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Entry
- #272430 - CRISPONI/COLD-INDUCED SWEATING SYNDROME 1; CISS1
- OMIM
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<span class="h4">#272430</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/272430"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS272430"> <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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<a href="#nomenclature">Nomenclature</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<div><a href="https://clinicaltrials.gov/search?cond=CRISPONI/COLD-INDUCED SWEATING SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1701&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Crisponi syndrome&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=17149&Typ=Pat" title="Cold-induced sweating syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Cold-induced sweating synd…&nbsp;</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Crisponi syndrome</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157820" title="Cold-induced sweating syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Cold-induced sweating synd…</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/82e39953-2b03-449d-9a76-59f7c60e37a6/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0080329" 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/272430" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
</div>
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</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.">
&nbsp;
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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> 702363009, 725097006<br />
<strong>ORPHA:</strong> 1545, 157820<br />
<strong>DO:</strong> 0080329<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
272430
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
CRISPONI/COLD-INDUCED SWEATING SYNDROME 1; CISS1
</span>
</h3>
</div>
<div>
<br />
</div>
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<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
CRISPONI SYNDROME<br />
SOHAR-CRISPONI SYNDROME<br />
MUSCLE CONTRACTIONS, TETANOFORM, WITH CHARACTERISTIC FACE, CAMPTODACTYLY, HYPERTHERMIA, AND SUDDEN DEATH
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/470?start=-3&limit=10&highlight=470">
19p13.11
</a>
</span>
</td>
<td>
<span class="mim-font">
Cold-induced sweating syndrome 1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/272430"> 272430 </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">
CRLF1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/604237"> 604237 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
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<a href="/clinicalSynopsis/272430" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
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<a href="/phenotypicSeries/PS272430" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/272430" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/272430" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Poor growth in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550715&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550715</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">
- Severe contractions of the facial muscles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748650&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748650</a>]</span><br /> -
Facial trismus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748651&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748651</a>]</span><br /> -
Large face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748652&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748652</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100729</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100729</a>]</span><br /> -
Chubby cheeks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748653&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748653</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span><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 /> -
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 /> -
Facial weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95666008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95666008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R29.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R29.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.83</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/781.94" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.94</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427055</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007209" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007209</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030319" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030319</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low-set ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95515009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95515009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q17.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q17.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239234&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239234</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000369</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ear,Low-Set-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=9f0956aaa4fd45c34f94336afbbdc931&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">
- Chronic keratitis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550716&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550716</a>]</span><br /> -
Inability to fully close eyes during sleep <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550717&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550717</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Depressed nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17&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 /> -
Broad nose <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249321001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249321001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000445" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000445</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000445" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000445</a>]</span><br /> -
Anteverted nostrils <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/708670007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">708670007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span><br /> -
Long philtrum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865014&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865014</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000343" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000343</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Philtrum,Long-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6e8169f9668cf95ffe7aad93a28f672b&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 /> -
Abundant salivation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748654</a>]</span><br /> -
Small mouth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14582003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14582003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q18.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q18.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/744.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">744.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000160</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000160" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000160</a>]</span><br /> -
Dental caries, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851048&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851048</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80967001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80967001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K02</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K02.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K02.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/521.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">521.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/521.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">521.00</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000670" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000670</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 hypertonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748655&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748655</a>]</span><br /> -
Short neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95427009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95427009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Neck,Short-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531&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>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Dyspnea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267036007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267036007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230145002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230145002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.02</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.05" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.05</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013404&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013404</a>, <a href="https://bioportal.bioontology.org/search?q=C2024878&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2024878</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002094" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002094</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002094" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002094</a>]</span><br /> -
Apneic spells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806434&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806434</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Feeding difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<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 /> -
Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Elbow contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/239734000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">239734000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.52</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034391" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034391</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Camptodactyly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29271008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29271008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221369</a>, <a href="https://bioportal.bioontology.org/search?q=C0685409&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0685409</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012385" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012385</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012385" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012385</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=56cd131f7e4abed85662f1f7e23b10a2" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Camptodactyly-large-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=56cd131f7e4abed85662f1f7e23b10a2&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 /> -
Tapered fingers <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249768009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249768009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001182" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001182</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001182" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001182</a>]</span><br /> -
Ulnar deviation of the fingers <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1293023007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1293023007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367510009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367510009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0231679&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0231679</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009465" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009465</a>]</span><br /> -
Adducted thumbs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205273005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205273005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001181</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001181</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">
- Club feet <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Profuse sweating of the upper body induced by cold exposure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550719&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550719</a>]</span><br /> -
Poor sweating in response to heat <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550720&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550720</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">
- Generalized muscle contractions, episodic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806552</a>]</span><br /> -
Tetanus-like muscle contractions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748657&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748657</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">
- Seizures (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Opisthotonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8652009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8652009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002179</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002179</a>]</span><br /> -
Mental retardation (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Subcortical white matter abnormalities seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550714&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550714</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">
- Decreased pain sensitivity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866932&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866932</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> VOICE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Nasal voice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/289190003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">289190003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0566620&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0566620</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001611</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001611" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001611</a>]</span><br />
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<strong> METABOLIC FEATURES </strong>
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- Variable fever <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2748661&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2748661</a>]</span><br /> -
Hyperthermia, episodic <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77957000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77957000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/A68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714772</a>, <a href="https://bioportal.bioontology.org/search?q=C0277799&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0277799</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.60</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Onset in early infancy<br /> -
High early mortality rate if untreated<br /> -
Muscle contractions in infancy occur in response to tactile stimulation or crying<br /> -
Fever, muscle cramping, and poor feeding remit by age 2 years<br /> -
Cold-induced sweating develops late in the first decade<br /> -
Clonidine can alleviate hyperhidrosis<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the cytokine-like factor 1 gene (CRLF1, <a href="/entry/604237#0001">604237.0001</a>)<br />
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Cold-induced sweating syndrome
- <a href="/phenotypicSeries/PS272430">PS272430</a>
- 3 Entries
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<strong>Phenotype</strong>
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<strong>Gene/Locus</strong>
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<a href="/geneMap/7/111?start=-3&limit=10&highlight=111"> 7p15.3 </a>
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<a href="/entry/617055"> PERCHING syndrome </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/617055"> 617055 </a>
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<a href="/entry/611119"> KLHL7 </a>
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<a href="/entry/611119"> 611119 </a>
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<a href="/geneMap/11/658?start=-3&limit=10&highlight=658"> 11q13.2 </a>
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<a href="/entry/610313"> Cold-induced sweating syndrome 2 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/610313"> 610313 </a>
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<a href="/entry/607672"> CLCF1 </a>
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<a href="/entry/607672"> 607672 </a>
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<a href="/geneMap/19/470?start=-3&limit=10&highlight=470"> 19p13.11 </a>
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<a href="/entry/272430"> Cold-induced sweating syndrome 1 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/272430"> 272430 </a>
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<a href="/entry/604237"> CRLF1 </a>
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<a href="/entry/604237"> 604237 </a>
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Crisponi/cold-induced sweating syndrome-1 (CISS1) is caused by homozygous or compound heterozygous mutation in the CRLF1 gene (<a href="/entry/604237">604237</a>) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Crisponi/cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis (summary by <a href="#6" class="mim-tip-reference" title="Hahn, A. F., Waaler, P. E., Kvistad, P. H., Bamforth, J. S., Miles, J. H., McLeod, J. G., Knappskog, P. M., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood: four new cases.&lt;/strong&gt; J. Neurol. Sci. 293: 68-75, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20400119/&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;20400119&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jns.2010.02.028&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="20400119">Hahn et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20400119" 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="Buers, I., Persico, I., Schoning, L., Nitschke, Y., Di Rocco, M., Loi, A., Sahi, P. K., Utine, G. E., Bayraktar-Tanyeri, B., Zampino, G., Cripsoni, G., Rutsch, F., Crisponi, L. &lt;strong&gt;Crisponi-cold-induced sweating syndrome: differential diagnosis, pathogenesis and treatment concepts.&lt;/strong&gt; Clin. Genet. 97: 209-221, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31497877/&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;31497877&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/cge.13639&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="31497877">Buers et al. (2020)</a> provided a detailed review of Crisponi/CISS, including clinical features, diagnosis, and evolution of the disease, differential diagnosis, pathogenesis, and recommended management and treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31497877" 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>Genetic Heterogeneity of Crisponi/Cold-Induced Sweating Syndrome</em></strong></p><p>
Crisponi/cold-induced sweating syndrome-2 (CISS2; <a href="/entry/610313">610313</a>), which is clinically indistinguishable from CISS1, is caused by mutation in the CLCF1 gene (<a href="/entry/607672">607672</a>) on chromosome 11q13.</p>
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<p><a href="#11" class="mim-tip-reference" title="Sohar, E., Schoenfeld, Y., Udassin, R., Magazanik, A., Revach, M. &lt;strong&gt;Cold-induced profuse sweating on back and chest: a new genetic entity?&lt;/strong&gt; Lancet 312: 1073-1074, 1978. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/82089/&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;82089&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(78)91805-6&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="82089">Sohar et al. (1978)</a> first described cold-induced sweating syndrome, and <a href="#3" class="mim-tip-reference" title="Crisponi, G. &lt;strong&gt;Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?&lt;/strong&gt; Am. J. Med. Genet. 62: 365-371, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8723066/&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;8723066&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q&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="8723066">Crisponi (1996)</a> first described a disorder in infancy that was characterized by muscular contraction of the facial muscles, poor feeding, and episodic fever, often resulting in early death. Both conditions were found to be due to mutation in the same gene. Moreover, it became apparent that most older patients with CISS have a history of features consistent with Crisponi syndrome early in life, indicating that these 2 disorders represent a single entity with variable severity and/or different manifestations according to age. <a href="#7" class="mim-tip-reference" title="Herholz, J., Meloni, A., Marongiu, M., Chiappe, F., Deiana, M., Herrero, C. R., Zampino, G., Hamamy, H., Zalloum, Y., Waaler, P. E., Crisponi, G., Crisponi, L., Rutsch, F. &lt;strong&gt;Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.&lt;/strong&gt; Europ. J. Hum. Genet. 19: 525-533, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21326283/&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;21326283&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21326283[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/10.1038/ejhg.2010.253&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="21326283">Herholz et al. (2011)</a> suggested the term 'Sohar-Crisponi syndrome' to refer to the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8723066+82089+21326283" 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="#11" class="mim-tip-reference" title="Sohar, E., Schoenfeld, Y., Udassin, R., Magazanik, A., Revach, M. &lt;strong&gt;Cold-induced profuse sweating on back and chest: a new genetic entity?&lt;/strong&gt; Lancet 312: 1073-1074, 1978. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/82089/&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;82089&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(78)91805-6&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="82089">Sohar et al. (1978)</a> observed 2 Israeli sisters who, since childhood, sweated profusely from the back and chest when exposed to temperatures of 7 to 18 degrees C. They also showed high palate, inability to extend the elbows fully, and slight kyphoscoliosis--features demonstrated by neither the parents nor the sibs. The parents shared a grandfather, i.e., were half first cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=82089" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.&lt;/strong&gt; Am. J. Hum. Genet. 72: 375-383, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12509788/&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;12509788&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/346120&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="12509788">Knappskog et al. (2003)</a> observed 2 Norwegian brothers with a clinical phenotype similar to that in the Israeli sisters. The disorder in the brothers was more severe than that in the Israeli sisters, with earlier age of onset, feeding difficulties, serious kyphoscoliosis, and reduced pain and temperature sensitivity. The older brother would not suckle in the neonatal period, leading to dehydration. He was fed first by a nasogastric tube and subsequently by a special sucking device intended for newborn lambs. These feeding problems, complicated by bronchopulmonary and urinary tract infections, led to hospitalization for his first 3 months of life. His younger brother was admitted at 1 day of age, primarily because of respiratory problems. He too did not suckle spontaneously and had to be fed in the same manner as his older brother. Both had difficulty fully opening their mouths. While playing in the snow, the older brother repeatedly experienced frostbite in his hands. Furthermore, he could hold his palms in a flame or put his hands in boiling water without any sensory pain. Both brothers had severe progressive kyphoscoliosis requiring extensive surgery, following which the boys had an unusually low requirement for pain-relieving medication. Both brothers had short hands with pronounced clinodactyly and tapering of fingers. They could not fully extend their elbows. Their sweating problem was noted at the age of approximately 7 years. The patchwise distribution in affected areas closely resembled those described in the Israeli sisters. These areas did not sweat at warm temperatures, during fever episodes, or during exercise. The mother sometimes had to cool her overheated children by putting their feet in cold water. Subtropical environment did not bother these patients. They could stay in bright sunlight without feeling the heat and had no desire to take their clothes off for cooling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Crisponi, G. &lt;strong&gt;Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?&lt;/strong&gt; Am. J. Med. Genet. 62: 365-371, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8723066/&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;8723066&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q&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="8723066">Crisponi (1996)</a> described an autosomal recessive syndrome observed in 17 newborns (8 males, 9 females) from 12 different families in southern Sardinia. The disorder was evident at birth and was characterized by marked muscular contraction of the facial muscles in response to tactile stimuli or during crying, with trismus and abundant salivation simulating a tetanic spasm. The contractions slowly disappear as the infant calms. There is also neck muscle hypertonia with a tendency to opisthotonos. All patients presented facial anomalies such as large face, chubby cheeks, broad nose with anteverted nostrils, and long philtrum, and showed bilateral camptodactyly. The clinical course in all patients had been characterized by marked feeding difficulties and appearance of variable fever at about 38 degrees centigrade, with peaks of irregular hyperthermia of over 42 degrees centigrade, with onset ranging from birth to a few weeks. In some patients generalized seizures occurred. Death occurred after a period of a few weeks to some months and coincided with fever about 42 degrees centigrade. <a href="#3" class="mim-tip-reference" title="Crisponi, G. &lt;strong&gt;Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?&lt;/strong&gt; Am. J. Med. Genet. 62: 365-371, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8723066/&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;8723066&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q&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="8723066">Crisponi (1996)</a> stated that no useful pathogenetic features were revealed by laboratory investigations. Only 2 patients were alive at the time of report. One patient (aged 14 years) presented slow regression of the dystonic features, while dysthermia and mild psychomotor delay persisted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Accorsi, P., Giordano, L., Faravelli, F. &lt;strong&gt;Crisponi syndrome: report of a further patient.&lt;/strong&gt; Am. J. Med. Genet. 123A: 183-185, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14598344/&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;14598344&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20292&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="14598344">Accorsi et al. (2003)</a> reported a patient with features consistent with Crisponi syndrome. The patient was born of unrelated parents, but both parents came from a small village in a geographically isolated area in northern Italy with a high rate of inbreeding. The pregnancy was complicated by polyhydramnios, and unspecified fetal hand abnormalities were noted by ultrasound. Dysmorphic features were noted at birth, including hypomimic, rounded face, puffy cheeks, broad nose with anteverted nostrils, small mouth with thin and contracted lips, micrognathia, low-set ears, low anterior and posterior hairlines, and a short neck. The hands showed bilateral camptodactyly with ulnar deviation of the fingers and adducted thumbs. The patient exhibited episodes of marked contraction of both facial and neck muscles associated with flexion of the upper limbs, clenching of the hands, and hyperextension of the lower limbs. During these episodes, there was abundant salivation with inability to swallow. Respiratory muscle contractions caused dyspnea, cyanosis, and short apneic spells. The episodes were elicited by crying and by tactile or painful sensation; they did not occur during rest or sleep. At 2 months of age, the patient developed intermittent hyperthermia with fever peaks and rapid falls unassociated with infection. These hyperthermic episodes were followed by hypernatremic dehydration and acute renal failure. The child died at age 4 months of cardiorespiratory failure following a hyperthermic crisis. Skeletal radiography showed mild anomalies and scoliosis. Karyotype analysis identified a pericentric inversion of the heterochromatic region of chromosome 9 of paternal origin. <a href="#1" class="mim-tip-reference" title="Accorsi, P., Giordano, L., Faravelli, F. &lt;strong&gt;Crisponi syndrome: report of a further patient.&lt;/strong&gt; Am. J. Med. Genet. 123A: 183-185, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14598344/&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;14598344&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20292&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="14598344">Accorsi et al. (2003)</a> noted the phenotypic similarities to Freeman-Sheldon syndrome (<a href="/entry/193700">193700</a>) and Stuve-Wiedemann syndrome (<a href="/entry/601559">601559</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14598344" 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="Nannenberg, E. A., Bijlmer, R., Van Geel, B. M., Hennekam, R. C. M. &lt;strong&gt;Neonatal paroxysmal trismus and camptodactyly: the Crisponi syndrome.&lt;/strong&gt; Am. J. Med. Genet. 133A: 90-92, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15637710/&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;15637710&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30536&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="15637710">Nannenberg et al. (2005)</a> reported a 4-year-old boy of Portuguese descent with Crisponi syndrome. Four days after birth, the infant was noted to have bouts of generalized muscle contractions occurring 6 to 10 times per day. The attacks were triggered by external stimuli and involved contraction of the facial muscles, clenching of the hands, jerky movements of the legs, and respiratory abnormalities. The attacks also occurred during sleep. Facial features included round face, broad nose with anteverted nostrils, small mouth, high-arched palate, micrognathia, and retroversion of the ears. He had bilateral camptodactyly and clubfeet. Polysomnography during a paroxysmal event showed a severe obstructive breathing pattern. The overall breathing pattern outside the attacks showed a mix of disorders of control of breathing, including central apnea, hypopnea, obstructive apnea, and long periods of expiratory apneas while the boy was awake. The hyperexcitability disappeared in the course of the first year of life. As he grew older, he developed scoliosis and showed severely delayed psychomotor development. Hyperthermia was never recorded. <a href="#9" class="mim-tip-reference" title="Nannenberg, E. A., Bijlmer, R., Van Geel, B. M., Hennekam, R. C. M. &lt;strong&gt;Neonatal paroxysmal trismus and camptodactyly: the Crisponi syndrome.&lt;/strong&gt; Am. J. Med. Genet. 133A: 90-92, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15637710/&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;15637710&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30536&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="15637710">Nannenberg et al. (2005)</a> noted the similarities to Stuve-Wiedemann syndrome, but concluded that Crisponi syndrome is a unique entity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637710" 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>Following up on one of the surviving patients of <a href="#3" class="mim-tip-reference" title="Crisponi, G. &lt;strong&gt;Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?&lt;/strong&gt; Am. J. Med. Genet. 62: 365-371, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8723066/&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;8723066&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q&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="8723066">Crisponi (1996)</a>, <a href="#5" class="mim-tip-reference" title="Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V. &lt;strong&gt;Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 80: 966-970, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436251/&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;17436251&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436251[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/513608&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="17436251">Dagoneau et al. (2007)</a> noted that she developed scoliosis, which required surgery at age 12 years, and mild developmental delay with attention deficit disorder, requiring special schooling. At age 13 years, growth parameters were at less than -2 SD. See <a href="/entry/604237#0003">604237.0003</a>. <a href="#5" class="mim-tip-reference" title="Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V. &lt;strong&gt;Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 80: 966-970, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436251/&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;17436251&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436251[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/513608&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="17436251">Dagoneau et al. (2007)</a> also described 2 cousins from a Gypsy family with Crisponi syndrome. One of the patients presented at birth with camptodactyly, overlapping toes, joint contractures of elbows, contractions of facial muscles with trismus, major feeding difficulties, and dysmorphic features (small nose with anteverted nostrils, small mouth, short neck, and low-set ears). He had repeated episodes of hyperthermia (body temperature greater than 42 degrees centigrade) until age 3 years and then profuse sweating of the back. Kyphoscoliosis appeared at age 1 year. At the time of the report, he was 6 years old; growth parameters were at -2 SD, and he had some speech delay. His first cousin also presented with facial muscle contractions, camptodactyly, elbow contractures, and feeding difficulties, and he developed seizures and temperature instability with access of hyperthermia and kyphoscoliosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8723066+17436251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Thomas, N., Danda, S., Kumar, M., Jana, A. K., Crisponi, G., Meloni, A., Crisponi, L. &lt;strong&gt;Crisponi syndrome in an Indian patient: a rare differential diagnosis for neonatal tetanus.&lt;/strong&gt; Am. J. Med. Genet. 146A: 2831-2834, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18837055/&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;18837055&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32487&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="18837055">Thomas et al. (2008)</a> reported an Indian boy, born of consanguineous parents, with Crisponi syndrome. He presented with respiratory distress soon after birth and was noted to have sparse light hair, upslanting eyes, blepharophimosis, broad nose with anteverted nares, long philtrum, retrognathia, and bilateral camptodactyly. He developed tetanus-like spasms on the second day of life characterized by marked contraction of all the muscles, particularly the facial muscles, with trismus, excess salivation, and opisthotonus. Cyanosis and apnea requiring oxygen were present during some of these episodes. He also had episodes of hyperthermia. At 10 months of age, he was still having feeding problems, remained hypertonic with intermittent spasms, and was developmentally delayed. Genetic analysis identified a homozygous 5-kb deletion surrounding exon 1 of the CRLF1 gene. <a href="#13" class="mim-tip-reference" title="Thomas, N., Danda, S., Kumar, M., Jana, A. K., Crisponi, G., Meloni, A., Crisponi, L. &lt;strong&gt;Crisponi syndrome in an Indian patient: a rare differential diagnosis for neonatal tetanus.&lt;/strong&gt; Am. J. Med. Genet. 146A: 2831-2834, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18837055/&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;18837055&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32487&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="18837055">Thomas et al. (2008)</a> emphasized that the dysmorphic features aided in the correct diagnosis, which would otherwise have been considered to be neonatal tetanus. The authors also noted that since the CRLF1 gene is involved in motor neuron survival and in the function of the autonomic nervous system, Crisponi syndrome is characterized by dysautonomic symptoms including disturbances in temperature regulation and neonatal feeding/swallowing, as well as respiratory trismus, facial spasms, and paradoxical sweating. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18837055" 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="Okur, I., Tumer, L., Crisponi, L., Eminoglu, F. T., Chiappe, F., Cinaz, P., Yenicesu, I., Hasanoglu, A. &lt;strong&gt;Crisponi syndrome: a new case with additional features and new mutation in CRLF1. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 146A: 3237-3239, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19012339/&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;19012339&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32531&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="19012339">Okur et al. (2008)</a> reported a 9-month-old boy of Turkish descent with typical features of Crisponi syndrome who also had velopharyngeal insufficiency, incomplete cleft palate, and thin corpus callosum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19012339" 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="#15" class="mim-tip-reference" title="Yamazaki, M., Kosho, T., Kawachi, S., Mikoshiba, M., Takahashi, J., Sano, R., Oka, K., Yoshida, K., Watanabe, T., Kato, H., Komatsu, M., Kawamura, R., Wakui, K., Knappskog, P. M., Boman, H., Fukushima, Y. &lt;strong&gt;Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation.&lt;/strong&gt; Am. J. Med. Genet. 152A: 764-769, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20186812/&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;20186812&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33315&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="20186812">Yamazaki et al. (2010)</a> reported a 30-year-old Japanese woman, born of consanguineous parents, with CISS1 confirmed by molecular studies. After birth, she showed poor feeding, flexion contractures of the fingers, scoliosis, and recurrent episodes of fever. Notable facial features included large face with thick and arched eyebrows, short nose with anteverted nostrils, full cheeks, and small mouth. Later in childhood, she developed profuse cold-induced sweating as well as decreased sensitivity to pain. She also had severe dental caries requiring complete tooth extraction. Examination at age 30 showed a marfanoid habitus, dolichocephaly, slender face with poor expression, narrow nose, malar hypoplasia, prognathism, and small mouth. Neurologic examination showed hyporeflexia of the upper extremities, and brain MRI showed multiple high-intensity spots on the subcortical white matter of the frontal lobes. She also had camptodactyly with finger joint malalignment and kyphoscoliosis. The longitudinal data from this patient suggested that CISS and Crisponi syndrome are one clinical entity with variable clinical expression or different phenotypic stages according to age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186812" 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="Hahn, A. F., Waaler, P. E., Kvistad, P. H., Bamforth, J. S., Miles, J. H., McLeod, J. G., Knappskog, P. M., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood: four new cases.&lt;/strong&gt; J. Neurol. Sci. 293: 68-75, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20400119/&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;20400119&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jns.2010.02.028&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="20400119">Hahn et al. (2010)</a> reported 2 unrelated patients with CISS1. A 24-year-old woman had features of Crisponi syndrome in infancy, including poor feeding, facial muscle contractions, opisthotonus posturing when handled, tight jaw and inability to open the mouth fully, high-arched palate, micrognathia, elbow contractures, and camptodactyly. She could not tolerate summer heat and showed profuse cold-induced sweating of the upper body. She had normal psychomotor development. Later, she developed progressive scoliosis and severe dental decay. Treatment with clonidine alleviated the hyperhidrosis. A 19-year-old Norwegian man had similar features, but was also noted to have decreased pain perception and chronic exposure keratitis due to an inability to close his eyes fully during sleep. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20400119" 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="Herholz, J., Meloni, A., Marongiu, M., Chiappe, F., Deiana, M., Herrero, C. R., Zampino, G., Hamamy, H., Zalloum, Y., Waaler, P. E., Crisponi, G., Crisponi, L., Rutsch, F. &lt;strong&gt;Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.&lt;/strong&gt; Europ. J. Hum. Genet. 19: 525-533, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21326283/&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;21326283&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21326283[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/10.1038/ejhg.2010.253&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="21326283">Herholz et al. (2011)</a> reviewed the clinical features of 19 patients with CRLF1 mutations, including 14 classified as having Crisponi syndrome and 5 as having CISS1. Fourteen of the patients had previously been reported. There was some phenotypic overlap between the 2 groups. In particular, a pair of Norwegian brothers reported by <a href="#8" class="mim-tip-reference" title="Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.&lt;/strong&gt; Am. J. Hum. Genet. 72: 375-383, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12509788/&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;12509788&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/346120&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="12509788">Knappskog et al. (2003)</a> as having CISS1 showed feeding difficulties in infancy, and 1 had facial muscle contractions, chubby cheeks, and episodes of hyperthermia early in life, consistent with Crisponi syndrome. In addition, those with a diagnosis of Crisponi syndrome early in life who survived past age 2 years developed scoliosis, and those older than 6 years developed cold-induced sweating. Most of the initial symptoms resolved in the first 2 years of life. Physical measurements did not reveal a significant difference in facial features compared to controls, suggesting that earlier attributes of a long and large face, long philtrum, and broad nose should not be included as obligatory features. <a href="#7" class="mim-tip-reference" title="Herholz, J., Meloni, A., Marongiu, M., Chiappe, F., Deiana, M., Herrero, C. R., Zampino, G., Hamamy, H., Zalloum, Y., Waaler, P. E., Crisponi, G., Crisponi, L., Rutsch, F. &lt;strong&gt;Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.&lt;/strong&gt; Europ. J. Hum. Genet. 19: 525-533, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21326283/&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;21326283&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21326283[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/10.1038/ejhg.2010.253&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="21326283">Herholz et al. (2011)</a> concluded that both groups of patients show a clinical course of varying severity, often depending on the age at examination. Molecular analysis showed no clear genotype/phenotype correlation, but the severity of the disorder was associated with altered secretion of the mutant CRLF1 protein; weak secretion was associated with a more severe phenotype compared to strong secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21326283+12509788" 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="Tuysuz, B., Kasapcopur, O., Yalcinkaya, C., Hasiloglu, Z. I., Knappskog, P. M., Boman, H. &lt;strong&gt;Multiple small hyperintense lesions in the subcortical white matter on cranial MR images in two Turkish brothers with cold-induced sweating syndrome caused by a novel missense mutation in the CRLF1 gene.&lt;/strong&gt; Brain Dev. 35: 596-601, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23026229/&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;23026229&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.braindev.2012.08.011&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="23026229">Tuysuz et al. (2013)</a> reported 2 Turkish brothers, born of consanguineous parents, with CISS1 confirmed by molecular studies. They were 22 and 13 years of age at the time of the report. The older brother showed normal psychomotor development, but had a history of poor feeding and unexplained fevers in the postnatal period. He had a round face, chubby cheeks, broad nasal bridge, anteverted nostrils, short and smooth tongue, adducted thumbs, camptodactyly, progressive kyphoscoliosis, and cryptorchidism. He also had weakness of the lower jaw and a hypernasal voice. Around age 11 to 12 years, he developed cold-induced sweating of the upper body, as well as decreased pain sensitivity. Brain MRI showed multiple small hyperintensities in the subcortical white matter. His younger brother showed delayed psychomotor development and severe mental retardation. He was an irritable baby and had feeding difficulties. Other features, including cold-induced sweating, were similar to those observed in his brother, including the subcortical brain lesions on MRI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23026229" 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 CISS1 in the family reported by <a href="#11" class="mim-tip-reference" title="Sohar, E., Schoenfeld, Y., Udassin, R., Magazanik, A., Revach, M. &lt;strong&gt;Cold-induced profuse sweating on back and chest: a new genetic entity?&lt;/strong&gt; Lancet 312: 1073-1074, 1978. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/82089/&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;82089&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(78)91805-6&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="82089">Sohar et al. (1978)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=82089" 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>Although no parental consanguinity was known in the Norwegian family studied by <a href="#8" class="mim-tip-reference" title="Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.&lt;/strong&gt; Am. J. Hum. Genet. 72: 375-383, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12509788/&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;12509788&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/346120&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="12509788">Knappskog et al. (2003)</a>, genealogic studies revealed several shared ancestors, the closest of which was 9 generations back. Exploiting the possibility in this family of homozygosity for a mutant gene inherited from a common ancestor, <a href="#8" class="mim-tip-reference" title="Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.&lt;/strong&gt; Am. J. Hum. Genet. 72: 375-383, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12509788/&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;12509788&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/346120&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="12509788">Knappskog et al. (2003)</a> employed a combination of coarse-scale homozygosity mapping, based on the Israeli inbred kindred with a common great-grandfather, and finer-scale localization, based on the Norwegian sibship with distant common ancestors. Thus, on the basis of only 4 patients, they identified the candidate chromosomal segment, candidate gene, and likely causative mutations. A maximum multipoint lod score of 4.22 was obtained for a 1.4-Mb homozygous region on chromosome 19p12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509788" 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>Using high-density single-nucleotide polymorphism arrays, <a href="#4" class="mim-tip-reference" title="Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others. &lt;strong&gt;Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.&lt;/strong&gt; Am. J. Hum. Genet. 80: 971-981, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436252/&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;17436252&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/516843&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="17436252">Crisponi et al. (2007)</a> performed homozygosity mapping in 5 Sardinian and 3 Turkish families with Crisponi syndrome and identified a critical region on 19p13.1-p12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17436252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>By DNA sequencing of 25 genes within the candidate region that they identified for cold-induced sweating syndrome, <a href="#8" class="mim-tip-reference" title="Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.&lt;/strong&gt; Am. J. Hum. Genet. 72: 375-383, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12509788/&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;12509788&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/346120&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="12509788">Knappskog et al. (2003)</a> identified potentially deleterious CRLF1 sequence variants (<a href="/entry/604237#0001">604237.0001</a>-<a href="/entry/604237#0003">604237.0003</a>) in both the Israeli and Norwegian families with the disorder. The variants were not found in unaffected control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V. &lt;strong&gt;Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 80: 966-970, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436251/&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;17436251&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436251[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/513608&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="17436251">Dagoneau et al. (2007)</a> identified homozygous or compound heterozygous mutations in the CRLF1 gene (<a href="/entry/604237#0003">604237.0003</a>-<a href="/entry/604237#0006">604237.0006</a>) in 4 children with Crisponi syndrome from 3 unrelated families. The 4 mutations were located in the immunoglobulin-like and type III fibronectin domains, and 3 of them predicted premature termination of translation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17436251" 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 5 Sardinian and 3 Turkish families with Crisponi syndrome, <a href="#4" class="mim-tip-reference" title="Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others. &lt;strong&gt;Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.&lt;/strong&gt; Am. J. Hum. Genet. 80: 971-981, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436252/&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;17436252&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/516843&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="17436252">Crisponi et al. (2007)</a> detected 4 different CRLF1 mutations in the CRLF1 gene, identified as the most prominent candidate gene in the critical region mapped by them to chromosome 19p13.1-p12. <a href="#4" class="mim-tip-reference" title="Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others. &lt;strong&gt;Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.&lt;/strong&gt; Am. J. Hum. Genet. 80: 971-981, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436252/&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;17436252&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/516843&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="17436252">Crisponi et al. (2007)</a> noted that CRLF1 is involved in the pathogenesis of cold-induced sweating syndrome-1, which belongs to a group of conditions with overlapping phenotypes, including cold-induced sweating syndrome-2 (<a href="/entry/610313">610313</a>) and Stuve-Wiedemann syndrome (<a href="/entry/601559">601559</a>). All of these syndromes are caused by mutations of genes in the ciliary neurotrophic factor receptor pathway (see <a href="/entry/118946">118946</a>). Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggested that neither the type nor the location of the CRLF1 mutations pointed to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. <a href="#4" class="mim-tip-reference" title="Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others. &lt;strong&gt;Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.&lt;/strong&gt; Am. J. Hum. Genet. 80: 971-981, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436252/&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;17436252&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/516843&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="17436252">Crisponi et al. (2007)</a> suggested that the syndromes mentioned comprise a family of 'CNTF receptor-related disorders.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17436252" 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 the 2 patients of <a href="#3" class="mim-tip-reference" title="Crisponi, G. &lt;strong&gt;Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?&lt;/strong&gt; Am. J. Med. Genet. 62: 365-371, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8723066/&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;8723066&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q&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="8723066">Crisponi (1996)</a> to survive infancy, <a href="#4" class="mim-tip-reference" title="Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others. &lt;strong&gt;Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.&lt;/strong&gt; Am. J. Hum. Genet. 80: 971-981, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436252/&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;17436252&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/516843&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="17436252">Crisponi et al. (2007)</a> found compound heterozygosity for the same mutations, a 1-bp insertion (<a href="/entry/604237#0003">604237.0003</a>) and a missense mutation (<a href="/entry/604237#0004">604237.0004</a>). <a href="#5" class="mim-tip-reference" title="Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V. &lt;strong&gt;Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 80: 966-970, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17436251/&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;17436251&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17436251[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/513608&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="17436251">Dagoneau et al. (2007)</a> studied 1 of these families as well, and reported the same mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8723066+17436251+17436252" 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 Turkish patient with Crisponi syndrome, <a href="#10" class="mim-tip-reference" title="Okur, I., Tumer, L., Crisponi, L., Eminoglu, F. T., Chiappe, F., Cinaz, P., Yenicesu, I., Hasanoglu, A. &lt;strong&gt;Crisponi syndrome: a new case with additional features and new mutation in CRLF1. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 146A: 3237-3239, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19012339/&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;19012339&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32531&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="19012339">Okur et al. (2008)</a> identified homozygosity for a mutation in the CRLF1 gene (R277X; <a href="/entry/604237#0009">604237.0009</a>). Both parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19012339" 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="#6" class="mim-tip-reference" title="Hahn, A. F., Waaler, P. E., Kvistad, P. H., Bamforth, J. S., Miles, J. H., McLeod, J. G., Knappskog, P. M., Boman, H. &lt;strong&gt;Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood: four new cases.&lt;/strong&gt; J. Neurol. Sci. 293: 68-75, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20400119/&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;20400119&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jns.2010.02.028&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="20400119">Hahn et al. (2010)</a> reviewed and summarized recent findings in the pathogenesis of abnormal sweating in CISS. Sweating is controlled by the sympathetic nervous system, and mature eccrine sweat glands are normally innervated by cholinergic postsynaptic sympathetic neurons. However, during development, the innervating postganglionic sympathetic neurons express a noradrenergic transmitter phenotype. Thus, these sweat gland-innervating neurons normally undergo a process of neurokine-dependent transdifferentiation in response to a retrogradely acting signal secreted from the sweat glands as they become active and mature after birth. This sweat gland-derived signal has been shown to be a member of the IL-6 cytokine family. Both CLCF1 and CRLF1 have been shown to be expressed in sweat glands, and the CLCF1/CRLF1 complex has been shown to induced cholinergic differentiation of sympathetic neurons in culture (<a href="#12" class="mim-tip-reference" title="Stanke, M., Duong, C. V., Pape, M., Geissen, M., Burbach, G., Deller, T., Gascan, H., Otto, C., Parlato, R., Schutz, G., Rohrer, H. &lt;strong&gt;Target-dependent specification of the neurotransmitter phenotype: cholinergic differentiation of sympathetic neurons is mediated in vivo by gp 130 signaling.&lt;/strong&gt; Development 133: 141-150, 2006. Note: Erratum: Development 133: 383 only, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16319110/&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;16319110&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1242/dev.02189&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="16319110">Stanke et al., 2006</a>). Thus, mutations in either of these genes is predicted to result in loss of severely reduced function of the cytokine complex, causing a defect in cholinergic differentiation in sweat glands during development. The distribution of abnormal sweating in affected individuals reflects a complex pattern of function connections between pre- and post-ganglionic sympathetic neurons along the rostrocaudal axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20400119+16319110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Accorsi2003" class="mim-anchor"></a>
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Accorsi, P., Giordano, L., Faravelli, F.
<strong>Crisponi syndrome: report of a further patient.</strong>
Am. J. Med. Genet. 123A: 183-185, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14598344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14598344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14598344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.20292" target="_blank">Full Text</a>]
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Buers, I., Persico, I., Schoning, L., Nitschke, Y., Di Rocco, M., Loi, A., Sahi, P. K., Utine, G. E., Bayraktar-Tanyeri, B., Zampino, G., Cripsoni, G., Rutsch, F., Crisponi, L.
<strong>Crisponi-cold-induced sweating syndrome: differential diagnosis, pathogenesis and treatment concepts.</strong>
Clin. Genet. 97: 209-221, 2020.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31497877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31497877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31497877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/cge.13639" target="_blank">Full Text</a>]
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<a id="Crisponi1996" class="mim-anchor"></a>
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Crisponi, G.
<strong>Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?</strong>
Am. J. Med. Genet. 62: 365-371, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q" target="_blank">Full Text</a>]
</p>
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<li>
<a id="4" class="mim-anchor"></a>
<a id="Crisponi2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others.
<strong>Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.</strong>
Am. J. Hum. Genet. 80: 971-981, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17436252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17436252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17436252[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=17436252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/516843" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
<a id="Dagoneau2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V.
<strong>Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.</strong>
Am. J. Hum. Genet. 80: 966-970, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17436251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17436251</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17436251[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=17436251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/513608" target="_blank">Full Text</a>]
</p>
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<a id="6" class="mim-anchor"></a>
<a id="Hahn2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hahn, A. F., Waaler, P. E., Kvistad, P. H., Bamforth, J. S., Miles, J. H., McLeod, J. G., Knappskog, P. M., Boman, H.
<strong>Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood: four new cases.</strong>
J. Neurol. Sci. 293: 68-75, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20400119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20400119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20400119" 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.jns.2010.02.028" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="Herholz2011" class="mim-anchor"></a>
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Herholz, J., Meloni, A., Marongiu, M., Chiappe, F., Deiana, M., Herrero, C. R., Zampino, G., Hamamy, H., Zalloum, Y., Waaler, P. E., Crisponi, G., Crisponi, L., Rutsch, F.
<strong>Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.</strong>
Europ. J. Hum. Genet. 19: 525-533, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21326283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21326283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21326283[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=21326283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ejhg.2010.253" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
<a id="Knappskog2003" class="mim-anchor"></a>
<div class="">
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Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H.
<strong>Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.</strong>
Am. J. Hum. Genet. 72: 375-383, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509788</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12509788[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=12509788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/346120" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
<a id="Nannenberg2005" class="mim-anchor"></a>
<div class="">
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Nannenberg, E. A., Bijlmer, R., Van Geel, B. M., Hennekam, R. C. M.
<strong>Neonatal paroxysmal trismus and camptodactyly: the Crisponi syndrome.</strong>
Am. J. Med. Genet. 133A: 90-92, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637710</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.30536" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
<a id="Okur2008" class="mim-anchor"></a>
<div class="">
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Okur, I., Tumer, L., Crisponi, L., Eminoglu, F. T., Chiappe, F., Cinaz, P., Yenicesu, I., Hasanoglu, A.
<strong>Crisponi syndrome: a new case with additional features and new mutation in CRLF1. (Letter)</strong>
Am. J. Med. Genet. 146A: 3237-3239, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19012339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19012339</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19012339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.32531" target="_blank">Full Text</a>]
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<a id="Sohar1978" class="mim-anchor"></a>
<div class="">
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Sohar, E., Schoenfeld, Y., Udassin, R., Magazanik, A., Revach, M.
<strong>Cold-induced profuse sweating on back and chest: a new genetic entity?</strong>
Lancet 312: 1073-1074, 1978. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/82089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">82089</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=82089" 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/s0140-6736(78)91805-6" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
<a id="Stanke2006" class="mim-anchor"></a>
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<p class="mim-text-font">
Stanke, M., Duong, C. V., Pape, M., Geissen, M., Burbach, G., Deller, T., Gascan, H., Otto, C., Parlato, R., Schutz, G., Rohrer, H.
<strong>Target-dependent specification of the neurotransmitter phenotype: cholinergic differentiation of sympathetic neurons is mediated in vivo by gp 130 signaling.</strong>
Development 133: 141-150, 2006. Note: Erratum: Development 133: 383 only, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16319110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16319110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16319110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1242/dev.02189" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
<a id="Thomas2008" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thomas, N., Danda, S., Kumar, M., Jana, A. K., Crisponi, G., Meloni, A., Crisponi, L.
<strong>Crisponi syndrome in an Indian patient: a rare differential diagnosis for neonatal tetanus.</strong>
Am. J. Med. Genet. 146A: 2831-2834, 2008.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18837055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18837055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18837055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.32487" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
<a id="Tuysuz2013" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tuysuz, B., Kasapcopur, O., Yalcinkaya, C., Hasiloglu, Z. I., Knappskog, P. M., Boman, H.
<strong>Multiple small hyperintense lesions in the subcortical white matter on cranial MR images in two Turkish brothers with cold-induced sweating syndrome caused by a novel missense mutation in the CRLF1 gene.</strong>
Brain Dev. 35: 596-601, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23026229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23026229</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23026229" 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.braindev.2012.08.011" target="_blank">Full Text</a>]
</p>
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<a id="15" class="mim-anchor"></a>
<a id="Yamazaki2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yamazaki, M., Kosho, T., Kawachi, S., Mikoshiba, M., Takahashi, J., Sano, R., Oka, K., Yoshida, K., Watanabe, T., Kato, H., Komatsu, M., Kawamura, R., Wakui, K., Knappskog, P. M., Boman, H., Fukushima, Y.
<strong>Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation.</strong>
Am. J. Med. Genet. 152A: 764-769, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20186812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20186812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20186812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.33315" target="_blank">Full Text</a>]
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<a id="contributors" class="mim-anchor"></a>
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Cassandra L. Kniffin - updated : 01/06/2020
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Cassandra L. Kniffin - updated : 1/9/2013<br>Marla J. F. O'Neill - updated : 8/14/2006<br>Victor A. McKusick - updated : 1/29/2003
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Victor A. McKusick : 6/4/1986
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carol : 01/08/2020
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ckniffin : 01/06/2020<br>carol : 05/01/2018<br>carol : 04/18/2017<br>carol : 07/28/2016<br>ckniffin : 07/27/2016<br>carol : 07/08/2013<br>carol : 1/11/2013<br>carol : 1/11/2013<br>ckniffin : 1/9/2013<br>terry : 3/25/2009<br>wwang : 9/6/2007<br>wwang : 8/14/2006<br>wwang : 8/14/2006<br>terry : 8/14/2006<br>carol : 2/12/2003<br>tkritzer : 1/30/2003<br>tkritzer : 1/30/2003<br>terry : 1/29/2003<br>mimadm : 3/12/1994<br>supermim : 3/17/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>marie : 3/25/1988<br>reenie : 6/4/1986
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<h3>
<span class="mim-font">
<strong>#</strong> 272430
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<span class="mim-font">
CRISPONI/COLD-INDUCED SWEATING SYNDROME 1; CISS1
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<em>Alternative titles; symbols</em>
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CRISPONI SYNDROME<br />
SOHAR-CRISPONI SYNDROME<br />
MUSCLE CONTRACTIONS, TETANOFORM, WITH CHARACTERISTIC FACE, CAMPTODACTYLY, HYPERTHERMIA, AND SUDDEN DEATH
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<strong>SNOMEDCT:</strong> 702363009, 725097006; &nbsp;
<strong>ORPHA:</strong> 1545, 157820; &nbsp;
<strong>DO:</strong> 0080329; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
19p13.11
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Cold-induced sweating syndrome 1
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272430
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Autosomal recessive
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3
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CRLF1
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604237
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Crisponi/cold-induced sweating syndrome-1 (CISS1) is caused by homozygous or compound heterozygous mutation in the CRLF1 gene (604237) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Crisponi/cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis (summary by Hahn et al., 2010). </p><p>Buers et al. (2020) provided a detailed review of Crisponi/CISS, including clinical features, diagnosis, and evolution of the disease, differential diagnosis, pathogenesis, and recommended management and treatment. </p><p><strong><em>Genetic Heterogeneity of Crisponi/Cold-Induced Sweating Syndrome</em></strong></p><p>
Crisponi/cold-induced sweating syndrome-2 (CISS2; 610313), which is clinically indistinguishable from CISS1, is caused by mutation in the CLCF1 gene (607672) on chromosome 11q13.</p>
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<strong>Nomenclature</strong>
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<p>Sohar et al. (1978) first described cold-induced sweating syndrome, and Crisponi (1996) first described a disorder in infancy that was characterized by muscular contraction of the facial muscles, poor feeding, and episodic fever, often resulting in early death. Both conditions were found to be due to mutation in the same gene. Moreover, it became apparent that most older patients with CISS have a history of features consistent with Crisponi syndrome early in life, indicating that these 2 disorders represent a single entity with variable severity and/or different manifestations according to age. Herholz et al. (2011) suggested the term 'Sohar-Crisponi syndrome' to refer to the disorder. </p>
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<strong>Clinical Features</strong>
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<p>Sohar et al. (1978) observed 2 Israeli sisters who, since childhood, sweated profusely from the back and chest when exposed to temperatures of 7 to 18 degrees C. They also showed high palate, inability to extend the elbows fully, and slight kyphoscoliosis--features demonstrated by neither the parents nor the sibs. The parents shared a grandfather, i.e., were half first cousins. </p><p>Knappskog et al. (2003) observed 2 Norwegian brothers with a clinical phenotype similar to that in the Israeli sisters. The disorder in the brothers was more severe than that in the Israeli sisters, with earlier age of onset, feeding difficulties, serious kyphoscoliosis, and reduced pain and temperature sensitivity. The older brother would not suckle in the neonatal period, leading to dehydration. He was fed first by a nasogastric tube and subsequently by a special sucking device intended for newborn lambs. These feeding problems, complicated by bronchopulmonary and urinary tract infections, led to hospitalization for his first 3 months of life. His younger brother was admitted at 1 day of age, primarily because of respiratory problems. He too did not suckle spontaneously and had to be fed in the same manner as his older brother. Both had difficulty fully opening their mouths. While playing in the snow, the older brother repeatedly experienced frostbite in his hands. Furthermore, he could hold his palms in a flame or put his hands in boiling water without any sensory pain. Both brothers had severe progressive kyphoscoliosis requiring extensive surgery, following which the boys had an unusually low requirement for pain-relieving medication. Both brothers had short hands with pronounced clinodactyly and tapering of fingers. They could not fully extend their elbows. Their sweating problem was noted at the age of approximately 7 years. The patchwise distribution in affected areas closely resembled those described in the Israeli sisters. These areas did not sweat at warm temperatures, during fever episodes, or during exercise. The mother sometimes had to cool her overheated children by putting their feet in cold water. Subtropical environment did not bother these patients. They could stay in bright sunlight without feeling the heat and had no desire to take their clothes off for cooling. </p><p>Crisponi (1996) described an autosomal recessive syndrome observed in 17 newborns (8 males, 9 females) from 12 different families in southern Sardinia. The disorder was evident at birth and was characterized by marked muscular contraction of the facial muscles in response to tactile stimuli or during crying, with trismus and abundant salivation simulating a tetanic spasm. The contractions slowly disappear as the infant calms. There is also neck muscle hypertonia with a tendency to opisthotonos. All patients presented facial anomalies such as large face, chubby cheeks, broad nose with anteverted nostrils, and long philtrum, and showed bilateral camptodactyly. The clinical course in all patients had been characterized by marked feeding difficulties and appearance of variable fever at about 38 degrees centigrade, with peaks of irregular hyperthermia of over 42 degrees centigrade, with onset ranging from birth to a few weeks. In some patients generalized seizures occurred. Death occurred after a period of a few weeks to some months and coincided with fever about 42 degrees centigrade. Crisponi (1996) stated that no useful pathogenetic features were revealed by laboratory investigations. Only 2 patients were alive at the time of report. One patient (aged 14 years) presented slow regression of the dystonic features, while dysthermia and mild psychomotor delay persisted. </p><p>Accorsi et al. (2003) reported a patient with features consistent with Crisponi syndrome. The patient was born of unrelated parents, but both parents came from a small village in a geographically isolated area in northern Italy with a high rate of inbreeding. The pregnancy was complicated by polyhydramnios, and unspecified fetal hand abnormalities were noted by ultrasound. Dysmorphic features were noted at birth, including hypomimic, rounded face, puffy cheeks, broad nose with anteverted nostrils, small mouth with thin and contracted lips, micrognathia, low-set ears, low anterior and posterior hairlines, and a short neck. The hands showed bilateral camptodactyly with ulnar deviation of the fingers and adducted thumbs. The patient exhibited episodes of marked contraction of both facial and neck muscles associated with flexion of the upper limbs, clenching of the hands, and hyperextension of the lower limbs. During these episodes, there was abundant salivation with inability to swallow. Respiratory muscle contractions caused dyspnea, cyanosis, and short apneic spells. The episodes were elicited by crying and by tactile or painful sensation; they did not occur during rest or sleep. At 2 months of age, the patient developed intermittent hyperthermia with fever peaks and rapid falls unassociated with infection. These hyperthermic episodes were followed by hypernatremic dehydration and acute renal failure. The child died at age 4 months of cardiorespiratory failure following a hyperthermic crisis. Skeletal radiography showed mild anomalies and scoliosis. Karyotype analysis identified a pericentric inversion of the heterochromatic region of chromosome 9 of paternal origin. Accorsi et al. (2003) noted the phenotypic similarities to Freeman-Sheldon syndrome (193700) and Stuve-Wiedemann syndrome (601559). </p><p>Nannenberg et al. (2005) reported a 4-year-old boy of Portuguese descent with Crisponi syndrome. Four days after birth, the infant was noted to have bouts of generalized muscle contractions occurring 6 to 10 times per day. The attacks were triggered by external stimuli and involved contraction of the facial muscles, clenching of the hands, jerky movements of the legs, and respiratory abnormalities. The attacks also occurred during sleep. Facial features included round face, broad nose with anteverted nostrils, small mouth, high-arched palate, micrognathia, and retroversion of the ears. He had bilateral camptodactyly and clubfeet. Polysomnography during a paroxysmal event showed a severe obstructive breathing pattern. The overall breathing pattern outside the attacks showed a mix of disorders of control of breathing, including central apnea, hypopnea, obstructive apnea, and long periods of expiratory apneas while the boy was awake. The hyperexcitability disappeared in the course of the first year of life. As he grew older, he developed scoliosis and showed severely delayed psychomotor development. Hyperthermia was never recorded. Nannenberg et al. (2005) noted the similarities to Stuve-Wiedemann syndrome, but concluded that Crisponi syndrome is a unique entity. </p><p>Following up on one of the surviving patients of Crisponi (1996), Dagoneau et al. (2007) noted that she developed scoliosis, which required surgery at age 12 years, and mild developmental delay with attention deficit disorder, requiring special schooling. At age 13 years, growth parameters were at less than -2 SD. See 604237.0003. Dagoneau et al. (2007) also described 2 cousins from a Gypsy family with Crisponi syndrome. One of the patients presented at birth with camptodactyly, overlapping toes, joint contractures of elbows, contractions of facial muscles with trismus, major feeding difficulties, and dysmorphic features (small nose with anteverted nostrils, small mouth, short neck, and low-set ears). He had repeated episodes of hyperthermia (body temperature greater than 42 degrees centigrade) until age 3 years and then profuse sweating of the back. Kyphoscoliosis appeared at age 1 year. At the time of the report, he was 6 years old; growth parameters were at -2 SD, and he had some speech delay. His first cousin also presented with facial muscle contractions, camptodactyly, elbow contractures, and feeding difficulties, and he developed seizures and temperature instability with access of hyperthermia and kyphoscoliosis. </p><p>Thomas et al. (2008) reported an Indian boy, born of consanguineous parents, with Crisponi syndrome. He presented with respiratory distress soon after birth and was noted to have sparse light hair, upslanting eyes, blepharophimosis, broad nose with anteverted nares, long philtrum, retrognathia, and bilateral camptodactyly. He developed tetanus-like spasms on the second day of life characterized by marked contraction of all the muscles, particularly the facial muscles, with trismus, excess salivation, and opisthotonus. Cyanosis and apnea requiring oxygen were present during some of these episodes. He also had episodes of hyperthermia. At 10 months of age, he was still having feeding problems, remained hypertonic with intermittent spasms, and was developmentally delayed. Genetic analysis identified a homozygous 5-kb deletion surrounding exon 1 of the CRLF1 gene. Thomas et al. (2008) emphasized that the dysmorphic features aided in the correct diagnosis, which would otherwise have been considered to be neonatal tetanus. The authors also noted that since the CRLF1 gene is involved in motor neuron survival and in the function of the autonomic nervous system, Crisponi syndrome is characterized by dysautonomic symptoms including disturbances in temperature regulation and neonatal feeding/swallowing, as well as respiratory trismus, facial spasms, and paradoxical sweating. </p><p>Okur et al. (2008) reported a 9-month-old boy of Turkish descent with typical features of Crisponi syndrome who also had velopharyngeal insufficiency, incomplete cleft palate, and thin corpus callosum. </p><p>Yamazaki et al. (2010) reported a 30-year-old Japanese woman, born of consanguineous parents, with CISS1 confirmed by molecular studies. After birth, she showed poor feeding, flexion contractures of the fingers, scoliosis, and recurrent episodes of fever. Notable facial features included large face with thick and arched eyebrows, short nose with anteverted nostrils, full cheeks, and small mouth. Later in childhood, she developed profuse cold-induced sweating as well as decreased sensitivity to pain. She also had severe dental caries requiring complete tooth extraction. Examination at age 30 showed a marfanoid habitus, dolichocephaly, slender face with poor expression, narrow nose, malar hypoplasia, prognathism, and small mouth. Neurologic examination showed hyporeflexia of the upper extremities, and brain MRI showed multiple high-intensity spots on the subcortical white matter of the frontal lobes. She also had camptodactyly with finger joint malalignment and kyphoscoliosis. The longitudinal data from this patient suggested that CISS and Crisponi syndrome are one clinical entity with variable clinical expression or different phenotypic stages according to age. </p><p>Hahn et al. (2010) reported 2 unrelated patients with CISS1. A 24-year-old woman had features of Crisponi syndrome in infancy, including poor feeding, facial muscle contractions, opisthotonus posturing when handled, tight jaw and inability to open the mouth fully, high-arched palate, micrognathia, elbow contractures, and camptodactyly. She could not tolerate summer heat and showed profuse cold-induced sweating of the upper body. She had normal psychomotor development. Later, she developed progressive scoliosis and severe dental decay. Treatment with clonidine alleviated the hyperhidrosis. A 19-year-old Norwegian man had similar features, but was also noted to have decreased pain perception and chronic exposure keratitis due to an inability to close his eyes fully during sleep. </p><p>Herholz et al. (2011) reviewed the clinical features of 19 patients with CRLF1 mutations, including 14 classified as having Crisponi syndrome and 5 as having CISS1. Fourteen of the patients had previously been reported. There was some phenotypic overlap between the 2 groups. In particular, a pair of Norwegian brothers reported by Knappskog et al. (2003) as having CISS1 showed feeding difficulties in infancy, and 1 had facial muscle contractions, chubby cheeks, and episodes of hyperthermia early in life, consistent with Crisponi syndrome. In addition, those with a diagnosis of Crisponi syndrome early in life who survived past age 2 years developed scoliosis, and those older than 6 years developed cold-induced sweating. Most of the initial symptoms resolved in the first 2 years of life. Physical measurements did not reveal a significant difference in facial features compared to controls, suggesting that earlier attributes of a long and large face, long philtrum, and broad nose should not be included as obligatory features. Herholz et al. (2011) concluded that both groups of patients show a clinical course of varying severity, often depending on the age at examination. Molecular analysis showed no clear genotype/phenotype correlation, but the severity of the disorder was associated with altered secretion of the mutant CRLF1 protein; weak secretion was associated with a more severe phenotype compared to strong secretion. </p><p>Tuysuz et al. (2013) reported 2 Turkish brothers, born of consanguineous parents, with CISS1 confirmed by molecular studies. They were 22 and 13 years of age at the time of the report. The older brother showed normal psychomotor development, but had a history of poor feeding and unexplained fevers in the postnatal period. He had a round face, chubby cheeks, broad nasal bridge, anteverted nostrils, short and smooth tongue, adducted thumbs, camptodactyly, progressive kyphoscoliosis, and cryptorchidism. He also had weakness of the lower jaw and a hypernasal voice. Around age 11 to 12 years, he developed cold-induced sweating of the upper body, as well as decreased pain sensitivity. Brain MRI showed multiple small hyperintensities in the subcortical white matter. His younger brother showed delayed psychomotor development and severe mental retardation. He was an irritable baby and had feeding difficulties. Other features, including cold-induced sweating, were similar to those observed in his brother, including the subcortical brain lesions on MRI. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The transmission pattern of CISS1 in the family reported by Sohar et al. (1978) was consistent with autosomal recessive inheritance. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Although no parental consanguinity was known in the Norwegian family studied by Knappskog et al. (2003), genealogic studies revealed several shared ancestors, the closest of which was 9 generations back. Exploiting the possibility in this family of homozygosity for a mutant gene inherited from a common ancestor, Knappskog et al. (2003) employed a combination of coarse-scale homozygosity mapping, based on the Israeli inbred kindred with a common great-grandfather, and finer-scale localization, based on the Norwegian sibship with distant common ancestors. Thus, on the basis of only 4 patients, they identified the candidate chromosomal segment, candidate gene, and likely causative mutations. A maximum multipoint lod score of 4.22 was obtained for a 1.4-Mb homozygous region on chromosome 19p12. </p><p>Using high-density single-nucleotide polymorphism arrays, Crisponi et al. (2007) performed homozygosity mapping in 5 Sardinian and 3 Turkish families with Crisponi syndrome and identified a critical region on 19p13.1-p12. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By DNA sequencing of 25 genes within the candidate region that they identified for cold-induced sweating syndrome, Knappskog et al. (2003) identified potentially deleterious CRLF1 sequence variants (604237.0001-604237.0003) in both the Israeli and Norwegian families with the disorder. The variants were not found in unaffected control individuals. </p><p>Dagoneau et al. (2007) identified homozygous or compound heterozygous mutations in the CRLF1 gene (604237.0003-604237.0006) in 4 children with Crisponi syndrome from 3 unrelated families. The 4 mutations were located in the immunoglobulin-like and type III fibronectin domains, and 3 of them predicted premature termination of translation. </p><p>In 5 Sardinian and 3 Turkish families with Crisponi syndrome, Crisponi et al. (2007) detected 4 different CRLF1 mutations in the CRLF1 gene, identified as the most prominent candidate gene in the critical region mapped by them to chromosome 19p13.1-p12. Crisponi et al. (2007) noted that CRLF1 is involved in the pathogenesis of cold-induced sweating syndrome-1, which belongs to a group of conditions with overlapping phenotypes, including cold-induced sweating syndrome-2 (610313) and Stuve-Wiedemann syndrome (601559). All of these syndromes are caused by mutations of genes in the ciliary neurotrophic factor receptor pathway (see 118946). Comparison of the mutation spectra of Crisponi syndrome and CISS1 suggested that neither the type nor the location of the CRLF1 mutations pointed to a phenotype/genotype correlation that would account for the most severe phenotype in Crisponi syndrome. Crisponi et al. (2007) suggested that the syndromes mentioned comprise a family of 'CNTF receptor-related disorders.' </p><p>In the 2 patients of Crisponi (1996) to survive infancy, Crisponi et al. (2007) found compound heterozygosity for the same mutations, a 1-bp insertion (604237.0003) and a missense mutation (604237.0004). Dagoneau et al. (2007) studied 1 of these families as well, and reported the same mutations. </p><p>In a Turkish patient with Crisponi syndrome, Okur et al. (2008) identified homozygosity for a mutation in the CRLF1 gene (R277X; 604237.0009). Both parents were heterozygous for the mutation. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Pathogenesis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Hahn et al. (2010) reviewed and summarized recent findings in the pathogenesis of abnormal sweating in CISS. Sweating is controlled by the sympathetic nervous system, and mature eccrine sweat glands are normally innervated by cholinergic postsynaptic sympathetic neurons. However, during development, the innervating postganglionic sympathetic neurons express a noradrenergic transmitter phenotype. Thus, these sweat gland-innervating neurons normally undergo a process of neurokine-dependent transdifferentiation in response to a retrogradely acting signal secreted from the sweat glands as they become active and mature after birth. This sweat gland-derived signal has been shown to be a member of the IL-6 cytokine family. Both CLCF1 and CRLF1 have been shown to be expressed in sweat glands, and the CLCF1/CRLF1 complex has been shown to induced cholinergic differentiation of sympathetic neurons in culture (Stanke et al., 2006). Thus, mutations in either of these genes is predicted to result in loss of severely reduced function of the cytokine complex, causing a defect in cholinergic differentiation in sweat glands during development. The distribution of abnormal sweating in affected individuals reflects a complex pattern of function connections between pre- and post-ganglionic sympathetic neurons along the rostrocaudal axis. </p>
</span>
<div>
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</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Accorsi, P., Giordano, L., Faravelli, F.
<strong>Crisponi syndrome: report of a further patient.</strong>
Am. J. Med. Genet. 123A: 183-185, 2003.
[PubMed: 14598344]
[Full Text: https://doi.org/10.1002/ajmg.a.20292]
</p>
</li>
<li>
<p class="mim-text-font">
Buers, I., Persico, I., Schoning, L., Nitschke, Y., Di Rocco, M., Loi, A., Sahi, P. K., Utine, G. E., Bayraktar-Tanyeri, B., Zampino, G., Cripsoni, G., Rutsch, F., Crisponi, L.
<strong>Crisponi-cold-induced sweating syndrome: differential diagnosis, pathogenesis and treatment concepts.</strong>
Clin. Genet. 97: 209-221, 2020.
[PubMed: 31497877]
[Full Text: https://doi.org/10.1111/cge.13639]
</p>
</li>
<li>
<p class="mim-text-font">
Crisponi, G.
<strong>Autosomal recessive disorder with muscle contractions resembling neonatal tetanus, characteristic face, camptodactyly, hyperthermia, and sudden death: a new syndrome?</strong>
Am. J. Med. Genet. 62: 365-371, 1996.
[PubMed: 8723066]
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4&lt;365::AID-AJMG8&gt;3.0.CO;2-Q]
</p>
</li>
<li>
<p class="mim-text-font">
Crisponi, L., Crisponi, G., Meloni, A., Toliat, M. R., Nurnberg, G., Usala, G., Uda, M., Masala, M., Hohne, W., Becker, C., Marongiu, M., Chiappe, F., and 10 others.
<strong>Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1.</strong>
Am. J. Hum. Genet. 80: 971-981, 2007.
[PubMed: 17436252]
[Full Text: https://doi.org/10.1086/516843]
</p>
</li>
<li>
<p class="mim-text-font">
Dagoneau, N., Bellais, S., Blanchet, P., Sarda, P., Al-Gazali, L. I., Di Rocco, M., Huber, C., Djouadi, F., Le Goff, C., Munnich, A., Cormier-Daire, V.
<strong>Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes.</strong>
Am. J. Hum. Genet. 80: 966-970, 2007.
[PubMed: 17436251]
[Full Text: https://doi.org/10.1086/513608]
</p>
</li>
<li>
<p class="mim-text-font">
Hahn, A. F., Waaler, P. E., Kvistad, P. H., Bamforth, J. S., Miles, J. H., McLeod, J. G., Knappskog, P. M., Boman, H.
<strong>Cold-induced sweating syndrome: CISS1 and CISS2: manifestations from infancy to adulthood: four new cases.</strong>
J. Neurol. Sci. 293: 68-75, 2010.
[PubMed: 20400119]
[Full Text: https://doi.org/10.1016/j.jns.2010.02.028]
</p>
</li>
<li>
<p class="mim-text-font">
Herholz, J., Meloni, A., Marongiu, M., Chiappe, F., Deiana, M., Herrero, C. R., Zampino, G., Hamamy, H., Zalloum, Y., Waaler, P. E., Crisponi, G., Crisponi, L., Rutsch, F.
<strong>Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders.</strong>
Europ. J. Hum. Genet. 19: 525-533, 2011.
[PubMed: 21326283]
[Full Text: https://doi.org/10.1038/ejhg.2010.253]
</p>
</li>
<li>
<p class="mim-text-font">
Knappskog, P. M., Majewski, J., Livneh, A., Nilsen, P. T. E., Bringsli, J. S., Ott, J., Boman, H.
<strong>Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.</strong>
Am. J. Hum. Genet. 72: 375-383, 2003.
[PubMed: 12509788]
[Full Text: https://doi.org/10.1086/346120]
</p>
</li>
<li>
<p class="mim-text-font">
Nannenberg, E. A., Bijlmer, R., Van Geel, B. M., Hennekam, R. C. M.
<strong>Neonatal paroxysmal trismus and camptodactyly: the Crisponi syndrome.</strong>
Am. J. Med. Genet. 133A: 90-92, 2005.
[PubMed: 15637710]
[Full Text: https://doi.org/10.1002/ajmg.a.30536]
</p>
</li>
<li>
<p class="mim-text-font">
Okur, I., Tumer, L., Crisponi, L., Eminoglu, F. T., Chiappe, F., Cinaz, P., Yenicesu, I., Hasanoglu, A.
<strong>Crisponi syndrome: a new case with additional features and new mutation in CRLF1. (Letter)</strong>
Am. J. Med. Genet. 146A: 3237-3239, 2008.
[PubMed: 19012339]
[Full Text: https://doi.org/10.1002/ajmg.a.32531]
</p>
</li>
<li>
<p class="mim-text-font">
Sohar, E., Schoenfeld, Y., Udassin, R., Magazanik, A., Revach, M.
<strong>Cold-induced profuse sweating on back and chest: a new genetic entity?</strong>
Lancet 312: 1073-1074, 1978. Note: Originally Volume II.
[PubMed: 82089]
[Full Text: https://doi.org/10.1016/s0140-6736(78)91805-6]
</p>
</li>
<li>
<p class="mim-text-font">
Stanke, M., Duong, C. V., Pape, M., Geissen, M., Burbach, G., Deller, T., Gascan, H., Otto, C., Parlato, R., Schutz, G., Rohrer, H.
<strong>Target-dependent specification of the neurotransmitter phenotype: cholinergic differentiation of sympathetic neurons is mediated in vivo by gp 130 signaling.</strong>
Development 133: 141-150, 2006. Note: Erratum: Development 133: 383 only, 2006.
[PubMed: 16319110]
[Full Text: https://doi.org/10.1242/dev.02189]
</p>
</li>
<li>
<p class="mim-text-font">
Thomas, N., Danda, S., Kumar, M., Jana, A. K., Crisponi, G., Meloni, A., Crisponi, L.
<strong>Crisponi syndrome in an Indian patient: a rare differential diagnosis for neonatal tetanus.</strong>
Am. J. Med. Genet. 146A: 2831-2834, 2008.
[PubMed: 18837055]
[Full Text: https://doi.org/10.1002/ajmg.a.32487]
</p>
</li>
<li>
<p class="mim-text-font">
Tuysuz, B., Kasapcopur, O., Yalcinkaya, C., Hasiloglu, Z. I., Knappskog, P. M., Boman, H.
<strong>Multiple small hyperintense lesions in the subcortical white matter on cranial MR images in two Turkish brothers with cold-induced sweating syndrome caused by a novel missense mutation in the CRLF1 gene.</strong>
Brain Dev. 35: 596-601, 2013.
[PubMed: 23026229]
[Full Text: https://doi.org/10.1016/j.braindev.2012.08.011]
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</li>
<li>
<p class="mim-text-font">
Yamazaki, M., Kosho, T., Kawachi, S., Mikoshiba, M., Takahashi, J., Sano, R., Oka, K., Yoshida, K., Watanabe, T., Kato, H., Komatsu, M., Kawamura, R., Wakui, K., Knappskog, P. M., Boman, H., Fukushima, Y.
<strong>Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation.</strong>
Am. J. Med. Genet. 152A: 764-769, 2010.
[PubMed: 20186812]
[Full Text: https://doi.org/10.1002/ajmg.a.33315]
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Cassandra L. Kniffin - updated : 01/06/2020<br>Cassandra L. Kniffin - updated : 1/9/2013<br>Marla J. F. O&#x27;Neill - updated : 8/14/2006<br>Victor A. McKusick - updated : 1/29/2003
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