIM 161800, NEM1) to chromosome 1. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 58: 1858, 1991."None>1991</a>, <a href="#19" class="mim-tip-reference" title="Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A. &lt;strong&gt;Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1.&lt;/strong&gt; Am. J. Hum. Genet. 50: 576-583, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1347195/&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;1347195&lt;/a&gt;]" pmid="1347195">1992</a>) found linkage to the APOA2 gene (<a href="/entry/107670">107670</a>) on chromosome 1 (maximum lod score of 3.80). The findings indicated that the putative disease gene lies between the genes for nerve growth factor-beta (NGFB; <a href="/entry/162030">162030</a>) at 1p13 and antithrombin III (AT3; <a href="/entry/107300">107300</a>) at 1q23-q25.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347195" 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 large family with autosomal dominant CMYO4A previously reported by <a href="#19" class="mim-tip-reference" title="Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A. &lt;strong&gt;Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1.&lt;/strong&gt; Am. J. Hum. Genet. 50: 576-583, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1347195/&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;1347195&lt;/a&gt;]" pmid="1347195">Laing et al. (1992)</a>, <a href="#20" class="mim-tip-reference" title="Laing, N. G., Wilton, S. D., Akkari, P. A., Dorosz, S., Boundy, K., Kneebone, C., Blumbergs, P., White, S., Watkins, H., Love, D. R., Haan, E. &lt;strong&gt;A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.&lt;/strong&gt; Nature Genet. 9: 75-79, 1995. Note: Erratum: Nature Genet. 10: 249 only, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7704029/&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;7704029&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0195-75&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="7704029">Laing et al. (1995)</a> identified a heterozygous mutation in the TPM3 gene (M9R; <a href="/entry/191030#0001">191030.0001</a>) that segregated with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1347195+7704029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a French family with autosomal dominant CMYO4A, <a href="#24" class="mim-tip-reference" title="Penisson-Besnier, I., Monnier, N., Toutain, A., Dubas, F., Laing, N. &lt;strong&gt;A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.&lt;/strong&gt; Neuromusc. Disord. 17: 330-337, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17376686/&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;17376686&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2007.01.017&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="17376686">Penisson-Besnier et al. (2007)</a> identified a heterozygous mutation in the TPM3 gene (R168H; <a href="/entry/191030#0005">191030.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17376686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Clarke, N. F., Kolski, H., Dye, D. E., Lim, E., Smith, R. L. L., Patel, R., Fahey, M. C., Bellance, R., Romero, N. B., Johnson, E. S., Labarre-Vila, A., Monnier, N., Laing, N. G., North, K. N. &lt;strong&gt;Mutations in TPM3 are a common cause of congenital fiber type disproportion.&lt;/strong&gt; Ann. Neurol. 63: 329-337, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18300303/&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;18300303&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.21308&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="18300303">Clarke et al. (2008)</a> identified 5 different heterozygous TPM3 mutations (see, e.g., <a href="/entry/191030#0005">191030.0005</a>; <a href="/entry/191030#0007">191030.0007</a>; <a href="/entry/191030#0008">191030.0008</a>), in affected members of 6 unrelated families with CMYO4A and congenital fiber-type disproportion (CFTD) on skeletal muscle biopsy. The mutations were identified among 23 unrelated probands with CFTD, making mutations in the TPM3 gene the most common cause of CFTD to that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18300303" 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 38-year-old woman with CMYO4A associated with cap structures on skeletal muscle biopsy who had previously been reported by <a href="#13" class="mim-tip-reference" title="Fidzianska, A. &lt;strong&gt;&#x27;Cap disease&#x27;--a failure in the correct muscle fibre formation.&lt;/strong&gt; J. Neurol. Sci. 201: 27-31, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12163190/&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;12163190&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-510x(02)00156-9&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="12163190">Fidzianska (2002)</a>, <a href="#23" class="mim-tip-reference" title="Ohlsson, M., Fidzianska, A., Tajsharghi, H., Oldfors, A. &lt;strong&gt;TPM3 mutation in one of the original cases of cap disease.&lt;/strong&gt; Neurology 72: 1961-1963, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19487656/&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;19487656&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/WNL.0b013e3181a82659&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="19487656">Ohlsson et al. (2009)</a> identified a heterozygous mutation in the TPM3 gene (R168C; <a href="/entry/191030#0009">191030.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12163190+19487656" 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="De Paula, A. M., Franques, J., Fernandez, C., Monnier, N., Lunardi, J., Pellissier, J.-F., Figarella-Branger, D., Pouget, J. &lt;strong&gt;A TPM3 mutation causing cap myopathy.&lt;/strong&gt; Neuromusc. Disord. 19: 685-688, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19553118/&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;19553118&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2009.06.365&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="19553118">De Paula et al. (2009)</a> reported a 42-year-old man with cap myopathy associated with a heterozygous de novo mutation in the TPM3 gene (R168H; <a href="/entry/191030#0005">191030.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19553118" 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="#29" class="mim-tip-reference" title="Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F. &lt;strong&gt;Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.&lt;/strong&gt; Neuromusc. Disord. 20: 464-466, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20554445/&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;20554445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2010.05.012&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="20554445">Waddell et al. (2010)</a> reported a man with CMYO4A and cap myopathy on skeletal muscle biopsy that was associated with a de novo heterozygous R168C mutation in the TPM3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20554445" 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="Malfatti, E., Schaeffer, U., Chapon, F., Yang, Y., Eymard, B., Xu, R., Laporte, J., Romero, N. B. &lt;strong&gt;Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene.&lt;/strong&gt; Neuromusc. Disord. 23: 992-997, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24095155/&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;24095155&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.07.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24095155">Malfatti et al. (2013)</a> reported a man of French Canadian origin with early-onset myopathy and a de novo heterozygous R168C mutation in the TPM3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24095155" 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 2 affected members of a family with autosomal dominant CMYO4A, <a href="#25" class="mim-tip-reference" title="Schreckenbach, T., Schroder, J. M., Voit, T., Abicht, A., Neuen-Jacob, E., Roos, A., Bulst, S., Kuhl, C., Schulz, J. B., Weis, J., Claeys, K. G. &lt;strong&gt;Novel TPM3 mutation in a family with cap myopathy and review of the literature.&lt;/strong&gt; Neuromusc. Disord. 24: 117-124, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24239060/&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;24239060&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2013.10.002&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="24239060">Schreckenbach et al. (2014)</a> identified a heterozygous missense mutation in the TPM3 gene (L149I; <a href="/entry/191030#0012">191030.0012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24239060" 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="#22" class="mim-tip-reference" title="Marttila, M., Lehtokari, V.-L., Marston, S., Nyman, T. A., Barnerias, C., Beggs, A. H., Bertini, E., Ceyhan-Birsoy, O., Cintas, P., Gerard, M., Gilbert-Dussardier, B., Hogue, J. S., and 29 others. &lt;strong&gt;Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies.&lt;/strong&gt; Hum. Mutat. 35: 779-790, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24692096/&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;24692096&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=24692096[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/10.1002/humu.22554&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="24692096">Marttila et al. (2014)</a> reported 11 unrelated families with CMYO4A due to heterozygous missense mutations in the TPM3 gene. Six novel heterozygous mutations and several recurrent mutations affecting codon 168 (R168C, R168H) were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24692096" 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="#30" class="mim-tip-reference" title="Xu, H., Liu, H., Chen, T., Song, B., Zhu, J., Liu, X., Li, M., Luo, C. &lt;strong&gt;The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications.&lt;/strong&gt; Genes Dis. 8: 715-720, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34291143/&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;34291143&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=34291143[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.gendis.2020.01.010&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="34291143">Xu et al. (2021)</a> reported a 10-year-old Chinese girl with CMYO4A associated with a heterozygous R168G mutation in the TPM3 gene (R168G; <a href="/entry/191030#0008">191030.0008</a>) that was inherited from her clinically unaffected father. Her brother, who also carried the mutation, had a milder phenotype. The authors noted the intrafamilial variability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34291143" 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 47-year-old man with CMYO4A, <a href="#2" class="mim-tip-reference" title="Bevilacqua, J. A., Contreras, J. P., Trangulao, A., Hernandez, U., Brochier, G., Diaz, J., Hughes, R., Campero, M., Romero, N. B. &lt;strong&gt;Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern.&lt;/strong&gt; Neuromusc. Disord. 32: 687-691, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35688744/&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;35688744&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2022.05.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="35688744">Bevilacqua et al. (2022)</a> identified a heterozygous mutation in the TPM3 gene (E237K; <a href="/entry/191030#0013">191030.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35688744" 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 25 Brazilian families with a clinical diagnosis of nemaline myopathy, <a href="#15" class="mim-tip-reference" title="Gurgel-Giannetti, J., Souza, L. S., Yamamoto, G. L., Belisario, M., Lazar, M., Campos, W., Pavanello, R. C. M., Zatz, M., Reed, U., Zanoteli, E., Oliveira, A. B., Lehtokari, V.-L., Casella, E. B., Machado-Costa, M. C., Wallgren-Pettersson, C., Laing, N. G., Nigro, V., Vainzof, M. &lt;strong&gt;Nemaline myopathy in Brazilian patients: molecular and clinical characterization.&lt;/strong&gt; Int. J. Molec. Sci. 23: 11995, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36233295/&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;36233295&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=36233295[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/10.3390/ijms231911995&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="36233295">Gurgel-Giannetti et al. (2022)</a> found 1 (4%) who carried a heterozygous missense mutation in the TPM3 gene (R168C; <a href="/entry/191030#0009">191030.0009</a>). The mutation was present in a father and son (family 7) with congenital myopathy, scoliosis, and nocturnal hypoventilation; both were ambulatory. The findings suggested that mutations in the TPM3 gene are not a common cause of nemaline myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36233295" 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="#8" class="mim-tip-reference" title="Corbett, M. A., Robinson, C. S., Dunglison, G. F., Yang, N., Joya, J. E., Stewart, A. W., Schnell, C., Gunning, P. W., North, K. N., Hardeman, E. C. &lt;strong&gt;A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy.&lt;/strong&gt; Hum. Molec. Genet. 10: 317-328, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11157795/&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;11157795&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.4.317&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="11157795">Corbett et al. (2001)</a> generated a transgenic mouse model expressing an autosomal dominant mutant of TPM3 (M9R; <a href="/entry/191030#0001">191030.0001</a>) previously identified in a human patient with nemaline myopathy. Rods were found in all muscles, but to varying extents which did not correlate with the amount of mutant protein present. In addition, a pathologic feature not commonly associated with this disorder, cytoplasmic bodies, was found in the mouse and subsequently identified in human samples. Hypertrophy of fast, type 2B (glycolytic) fibers was apparent at 2 months of age. Muscle weakness was apparent in mice at 5 to 6 months of age, mimicking the late onset observed in humans with this mutation. The onset of weakness correlated with an age-related decrease in fiber diameter and suggested that early onset may be prevented by hypertrophy of fast, glycolytic fibers. The authors suggested that the clinical phenotype may be precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11157795" 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>'Congenital fiber-type disproportion' (CFTD) myopathy is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. <a href="#7" class="mim-tip-reference" title="Clarke, N. F., North, K. N. &lt;strong&gt;Congenital fiber type disproportion--30 years on.&lt;/strong&gt; J. Neuropath. Exp. Neurol. 62: 977-989, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14575234/&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;14575234&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/jnen/62.10.977&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="14575234">Clarke and North (2003)</a> stated that the diagnosis of 'congenital fiber-type disproportion' as a disease entity is one of exclusion. They also suggested that the nonspecific histologic findings should be termed 'fiber size disproportion,' thus reserving the term CFTD for those cases in which no secondary cause can be found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14575234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Brooke, M. H. &lt;strong&gt;Congenital fiber type disproportion. In: Kakulas, B. A.: Clinical Studies in Myology. Proc. of the 2nd Int. Cong. on Muscle Diseases, Perth, Australia, 1971. Part 2.&lt;/strong&gt; Amsterdam: Excerpta Medica (pub.) 1973. Pp. 147-159."None>Brooke (1973)</a> reported 12 cases and coined the term 'congenital fiber-type disproportion.' All patients had hypotrophy of type 1 muscle fibers, which were at least 12% smaller than either type 2A or type 2B fibers. Clinical features included congenital hypotonia, generalized weakness, and failure to thrive. Other features included long, thin face, scoliosis, high-arched palate, and multiple joint contractures. One patient had an affected parent.</p><p><a href="#5" class="mim-tip-reference" title="Cavanagh, N. P., Lake, B. D., McMeniman, P. &lt;strong&gt;Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.&lt;/strong&gt; Arch. Dis. Child. 54: 735-743, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/507896/&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;507896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.54.10.735&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="507896">Cavanagh et al. (1979)</a> described 9 children with congenital fiber-type disproportion. Hypotonia, joint laxity, and congenital dislocation of the hip were the usual features. Muscle biopsies showed type 1 fibers that were smaller than the largest type 2 fibers by at least 13.5%. The natural history of the disorder was variable, with some children having fatal respiratory events. The parents in 1 case were second cousins. One mother was said to have weak legs in childhood, and another patient was said to have 2 affected paternal cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=507896" 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="#27" class="mim-tip-reference" title="Somer, M. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Helsinki, Finland 5/27/1981."None>Somer (1981)</a> reported a 22-year-old man with muscle weakness and marfanoid features, including scoliosis. He had been a floppy infant. He worked as a television technician but could not lift TVs. Muscle biopsy showed type 1 fibers to be smaller than type 2 fibers. Type 2A fibers showed compensatory hypertrophy, and type 2B fibers were lacking.</p><p><a href="#16" class="mim-tip-reference" title="Jaffe, M., Shapira, J., Borochowitz, Z. &lt;strong&gt;Familial congenital fiber type disproportion (CFTD) with an autosomal recessive inheritance.&lt;/strong&gt; Clin. Genet. 33: 33-37, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3342545/&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;3342545&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1988.tb04261.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="3342545">Jaffe et al. (1988)</a> described this disorder in a 12-year-old male and his infant sister. The parents were healthy and unrelated, suggesting autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3342545" 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="Clarke, N. F., North, K. N. &lt;strong&gt;Congenital fiber type disproportion--30 years on.&lt;/strong&gt; J. Neuropath. Exp. Neurol. 62: 977-989, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14575234/&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;14575234&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/jnen/62.10.977&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="14575234">Clarke and North (2003)</a> clarified the definition of CFTD through a comprehensive literature review and analysis. Of 218 reported cases of fiber size disproportion on muscle biopsy, they classified 67 cases as having CFTD, using inclusion criteria of (1) clinical muscle weakness and/or hypotonia, and (2) mean type 1 fiber diameter at least 12% smaller than mean type 2 fiber diameter. Exclusion criteria consisted of insufficient clinical information; a coexisting disorder of muscle or the nervous system; 2 or more syndromal features present; histologic features of a muscular dystrophy; and a coefficient of variation greater than 250 for type 2 fibers. In most cases, limb weakness was greatest in the limb girdle and proximal muscle groups, although many children had generalized muscle weakness. There was variable facial weakness (42% of patients), ophthalmoplegia (19%), and severe respiratory involvement (18%). Long face and high-arched palate were commonly reported. Reflexes were usually decreased or absent. Many patients had contractures, either at birth or developing later, of the ankles (10 cases), fingers (4 cases), hips (3 cases), elbows (3 cases), and knees (2 cases). Fifteen patients had scoliosis. Only 2 patients had cardiac involvement: dilated cardiomyopathy and atrial fibrillation, respectively (<a href="#1" class="mim-tip-reference" title="Banwell, B. L., Becker, L. E., Jay, V., Taylor, G. P., Vajsar, J. &lt;strong&gt;Cardiac manifestations of congenital fiber-type disproportion myopathy.&lt;/strong&gt; J. Child Neurol. 14: 83-87, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10073429/&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;10073429&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1177/088307389901400205&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="10073429">Banwell et al., 1999</a>). Two patients had intellectual disability and 3 males had cryptorchidism. Fifty patients had type 1 fiber diameters that were 25% smaller than type 2, and these patients tended to have a more severe clinical phenotype. Family history was present in 43% of families, suggesting that genetics may play a role in a subset of patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14575234+10073429" 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="Fardeau, M., Harpey, J. P., Caille, B. &lt;strong&gt;Disproportion congenitale des differents types de fibre musculaire, avec petitesse relative des fibres de type I: documents morphologiques concernant les biopsies musculaires prelevees chez trois membres d&#x27;une meme famille.&lt;/strong&gt; Rev. Neurol. 131: 745-766, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/130671/&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;130671&lt;/a&gt;]" pmid="130671">Fardeau et al. (1975)</a> reported a family with CFTD in which the father and 2 sisters were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=130671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Curless, R. G., Nelson, M. B. &lt;strong&gt;Congenital fiber type disproportion in identical twins.&lt;/strong&gt; Ann. Neurol. 2: 455-459, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/569460/&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;569460&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410020603&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="569460">Curless and Nelson (1977)</a> described this form of myopathy in identical twins. This occurrence in sibs and the parental consanguinity suggested autosomal recessive inheritance. Parental involvement pointing to an autosomal dominant mode of transmission for CFTD was reported by <a href="#17" class="mim-tip-reference" title="Kula, R. W., Sher, J. H., Shafiq, S. A., Hardy-Stashin, J. &lt;strong&gt;Variability of clinical pathological manifestations in familial fiber type disproportion.&lt;/strong&gt; Trans. Am. Neurol. Assoc. 105: 416-418, 1980."None>Kula et al. (1980)</a> and <a href="#28" class="mim-tip-reference" title="Sulaiman, A., Swick, H. M., Kinder, D. S. &lt;strong&gt;Congenital fibre type disproportion with unusual clinico-pathologic manifestations.&lt;/strong&gt; J. Neurol. Neurosurg. Psychiat. 46: 175-182, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6842223/&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;6842223&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jnnp.46.2.175&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="6842223">Sulaiman et al. (1983)</a>. See also CFTDX (<a href="/entry/300580">300580</a>), which has been mapped to chromosome Xq13.1-q22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6842223+569460" 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="#14" class="mim-tip-reference" title="Gerdes, A. M., Petersen, M. B., Schroder, H. D., Wulff, K., Brondum-Nielsen, K. &lt;strong&gt;Congenital myopathy with fiber type disproportion: a family with a chromosomal translocation t(10;17) may indicate candidate gene regions.&lt;/strong&gt; Clin. Genet. 45: 11-16, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7908614/&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;7908614&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1994.tb03982.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="7908614">Gerdes et al. (1994)</a> reported a child with congenital fiber-type disproportion who was born with arthrogryposis multiplex congenita, dislocation of the hips, and mild scoliosis. By age 5 years, she had developed marked muscle weakness. Cytogenetic analysis identified a balanced chromosomal translocation, t(10;17)(p11.2;q25), transmitted by the clinically healthy mother. Maternal uniparental disomy for loci on either chromosome 10 or chromosome 17 was excluded. Although the mother had normal muscle strength and mass, muscle biopsy showed type 1 fiber predominance and EMG showed myopathic changes. <a href="#14" class="mim-tip-reference" title="Gerdes, A. M., Petersen, M. B., Schroder, H. D., Wulff, K., Brondum-Nielsen, K. &lt;strong&gt;Congenital myopathy with fiber type disproportion: a family with a chromosomal translocation t(10;17) may indicate candidate gene regions.&lt;/strong&gt; Clin. Genet. 45: 11-16, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7908614/&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;7908614&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1994.tb03982.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="7908614">Gerdes et al. (1994)</a> suggested that congenital fiber-type disproportion in this family was dominantly inherited with variable expressivity, and that the translocation breakpoints may represent candidate gene regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7908614" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Brooke1969" class="mim-tip-reference" title="Brooke, M. H., Engel, W. K. &lt;strong&gt;The histographic analysis of human muscle biopsies with regard to fibre types. IV. Children&#x27;s biopsies.&lt;/strong&gt; Neurology 19: 591-605, 1969.">Brooke and Engel (1969)</a>
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<a id="Banwell1999" class="mim-anchor"></a>
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Banwell, B. L., Becker, L. E., Jay, V., Taylor, G. P., Vajsar, J.
<strong>Cardiac manifestations of congenital fiber-type disproportion myopathy.</strong>
J. Child Neurol. 14: 83-87, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10073429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10073429</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10073429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1177/088307389901400205" target="_blank">Full Text</a>]
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Bevilacqua, J. A., Contreras, J. P., Trangulao, A., Hernandez, U., Brochier, G., Diaz, J., Hughes, R., Campero, M., Romero, N. B.
<strong>Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern.</strong>
Neuromusc. Disord. 32: 687-691, 2022.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35688744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35688744</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35688744" 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.2022.05.014" target="_blank">Full Text</a>]
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<a id="Brooke1969" class="mim-anchor"></a>
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Brooke, M. H., Engel, W. K.
<strong>The histographic analysis of human muscle biopsies with regard to fibre types. IV. Children's biopsies.</strong>
Neurology 19: 591-605, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5814304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5814304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5814304" 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.19.6.591" target="_blank">Full Text</a>]
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<a id="Brooke1973" class="mim-anchor"></a>
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Brooke, M. H.
<strong>Congenital fiber type disproportion. In: Kakulas, B. A.: Clinical Studies in Myology. Proc. of the 2nd Int. Cong. on Muscle Diseases, Perth, Australia, 1971. Part 2.</strong>
Amsterdam: Excerpta Medica (pub.) 1973. Pp. 147-159.
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[<a href="https://doi.org/10.1136/adc.54.10.735" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.21308" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/jnen/62.10.977" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/10.4.317" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410020603" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2009.06.365" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.24535" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-510x(02)00156-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1994.tb03982.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.3390/ijms231911995" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1988.tb04261.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng0195-75" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2013.07.003" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.22554" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/WNL.0b013e3181a82659" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2013.10.002" target="_blank">Full Text</a>]
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Sulaiman, A., Swick, H. M., Kinder, D. S.
<strong>Congenital fibre type disproportion with unusual clinico-pathologic manifestations.</strong>
J. Neurol. Neurosurg. Psychiat. 46: 175-182, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6842223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6842223</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6842223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jnnp.46.2.175" target="_blank">Full Text</a>]
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<a id="Waddell2010" class="mim-anchor"></a>
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Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F.
<strong>Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.</strong>
Neuromusc. Disord. 20: 464-466, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20554445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20554445</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20554445" 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.2010.05.012" target="_blank">Full Text</a>]
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Xu, H., Liu, H., Chen, T., Song, B., Zhu, J., Liu, X., Li, M., Luo, C.
<strong>The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications.</strong>
Genes Dis. 8: 715-720, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34291143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34291143</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34291143[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=34291143" 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.gendis.2020.01.010" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 06/01/2023
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Cassandra L. Kniffin - updated : 03/05/2023<br>Cassandra L. Kniffin - updated : 9/28/2009<br>Cassandra L. Kniffin - updated : 12/28/2007<br>Cassandra L. Kniffin - updated : 9/18/2007<br>Cassandra L. Kniffin - updated : 5/3/2006<br>Cassandra L. Kniffin - updated : 3/14/2006<br>Cassandra L. Kniffin - reorganized : 7/13/2005<br>Cassandra L. Kniffin - updated : 7/1/2005<br>Victor A. McKusick - updated : 1/8/2003
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Victor A. McKusick : 6/4/1986
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alopez : 07/16/2024
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<strong>#</strong> 255310
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CONGENITAL MYOPATHY 4A, AUTOSOMAL DOMINANT; CMYO4A
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<em>Alternative titles; symbols</em>
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MYOPATHY, CONGENITAL, WITH FIBER-TYPE DISPROPORTION; CFTD<br />
FIBER-TYPE DISPROPORTION MYOPATHY, CONGENITAL; CFTDM<br />
NEMALINE MYOPATHY 1; NEM1<br />
CAP MYOPATHY 1, FORMERLY; CAPM1, FORMERLY
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<strong>SNOMEDCT:</strong> 240084007; &nbsp;
<strong>ORPHA:</strong> 2020; &nbsp;
<strong>DO:</strong> 0080102; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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1q21.3
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Congenital myopathy 4A, autosomal dominant
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255310
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Autosomal dominant
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3
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TPM3
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191030
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that autosomal dominant congenital myopathy-4A (CMYO4A) is caused by heterozygous mutation in the TPM3 (191030) gene on chromosome 1q21.</p><p>Biallelic mutation in the TPM3 gene causes CMYO4B (609284), which shows overlapping but more severe clinical features.</p>
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<strong>Description</strong>
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<p>Congenital myopathy-4A (CMYO4A) is an autosomal dominant disorder of the skeletal muscle characterized by the onset of muscle weakness in infancy or childhood. The severity and pattern of muscle weakness varies, but most affected individuals show mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability. Many patients have respiratory insufficiency with reduced vital capacity, sometimes requiring noninvasive ventilatory assistance. Other common features include myopathic facies, high-arched palate, myasthenia, scapular winging, and scoliosis. Histologic findings on skeletal muscle biopsy are variable, even in patients with the same mutation. Muscle fibers can contain nemaline rod inclusions, subsarcolemmal 'cap' structures, and fiber-type disproportion (Clarke et al., 2008; Waddell et al., 2010; Malfatti et al., 2013). </p><p>For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000).</p><p>For a discussion of genetic heterogeneity of nemaline myopathy, see 256030.</p>
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<strong>Clinical Features</strong>
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<p>Laing et al. (1992) reported a large 5-generation family with childhood-onset congenital myopathy inherited in an autosomal dominant pattern. The proband had normal motor development until approximately 10 years of age, when he developed symmetrical weakness in foot dorsiflexion. The weakness progressed during adolescence to involve the proximal limb muscles. He had difficulty running and dysphagia. He had atrophy of the lower limbs with pes cavus, but no sensory impairment. An affected uncle had facial weakness, mild weakness of the sternocleidomastoid and trapezius muscles, and wasting and weakness of the proximal and distal lower extremities with areflexia. All affected members had onset of similar symptoms by age 10 years. Serum creatine kinase was normal. Biopsy of the proband showed marked variation in muscle fiber size with numerous nemaline bodies within type 1 fibers. Laing et al. (1992) concluded that this family had a childhood-onset form of nemaline myopathy. In affected members of this family, Laing et al. (1995) identified a heterozygous mutation in the TPM3 gene (M9R; 191030.0001) that segregated with the disorder. </p><p>Penisson-Besnier et al. (2007) reported a large French family in which 8 members spanning 4 generations had congenital myopathy inherited in an autosomal dominant pattern. Age at onset of significant disease was usually in adulthood, but milder symptoms were often present since childhood. Most had delayed motor development, and some reported poor physical performances in childhood. Affected individuals were able to walk unaided, but had proximal muscle weakness. Other features included scoliosis, need for nocturnal ventilation, slender build, and long face. Skeletal muscle biopsies showed type 1 fiber predominance and nemaline rods in type 1 fibers. Genetic analysis identified a heterozygous mutation in the TPM3 gene (R168H; 191030.0005). </p><p>Clarke et al. (2008) reported 11 patients from 6 unrelated families with CMYO4A associated with congenital fiber-type disproportion on muscle biopsy. The patients ranged from 3.5 to 56 years of age. Affected individuals had proximal limb girdle weakness, prominent weakness of neck flexion and ankle dorsiflexion, mild facial weakness, and mild ptosis. Some had scoliosis. The age of onset and severity varied, even within the same family. Many patients required nocturnal noninvasive ventilation despite remaining ambulant. Genetic analysis identified heterozygous mutations in the TPM3 gene (see, e.g., 191030.0005; 191030.0007; 191030.0008). </p><p>Ohlsson et al. (2009) reported a 38-year-old woman with congenital myopathy associated with cap structures on skeletal muscle biopsy who had previously been reported by Fidzianska (2002). The patient had slowly progressive muscle weakness and scoliosis since childhood, but was not examined until age 18 years. At that time, she had long narrow face, high-arched palate, chest deformity, and thin underdeveloped muscles. Other features included impaired nocturnal ventilation. Skeletal muscle biopsy showed that 20 to 30% of muscle fibers had granular cap structures devoid of ATPase activities. Myofibrils forming the caps were clearly demarcated from the remaining fibers and had an abnormal sarcomere pattern. Nemaline rods and fiber-type disproportion were not observed. Genetic analysis identified a heterozygous missense mutation in the TPM3 gene (R168C; 191030.0009). The findings illustrated the phenotypic and histologic variability associated with TPM3 mutations, and suggested that cap disease is related to nemaline myopathy. </p><p>De Paula et al. (2009) reported a 42-year-old man with cap myopathy associated with a heterozygous de novo mutation in the TPM3 gene (R168H; 191030.0005). The patient showed hypotonia in the first months of life, delayed motor development, and distal weakness of the lower limbs with frequent falls in childhood. At age 7 years, he had flat feet in valgus, long narrow face, high-arched palate, and mild lumbar hyperlordosis. Tendon reflexes were absent. The clinical course was stable until presentation at age 42 with inability to run, difficulty climbing stairs, and predominant distal muscle weakness. Skeletal muscle biopsy at age 7 years showed type 1 fiber hypotrophy. Biopsy at age 42 years showed only type 1 fibers, irregularity of fiber size, occasional central nuclei, and peripheral eosinophilic-basophilic densely stained substances consistent with 'caps.' The caps were present in about 10 to 15% of muscle fibers, were negative for ATPase staining, were present just beneath the sarcolemma, and consisted of abnormally arranged myofibrils. Z lines were thickened with some rod-like structures. The authors noted that this case had first been reported as a congenital myopathy with selective hypotrophy of type 1 fibers (Serratrice et al., 1975), and that the biopsy results discussed in that report would have been consistent with congenital fiber-type disproportion (CFTD). The findings suggested a relationship between nemaline myopathy, CFTD, and cap myopathy, and indicated that cap structures may develop over time. </p><p>Waddell et al. (2010) reported a man with cap myopathy associated with a de novo heterozygous mutation in the TPM3 gene (R168C; 191030.0009). He had mildly delayed motor development in early childhood, generalized hypotonia, and muscle weakness, particularly of the proximal lower limbs, ankle dorsiflexors, and neck. He had a long myopathic face with open mouth, high-arched palate, retrognathia, narrow chest, and mild scoliosis. At age 20 years, his pulmonary vital capacity was 37% of that predicted. Muscle biopsy taken at age 3 years showed increased variation in fiber size and subsarcolemmal protein inclusions in 25% of fibers, typical of caps. There was also type 1 fiber predominance. Caps stained strongly for several proteins, including tropomyosin, and electron microscopy showed disorganized thin filament structures containing Z band remnants. Nemaline rods were not present. Two-dimensional gel electrophoresis showed that the mutant protein accounted for about 50% of the TPM3 protein in sarcomeres, and Waddell et al. (2010) postulated a dominant-negative effect, perhaps resulting from altered protein-protein interactions. Waddell et al. (2010) noted that the R168C mutation had previously been reported in a patient with CFTD (patient 9 in Clarke et al., 2008). That patient had marked type 1 fiber hypotrophy and type 2 fiber hypertrophy, but no caps. These findings indicated that the fiber type distribution pattern as well as the pattern of protein inclusions can vary widely even among patients with the same TPM3 mutation. </p><p>Malfatti et al. (2013) reported a man of French Canadian origin with early-onset myopathy and a de novo heterozygous R168C mutation in the TPM3 gene. He had typical clinical features of the disorder, with mildly delayed motor milestones, generalized hypotonia, proximal and distal muscle weakness, impaired respiratory function, long, narrow face, and high-arched palate. This clinical course was relatively stable over many years until age 32, when he had progressive dyspnea, severe fatigability, and respiratory failure associated with right cardiac failure. He recovered from this acute episode. Muscle biopsy showed type 1 fiber uniformity, subsarcolemmal caps in about 20% of fibers, typical nemaline rods in about 10% of fibers, and both caps and rods in about 5% of fibers. Electron microscopy demonstrated that the cap structures were composed of disorganized myofibrils and thickened Z bands; the nemaline rods had longitudinal and transverse striations and were surrounded by thin filaments. Some of the caps contained structures resembling small rods, and the intermyofibrillary network adjacent to caps or nemaline rods was composed of irregular and jagged Z lines. Malfatti et al. (2013) emphasized that the combination of rods and caps had not previously been reported in the same patient, which suggested that the 2 patterns are pathogenetically related. The findings confirmed that nemaline myopathy and cap myopathy resulting from TPM3 mutations are part of a disease spectrum. </p><p>Schreckenbach et al. (2014) reported 3 patients spanning 3 generations of a family with autosomal dominant CMYO4A. The proband was a 45-year-old woman who presented with waddling gait and a mild proximal and distal lower limb weakness resulting in difficulties walking and climbing stairs. She had a history of delayed motor development with walking at 2 years and mild proximal weakness since early childhood. Physical examination as an adult showed muscle hypotrophy, a low BMI, long narrow face, high-arched palate, micrognathia, scoliosis, decreased or absent deep tendon reflexes, and winged scapulae. She did not have facial weakness or ophthalmoplegia. Her 20-year-old son had muscle hypotrophy and frequent falls since childhood and continued to have a mild waddling gait. He had a long face with high-arched palate, micrognathia, absent reflexes, scapular winging, pes planovalgus, and reduced pulmonary vital capacity. The mother of the proband had similar features of a mild myopathy since childhood and showed scoliosis and muscle hypotrophy; she died due of acute respiratory failure during a pulmonary infection. All had mild cardiac abnormalities. Skeletal muscle biopsy of the proband and her mother showed cap myopathy with type 1 fiber predominance. Genetic analysis identified a heterozygous mutation in the TPM3 gene in the proband and her son (L149I; 191030.0012); the mother of the proband was not tested. </p><p>Marttila et al. (2014) reported 11 unrelated families with CMYO4A due to heterozygous missense mutations in the TPM3 gene. The patients had proximal muscle weakness since infancy or early childhood with variable difficulties walking and running. Skeletal muscle biopsies showed nemaline myopathy, cap myopathy, and fiber-type disproportion, with no genotype/phenotype correlations. Six novel heterozygous mutations and several recurrent mutations affecting codon 168 (R168C, R168H) were identified. </p><p>Xu et al. (2021) reported a 10-year-old Chinese girl with CMYO4A manifest as muscle weakness since early childhood, scoliosis, respiratory insufficiency, high-arched palate, long face, and myasthenia associated with a heterozygous mutation in the TPM3 gene (R168G; 191030.0008) that was inherited from her clinically unaffected father. Her brother, who also carried the mutation, had a milder phenotype. Muscle biopsy did not show abnormal rods or caps. The authors noted the intrafamilial variability. </p><p>Bevilacqua et al. (2022) reported a 47-year-old man with CMYO4A associated with a heterozygous missense mutation in the TPM3 gene (E237K; 191030.0013). He had a history of delayed motor development with gait impairment and poor exercise tolerance since childhood. The disorder was slowly progressive, and he developed a high-pitched nasal voice, increased weakness, and dyspnea with reduced vital capacity requiring noninvasive ventilation. At age 47, he had global hypotonia, ptosis and facial weakness, high-arched palate, retrognathia, and axial weakness. MRI showed fatty replacement of several muscle, including the tongue, proximal limb muscles, and some muscles of the legs. Muscle biopsy showed both fiber-type disproportion and caps; nemaline rods were not present. He had no family history of a similar disorder. </p><p>Among 25 Brazilian families with a clinical diagnosis of nemaline myopathy, Gurgel-Giannetti et al. (2022) found 1 (4%) who carried a heterozygous missense mutation in the TPM3 gene (R168C; 191030.0009). The mutation was present in a father and son (family 7) with congenital myopathy, scoliosis, and nocturnal hypoventilation; both were ambulatory. The findings suggested that mutations in the TPM3 gene are not a common cause of nemaline myopathy. </p><p><strong><em>Atypical Congenital Myopathy With Hypertonia</em></strong></p><p>
Donkervoort et al. (2015) reported 2 unrelated children with a hypercontractile phenotype with congenital muscle stiffness resulting in arthrogryposis multiplex and significant disability. Both showed decreased fetal movements. One had transient respiratory distress in infancy and mildly delayed motor development. At age 4 years, he had stiff muscles, walked with a stiff gait, and showed thoracic kyphosis. The second child had similar features with more severe respiratory involvement and was ventilator-dependent. Neither child had muscle weakness, atrophy, or myokymia. Muscle biopsies in both patients showed mild myopathic changes, with variation in fiber size and mild type 1 or 2 fiber predominance. Although there was no clear evidence of nemaline rods, there were irregularities of the myofibrillar apparatus and 'mini-miliary' rods, as well as ultrastructural evidence of mitochondrial accumulation and/or Z-line streaming and broadening. In 1 patient, botulinum toxin injections resulted in improved range of motion. Each patient carried a de novo heterozygous deletion of a conserved residue in the TPM3 gene (E218del, 191030.0010 and E224del, 191030.0011). In vitro studies showed that both mutations resulted in increased calcium sensitivity, increased active interaction of actin and the myosin complex, and increased filament sliding motility, consistent with a gain of function. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of CMYO4A in the family reported by Penisson-Besnier et al. (2007) was consistent with autosomal dominant inheritance. </p>
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<strong>Mapping</strong>
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<p>In a large kindred in which 10 living members had congenital myopathy inherited in an autosomal dominant pattern, Laing et al. (1991, 1992) found linkage to the APOA2 gene (107670) on chromosome 1 (maximum lod score of 3.80). The findings indicated that the putative disease gene lies between the genes for nerve growth factor-beta (NGFB; 162030) at 1p13 and antithrombin III (AT3; 107300) at 1q23-q25.1. </p>
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<strong>Molecular Genetics</strong>
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<p>In affected members of a large family with autosomal dominant CMYO4A previously reported by Laing et al. (1992), Laing et al. (1995) identified a heterozygous mutation in the TPM3 gene (M9R; 191030.0001) that segregated with the disorder. </p><p>In affected members of a French family with autosomal dominant CMYO4A, Penisson-Besnier et al. (2007) identified a heterozygous mutation in the TPM3 gene (R168H; 191030.0005). </p><p>Clarke et al. (2008) identified 5 different heterozygous TPM3 mutations (see, e.g., 191030.0005; 191030.0007; 191030.0008), in affected members of 6 unrelated families with CMYO4A and congenital fiber-type disproportion (CFTD) on skeletal muscle biopsy. The mutations were identified among 23 unrelated probands with CFTD, making mutations in the TPM3 gene the most common cause of CFTD to that time. </p><p>In a 38-year-old woman with CMYO4A associated with cap structures on skeletal muscle biopsy who had previously been reported by Fidzianska (2002), Ohlsson et al. (2009) identified a heterozygous mutation in the TPM3 gene (R168C; 191030.0009). </p><p>De Paula et al. (2009) reported a 42-year-old man with cap myopathy associated with a heterozygous de novo mutation in the TPM3 gene (R168H; 191030.0005). </p><p>Waddell et al. (2010) reported a man with CMYO4A and cap myopathy on skeletal muscle biopsy that was associated with a de novo heterozygous R168C mutation in the TPM3 gene. </p><p>Malfatti et al. (2013) reported a man of French Canadian origin with early-onset myopathy and a de novo heterozygous R168C mutation in the TPM3 gene. </p><p>In 2 affected members of a family with autosomal dominant CMYO4A, Schreckenbach et al. (2014) identified a heterozygous missense mutation in the TPM3 gene (L149I; 191030.0012). </p><p>Marttila et al. (2014) reported 11 unrelated families with CMYO4A due to heterozygous missense mutations in the TPM3 gene. Six novel heterozygous mutations and several recurrent mutations affecting codon 168 (R168C, R168H) were identified. </p><p>Xu et al. (2021) reported a 10-year-old Chinese girl with CMYO4A associated with a heterozygous R168G mutation in the TPM3 gene (R168G; 191030.0008) that was inherited from her clinically unaffected father. Her brother, who also carried the mutation, had a milder phenotype. The authors noted the intrafamilial variability. </p><p>In a 47-year-old man with CMYO4A, Bevilacqua et al. (2022) identified a heterozygous mutation in the TPM3 gene (E237K; 191030.0013). </p><p>Among 25 Brazilian families with a clinical diagnosis of nemaline myopathy, Gurgel-Giannetti et al. (2022) found 1 (4%) who carried a heterozygous missense mutation in the TPM3 gene (R168C; 191030.0009). The mutation was present in a father and son (family 7) with congenital myopathy, scoliosis, and nocturnal hypoventilation; both were ambulatory. The findings suggested that mutations in the TPM3 gene are not a common cause of nemaline myopathy. </p>
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<strong>Animal Model</strong>
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<p>Corbett et al. (2001) generated a transgenic mouse model expressing an autosomal dominant mutant of TPM3 (M9R; 191030.0001) previously identified in a human patient with nemaline myopathy. Rods were found in all muscles, but to varying extents which did not correlate with the amount of mutant protein present. In addition, a pathologic feature not commonly associated with this disorder, cytoplasmic bodies, was found in the mouse and subsequently identified in human samples. Hypertrophy of fast, type 2B (glycolytic) fibers was apparent at 2 months of age. Muscle weakness was apparent in mice at 5 to 6 months of age, mimicking the late onset observed in humans with this mutation. The onset of weakness correlated with an age-related decrease in fiber diameter and suggested that early onset may be prevented by hypertrophy of fast, glycolytic fibers. The authors suggested that the clinical phenotype may be precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness. </p>
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<strong>History</strong>
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<p>'Congenital fiber-type disproportion' (CFTD) myopathy is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. Clarke and North (2003) stated that the diagnosis of 'congenital fiber-type disproportion' as a disease entity is one of exclusion. They also suggested that the nonspecific histologic findings should be termed 'fiber size disproportion,' thus reserving the term CFTD for those cases in which no secondary cause can be found. </p><p>Brooke (1973) reported 12 cases and coined the term 'congenital fiber-type disproportion.' All patients had hypotrophy of type 1 muscle fibers, which were at least 12% smaller than either type 2A or type 2B fibers. Clinical features included congenital hypotonia, generalized weakness, and failure to thrive. Other features included long, thin face, scoliosis, high-arched palate, and multiple joint contractures. One patient had an affected parent.</p><p>Cavanagh et al. (1979) described 9 children with congenital fiber-type disproportion. Hypotonia, joint laxity, and congenital dislocation of the hip were the usual features. Muscle biopsies showed type 1 fibers that were smaller than the largest type 2 fibers by at least 13.5%. The natural history of the disorder was variable, with some children having fatal respiratory events. The parents in 1 case were second cousins. One mother was said to have weak legs in childhood, and another patient was said to have 2 affected paternal cousins. </p><p>Somer (1981) reported a 22-year-old man with muscle weakness and marfanoid features, including scoliosis. He had been a floppy infant. He worked as a television technician but could not lift TVs. Muscle biopsy showed type 1 fibers to be smaller than type 2 fibers. Type 2A fibers showed compensatory hypertrophy, and type 2B fibers were lacking.</p><p>Jaffe et al. (1988) described this disorder in a 12-year-old male and his infant sister. The parents were healthy and unrelated, suggesting autosomal recessive inheritance. </p><p>Clarke and North (2003) clarified the definition of CFTD through a comprehensive literature review and analysis. Of 218 reported cases of fiber size disproportion on muscle biopsy, they classified 67 cases as having CFTD, using inclusion criteria of (1) clinical muscle weakness and/or hypotonia, and (2) mean type 1 fiber diameter at least 12% smaller than mean type 2 fiber diameter. Exclusion criteria consisted of insufficient clinical information; a coexisting disorder of muscle or the nervous system; 2 or more syndromal features present; histologic features of a muscular dystrophy; and a coefficient of variation greater than 250 for type 2 fibers. In most cases, limb weakness was greatest in the limb girdle and proximal muscle groups, although many children had generalized muscle weakness. There was variable facial weakness (42% of patients), ophthalmoplegia (19%), and severe respiratory involvement (18%). Long face and high-arched palate were commonly reported. Reflexes were usually decreased or absent. Many patients had contractures, either at birth or developing later, of the ankles (10 cases), fingers (4 cases), hips (3 cases), elbows (3 cases), and knees (2 cases). Fifteen patients had scoliosis. Only 2 patients had cardiac involvement: dilated cardiomyopathy and atrial fibrillation, respectively (Banwell et al., 1999). Two patients had intellectual disability and 3 males had cryptorchidism. Fifty patients had type 1 fiber diameters that were 25% smaller than type 2, and these patients tended to have a more severe clinical phenotype. Family history was present in 43% of families, suggesting that genetics may play a role in a subset of patients. </p><p>Fardeau et al. (1975) reported a family with CFTD in which the father and 2 sisters were affected. </p><p>Curless and Nelson (1977) described this form of myopathy in identical twins. This occurrence in sibs and the parental consanguinity suggested autosomal recessive inheritance. Parental involvement pointing to an autosomal dominant mode of transmission for CFTD was reported by Kula et al. (1980) and Sulaiman et al. (1983). See also CFTDX (300580), which has been mapped to chromosome Xq13.1-q22.1. </p><p>Gerdes et al. (1994) reported a child with congenital fiber-type disproportion who was born with arthrogryposis multiplex congenita, dislocation of the hips, and mild scoliosis. By age 5 years, she had developed marked muscle weakness. Cytogenetic analysis identified a balanced chromosomal translocation, t(10;17)(p11.2;q25), transmitted by the clinically healthy mother. Maternal uniparental disomy for loci on either chromosome 10 or chromosome 17 was excluded. Although the mother had normal muscle strength and mass, muscle biopsy showed type 1 fiber predominance and EMG showed myopathic changes. Gerdes et al. (1994) suggested that congenital fiber-type disproportion in this family was dominantly inherited with variable expressivity, and that the translocation breakpoints may represent candidate gene regions. </p>
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<h4>
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<strong>See Also:</strong>
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</h4>
<span class="mim-text-font">
Brooke and Engel (1969)
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<strong>REFERENCES</strong>
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<ol>
<li>
<p class="mim-text-font">
Banwell, B. L., Becker, L. E., Jay, V., Taylor, G. P., Vajsar, J.
<strong>Cardiac manifestations of congenital fiber-type disproportion myopathy.</strong>
J. Child Neurol. 14: 83-87, 1999.
[PubMed: 10073429]
[Full Text: https://doi.org/10.1177/088307389901400205]
</p>
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<li>
<p class="mim-text-font">
Bevilacqua, J. A., Contreras, J. P., Trangulao, A., Hernandez, U., Brochier, G., Diaz, J., Hughes, R., Campero, M., Romero, N. B.
<strong>Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern.</strong>
Neuromusc. Disord. 32: 687-691, 2022.
[PubMed: 35688744]
[Full Text: https://doi.org/10.1016/j.nmd.2022.05.014]
</p>
</li>
<li>
<p class="mim-text-font">
Brooke, M. H., Engel, W. K.
<strong>The histographic analysis of human muscle biopsies with regard to fibre types. IV. Children&#x27;s biopsies.</strong>
Neurology 19: 591-605, 1969.
[PubMed: 5814304]
[Full Text: https://doi.org/10.1212/wnl.19.6.591]
</p>
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<li>
<p class="mim-text-font">
Brooke, M. H.
<strong>Congenital fiber type disproportion. In: Kakulas, B. A.: Clinical Studies in Myology. Proc. of the 2nd Int. Cong. on Muscle Diseases, Perth, Australia, 1971. Part 2.</strong>
Amsterdam: Excerpta Medica (pub.) 1973. Pp. 147-159.
</p>
</li>
<li>
<p class="mim-text-font">
Cavanagh, N. P., Lake, B. D., McMeniman, P.
<strong>Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.</strong>
Arch. Dis. Child. 54: 735-743, 1979.
[PubMed: 507896]
[Full Text: https://doi.org/10.1136/adc.54.10.735]
</p>
</li>
<li>
<p class="mim-text-font">
Clarke, N. F., Kolski, H., Dye, D. E., Lim, E., Smith, R. L. L., Patel, R., Fahey, M. C., Bellance, R., Romero, N. B., Johnson, E. S., Labarre-Vila, A., Monnier, N., Laing, N. G., North, K. N.
<strong>Mutations in TPM3 are a common cause of congenital fiber type disproportion.</strong>
Ann. Neurol. 63: 329-337, 2008.
[PubMed: 18300303]
[Full Text: https://doi.org/10.1002/ana.21308]
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<p class="mim-text-font">
Clarke, N. F., North, K. N.
<strong>Congenital fiber type disproportion--30 years on.</strong>
J. Neuropath. Exp. Neurol. 62: 977-989, 2003.
[PubMed: 14575234]
[Full Text: https://doi.org/10.1093/jnen/62.10.977]
</p>
</li>
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<p class="mim-text-font">
Corbett, M. A., Robinson, C. S., Dunglison, G. F., Yang, N., Joya, J. E., Stewart, A. W., Schnell, C., Gunning, P. W., North, K. N., Hardeman, E. C.
<strong>A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy.</strong>
Hum. Molec. Genet. 10: 317-328, 2001.
[PubMed: 11157795]
[Full Text: https://doi.org/10.1093/hmg/10.4.317]
</p>
</li>
<li>
<p class="mim-text-font">
Curless, R. G., Nelson, M. B.
<strong>Congenital fiber type disproportion in identical twins.</strong>
Ann. Neurol. 2: 455-459, 1977.
[PubMed: 569460]
[Full Text: https://doi.org/10.1002/ana.410020603]
</p>
</li>
<li>
<p class="mim-text-font">
De Paula, A. M., Franques, J., Fernandez, C., Monnier, N., Lunardi, J., Pellissier, J.-F., Figarella-Branger, D., Pouget, J.
<strong>A TPM3 mutation causing cap myopathy.</strong>
Neuromusc. Disord. 19: 685-688, 2009.
[PubMed: 19553118]
[Full Text: https://doi.org/10.1016/j.nmd.2009.06.365]
</p>
</li>
<li>
<p class="mim-text-font">
Donkervoort, S., Papadaki, M., de Winter, J. M., Neu, M. B., Kirschner, J., Bolduc, V., Yang, M. L., Gibbons, M. A., Hu, Y., Dastgir, J., Leach, M. E., Rutkowski, A., and 11 others.
<strong>TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.</strong>
Ann. Neurol. 78: 982-994, 2015.
[PubMed: 26418456]
[Full Text: https://doi.org/10.1002/ana.24535]
</p>
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<li>
<p class="mim-text-font">
Fardeau, M., Harpey, J. P., Caille, B.
<strong>Disproportion congenitale des differents types de fibre musculaire, avec petitesse relative des fibres de type I: documents morphologiques concernant les biopsies musculaires prelevees chez trois membres d&#x27;une meme famille.</strong>
Rev. Neurol. 131: 745-766, 1975.
[PubMed: 130671]
</p>
</li>
<li>
<p class="mim-text-font">
Fidzianska, A.
<strong>&#x27;Cap disease&#x27;--a failure in the correct muscle fibre formation.</strong>
J. Neurol. Sci. 201: 27-31, 2002.
[PubMed: 12163190]
[Full Text: https://doi.org/10.1016/s0022-510x(02)00156-9]
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</li>
<li>
<p class="mim-text-font">
Gerdes, A. M., Petersen, M. B., Schroder, H. D., Wulff, K., Brondum-Nielsen, K.
<strong>Congenital myopathy with fiber type disproportion: a family with a chromosomal translocation t(10;17) may indicate candidate gene regions.</strong>
Clin. Genet. 45: 11-16, 1994.
[PubMed: 7908614]
[Full Text: https://doi.org/10.1111/j.1399-0004.1994.tb03982.x]
</p>
</li>
<li>
<p class="mim-text-font">
Gurgel-Giannetti, J., Souza, L. S., Yamamoto, G. L., Belisario, M., Lazar, M., Campos, W., Pavanello, R. C. M., Zatz, M., Reed, U., Zanoteli, E., Oliveira, A. B., Lehtokari, V.-L., Casella, E. B., Machado-Costa, M. C., Wallgren-Pettersson, C., Laing, N. G., Nigro, V., Vainzof, M.
<strong>Nemaline myopathy in Brazilian patients: molecular and clinical characterization.</strong>
Int. J. Molec. Sci. 23: 11995, 2022.
[PubMed: 36233295]
[Full Text: https://doi.org/10.3390/ijms231911995]
</p>
</li>
<li>
<p class="mim-text-font">
Jaffe, M., Shapira, J., Borochowitz, Z.
<strong>Familial congenital fiber type disproportion (CFTD) with an autosomal recessive inheritance.</strong>
Clin. Genet. 33: 33-37, 1988.
[PubMed: 3342545]
[Full Text: https://doi.org/10.1111/j.1399-0004.1988.tb04261.x]
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<li>
<p class="mim-text-font">
Kula, R. W., Sher, J. H., Shafiq, S. A., Hardy-Stashin, J.
<strong>Variability of clinical pathological manifestations in familial fiber type disproportion.</strong>
Trans. Am. Neurol. Assoc. 105: 416-418, 1980.
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<li>
<p class="mim-text-font">
Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A.
<strong>Assignment of nemaline myopathy (MIM 161800, NEM1) to chromosome 1. (Abstract)</strong>
Cytogenet. Cell Genet. 58: 1858, 1991.
</p>
</li>
<li>
<p class="mim-text-font">
Laing, N. G., Majda, B. T., Akkari, P. A., Layton, M. G., Mulley, J. C., Phillips, H., Haan, E. A., White, S. J., Beggs, A. H., Kunkel, L. M., Groth, D. M., Boundy, K. L., Kneebone, C. S., Blumbergs, P. C., Wilton, S. D., Speer, M. C., Kakulas, B. A.
<strong>Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1.</strong>
Am. J. Hum. Genet. 50: 576-583, 1992.
[PubMed: 1347195]
</p>
</li>
<li>
<p class="mim-text-font">
Laing, N. G., Wilton, S. D., Akkari, P. A., Dorosz, S., Boundy, K., Kneebone, C., Blumbergs, P., White, S., Watkins, H., Love, D. R., Haan, E.
<strong>A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.</strong>
Nature Genet. 9: 75-79, 1995. Note: Erratum: Nature Genet. 10: 249 only, 1995.
[PubMed: 7704029]
[Full Text: https://doi.org/10.1038/ng0195-75]
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<li>
<p class="mim-text-font">
Malfatti, E., Schaeffer, U., Chapon, F., Yang, Y., Eymard, B., Xu, R., Laporte, J., Romero, N. B.
<strong>Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene.</strong>
Neuromusc. Disord. 23: 992-997, 2013.
[PubMed: 24095155]
[Full Text: https://doi.org/10.1016/j.nmd.2013.07.003]
</p>
</li>
<li>
<p class="mim-text-font">
Marttila, M., Lehtokari, V.-L., Marston, S., Nyman, T. A., Barnerias, C., Beggs, A. H., Bertini, E., Ceyhan-Birsoy, O., Cintas, P., Gerard, M., Gilbert-Dussardier, B., Hogue, J. S., and 29 others.
<strong>Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies.</strong>
Hum. Mutat. 35: 779-790, 2014.
[PubMed: 24692096]
[Full Text: https://doi.org/10.1002/humu.22554]
</p>
</li>
<li>
<p class="mim-text-font">
Ohlsson, M., Fidzianska, A., Tajsharghi, H., Oldfors, A.
<strong>TPM3 mutation in one of the original cases of cap disease.</strong>
Neurology 72: 1961-1963, 2009.
[PubMed: 19487656]
[Full Text: https://doi.org/10.1212/WNL.0b013e3181a82659]
</p>
</li>
<li>
<p class="mim-text-font">
Penisson-Besnier, I., Monnier, N., Toutain, A., Dubas, F., Laing, N.
<strong>A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.</strong>
Neuromusc. Disord. 17: 330-337, 2007.
[PubMed: 17376686]
[Full Text: https://doi.org/10.1016/j.nmd.2007.01.017]
</p>
</li>
<li>
<p class="mim-text-font">
Schreckenbach, T., Schroder, J. M., Voit, T., Abicht, A., Neuen-Jacob, E., Roos, A., Bulst, S., Kuhl, C., Schulz, J. B., Weis, J., Claeys, K. G.
<strong>Novel TPM3 mutation in a family with cap myopathy and review of the literature.</strong>
Neuromusc. Disord. 24: 117-124, 2014.
[PubMed: 24239060]
[Full Text: https://doi.org/10.1016/j.nmd.2013.10.002]
</p>
</li>
<li>
<p class="mim-text-font">
Serratrice, G., Pellissier, J. F., Gastaut, J. L., Pouget, J.
<strong>Congenital myopathy with selective hypotrophy of type I fibers.</strong>
Rev. Neurol. (Paris) 131: 813-816, 1975.
[PubMed: 1221488]
</p>
</li>
<li>
<p class="mim-text-font">
Somer, M.
<strong>Personal Communication.</strong>
Helsinki, Finland 5/27/1981.
</p>
</li>
<li>
<p class="mim-text-font">
Sulaiman, A., Swick, H. M., Kinder, D. S.
<strong>Congenital fibre type disproportion with unusual clinico-pathologic manifestations.</strong>
J. Neurol. Neurosurg. Psychiat. 46: 175-182, 1983.
[PubMed: 6842223]
[Full Text: https://doi.org/10.1136/jnnp.46.2.175]
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</li>
<li>
<p class="mim-text-font">
Waddell, L. B., Kreissl, M., Kornberg, A., Kennedy, P., McLean, C., Labarre-Vila, A., Monnier, N., North, K. N., Clarke, N. F.
<strong>Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.</strong>
Neuromusc. Disord. 20: 464-466, 2010.
[PubMed: 20554445]
[Full Text: https://doi.org/10.1016/j.nmd.2010.05.012]
</p>
</li>
<li>
<p class="mim-text-font">
Xu, H., Liu, H., Chen, T., Song, B., Zhu, J., Liu, X., Li, M., Luo, C.
<strong>The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications.</strong>
Genes Dis. 8: 715-720, 2021.
[PubMed: 34291143]
[Full Text: https://doi.org/10.1016/j.gendis.2020.01.010]
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Cassandra L. Kniffin - updated : 06/01/2023<br>Cassandra L. Kniffin - updated : 03/05/2023<br>Cassandra L. Kniffin - updated : 9/28/2009<br>Cassandra L. Kniffin - updated : 12/28/2007<br>Cassandra L. Kniffin - updated : 9/18/2007<br>Cassandra L. Kniffin - updated : 5/3/2006<br>Cassandra L. Kniffin - updated : 3/14/2006<br>Cassandra L. Kniffin - reorganized : 7/13/2005<br>Cassandra L. Kniffin - updated : 7/1/2005<br>Victor A. McKusick - updated : 1/8/2003
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