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<title>
Entry
- #301040 - ALPHA-THALASSEMIA/IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME, X-LINKED; ATRX
- OMIM
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<span class="h4">#301040</span>
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<strong>Table of Contents</strong>
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<a href="/clinicalSynopsis/301040"><strong>Clinical Synopsis</strong></a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<div><a href="https://clinicaltrials.gov/search?cond=ALPHA-THALASSEMIA/IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME, X-LINKED" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=900&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/alpha-thalassemia-x-linked-intellectual-disability-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0110030" 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/301040" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0110030" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:301040" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 715342005<br />
<strong>ORPHA:</strong> 847<br />
<strong>DO:</strong> 0110030<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>
301040
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
ALPHA-THALASSEMIA/IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME, X-LINKED; ATRX
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, X-LINKED<br />
ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, NONDELETION TYPE<br />
ATR-X SYNDROME<br />
ATR, NONDELETION TYPE
</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/X/447?start=-3&limit=10&highlight=447">
Xq21.1
</a>
</span>
</td>
<td>
<span class="mim-font">
Alpha-thalassemia/impaired intellectual development syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301040"> 301040 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked dominant">XLD</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">
ATRX
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300032"> 300032 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/301040" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/301040" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/301040" 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">
- X-linked dominant <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847879&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847879</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001423" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001423</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001423" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001423</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">
- Postnatal growth deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859778&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859778</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008897" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008897</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008897" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008897</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> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&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 /> -
Absent frontal sinuses <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855669&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855669</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002688" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002688</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002688" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002688</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Mid-face hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858085&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858085</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000272</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">
- Small ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35045004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35045004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q17.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q17.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/744.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">744.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152423&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152423</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008551" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008551</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008551" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008551</a>]</span><br /> -
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 /> -
Posteriorly rotated ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253251006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253251006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431478&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431478</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000358" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000358</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000358" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000358</a>]</span><br /> -
Sensorineural hearing loss (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a&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 /> -
Epicanthal folds <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74824007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74824007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678230</a>, <a href="https://bioportal.bioontology.org/search?q=C0229249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0229249</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</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">
- Low 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 /> -
Small triangular nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845060&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845060</a>]</span><br /> -
Anteverted nares <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> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nares,Anteverted-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de&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">
- 'Carp-like' mouth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856202&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856202</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010806" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010806</a>]</span><br /> -
Full lips <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248177001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248177001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836543</a>, <a href="https://bioportal.bioontology.org/search?q=C0424485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span><br /> -
Protruding tongue <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249872000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249872000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/285503005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">285503005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241442&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241442</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010808</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=a5aa73dcc42adf91162715d89977ff62" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Tongue,Protruding-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=a5aa73dcc42adf91162715d89977ff62&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> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Widely-spaced upper incisors <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1835762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1835762</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001566" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001566</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Perimembranous ventricular septal defect <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109428005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109428005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0344925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011682" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011682</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011682" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011682</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Umbilical hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396347007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396347007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/553.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">553.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019322</a>, <a href="https://bioportal.bioontology.org/search?q=C0041636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
Gastroesophageal reflux <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235595009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235595009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/722884003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">722884003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698065002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698065002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K21.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/530.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">530.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3813607&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3813607</a>, <a href="https://bioportal.bioontology.org/search?q=C4317146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4317146</a>, <a href="https://bioportal.bioontology.org/search?q=C0017168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Shawl scrotum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858539&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858539</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000049" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000049</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000049" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000049</a>]</span><br /> -
Small penis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/34911001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">34911001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276333003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276333003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q55.62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q55.62</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.64" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.64</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240701&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240701</a>, <a href="https://bioportal.bioontology.org/search?q=C4551492&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551492</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030260</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000054" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000054</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000054" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000054</a>]</span><br /> -
Hypospadias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204888000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204888000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/416010008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">416010008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q54" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q54</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.61</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0848558&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0848558</a>, <a href="https://bioportal.bioontology.org/search?q=C1691215&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1691215</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003244" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003244</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000047</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000047" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000047</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cryptorchidism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204878001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010417</a>, <a href="https://bioportal.bioontology.org/search?q=C5441920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Renal agenesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41962002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41962002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204942005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204938007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204938007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q60.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q60.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/753.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">753.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542519&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542519</a>, <a href="https://bioportal.bioontology.org/search?q=C1619700&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1619700</a>, <a href="https://bioportal.bioontology.org/search?q=C1609433&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1609433</a>, <a href="https://bioportal.bioontology.org/search?q=C0158699&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158699</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000110" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000110</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000104" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000104</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010958" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010958</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000104" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000104</a>]</span><br /> -
Hydronephrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43064006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43064006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N13.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N13.30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/591" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">591</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020295&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020295</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000126</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">
- Kyphoscoliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405771009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405771009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405772002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405772002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405773007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405773007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0600033&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0600033</a>, <a href="https://bioportal.bioontology.org/search?q=C0575158&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575158</a>, <a href="https://bioportal.bioontology.org/search?q=C0345392&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0345392</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002751</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0008453" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008453</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002751" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002751</a>]</span><br /> -
Hemivertebra <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68359008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68359008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.49" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.49</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/756.14" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">756.14</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002937" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002937</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coxa valga <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33754009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33754009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16979000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16979000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299236004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299236004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q65.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q65.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.61</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/736.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.31</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158480</a>, <a href="https://bioportal.bioontology.org/search?q=C0152430&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152430</a>, <a href="https://bioportal.bioontology.org/search?q=C0239137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239137</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</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">
- Tapering 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 /> -
Clinodactyly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17268007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17268007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030084</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030084" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030084</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6c6553591f42fb5585fec835d3e3bab3" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Clinodactyly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6c6553591f42fb5585fec835d3e3bab3&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> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Talipes equinovarus <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 />
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<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Mental retardation <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 /> -
Delayed developmental milestones <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274625009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274625009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0476241&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0476241</a>, <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Expressive speech absent <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845056&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845056</a>]</span><br /> -
Hypotonia early <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1860834&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1860834</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008947" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008947</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008947" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008947</a>]</span><br /> -
Spasticity later <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850370</a>]</span><br /> -
Seizures (in 35%) <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 /> -
Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br />
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<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Mild hypochromic microcytic anemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845062&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845062</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44666001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44666001</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004840" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004840</a>]</span><br /> -
Mild form of hemoglobin H (Hb H) disease <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845063&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845063</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hb H erythrocyte inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845061&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845061</a>]</span><br />
</span>
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</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
X-linked mental retardation-hypotonic facies syndrome (<a href="/entry/309580">309580</a>) is an allelic disorder without alpha-thalassemia<br />
</span>
</div>
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</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the ATRX chromatin remodeler gene (ATRX, <a href="/entry/300032#0001">300032.0001</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<p>A number sign (#) is used with this entry because X-linked alpha-thalassemia/impaired intellectual development syndrome is caused by mutation in the ATRX gene (<a href="/entry/300032">300032</a>) on Xq21.</p><p>The 'deletion' type of alpha-thalassemia/impaired intellectual development syndrome (<a href="/entry/141750">141750</a>) is a contiguous gene syndrome due to a deletion in chromosome 16p that involves the hemoglobin alpha-1 (HBA1; <a href="/entry/141800">141800</a>) and alpha-2 (HBA2; <a href="/entry/141850">141850</a>) genes.</p><p>The X-linked mental retardation-hypotonic facies syndrome (<a href="/entry/309580">309580</a>) is also caused by mutation in the ATRX gene.</p>
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<p><a href="#34" class="mim-tip-reference" title="Weatherall, D. J., Higgs, D. R., Bunch, C., Old, J. M., Hunt, D. M., Pressley, L., Clegg, J. B., Bethlenfalvay, N. C., Sjolin, S., Koler, R. D., Magenis, E., Francis, J. L., Bebbington, D. &lt;strong&gt;Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?&lt;/strong&gt; New Eng. J. Med. 305: 607-612, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6267462/&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;6267462&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198109103051103&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="6267462">Weatherall et al. (1981)</a> reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, <a href="/entry/141800">141800</a>) and mental retardation in 3 unrelated patients of northern European descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6267462" 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="#36" class="mim-tip-reference" title="Wilkie, A. O. M., Zeitlin, H. C., Lindenbaum, R. H., Buckle, V. J., Fischel-Ghodsian, N., Chui, D. H. K., Gardner-Medwin, D., MacGillivray, M. H., Weatherall, D. J., Higgs, D. R. &lt;strong&gt;Clinical features and molecular analysis of the alpha-thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha-globin complex.&lt;/strong&gt; Am. J. Hum. Genet. 46: 1127-1140, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2339705/&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;2339705&lt;/a&gt;]" pmid="2339705">Wilkie et al. (1990)</a> reported 5 unrelated patients, 2 of whom were reported by <a href="#34" class="mim-tip-reference" title="Weatherall, D. J., Higgs, D. R., Bunch, C., Old, J. M., Hunt, D. M., Pressley, L., Clegg, J. B., Bethlenfalvay, N. C., Sjolin, S., Koler, R. D., Magenis, E., Francis, J. L., Bebbington, D. &lt;strong&gt;Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?&lt;/strong&gt; New Eng. J. Med. 305: 607-612, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6267462/&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;6267462&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198109103051103&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="6267462">Weatherall et al. (1981)</a>, with mental retardation and alpha-thalassemia without molecular abnormalities of the alpha-globin gene complex on chromosome 16p. The patients showed a strikingly uniform phenotype comprising severe mental handicap, characteristic dysmorphic facies, genital abnormalities, and an unusual, mild form of hemoglobin H disease. Facial features included microcephaly, hypertelorism, epicanthus, a small triangular upturned nose, and flat face. The degree of red blood cell hypochromia and Hb H levels, which varied from 0.7 to 6.7%, were milder than usually found in alpha-thalassemia. Although several approaches failed to find a defect in the alpha-globin genes, 3 patients tested had markedly reduced total mRNA levels of both HBA1 and HBA2. The authors suggested that the responsible locus encoded a trans-acting factor involved in the normal regulation of alpha-globin expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6267462+2339705" 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="Harvey, M. P., Kearney, A., Smith, A., Trent, R. J. &lt;strong&gt;Occurrence of the alpha-thalassaemia-mental retardation syndrome (non-deletional type) in an Australian male.&lt;/strong&gt; J. Med. Genet. 27: 577-581, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2231651/&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;2231651&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.27.9.577&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="2231651">Harvey et al. (1990)</a> described the syndrome in a 21-year-old male and his brother who had died earlier, suggesting X-linked inheritance. DNA analysis showed no deletions within the alpha-globin gene cluster. Hb H bodies were present at a low level (1.6%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2231651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Porteous, M. E. M., Burn, J. &lt;strong&gt;Unknown syndrome. A possible new X linked retardation syndrome: dysmorphic facies, microcephaly, hypotonia, and small genitalia.&lt;/strong&gt; J. Med. Genet. 27: 339-340, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2352265/&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;2352265&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.27.5.339&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="2352265">Porteous and Burn (1990)</a> described a 6-year-old boy who had a maternal uncle with an X-linked mental retardation syndrome, and suggested that their case resembled 2 brothers previously thought to have an atypical form of the Coffin-Lowry syndrome (<a href="/entry/303600">303600</a>) (illustrated in Smith's Recognizable Patterns of Human Malformation, <a href="#17" class="mim-tip-reference" title="Jones, K. L. &lt;strong&gt;Smith&#x27;s Recognizable Patterns of Human Malformation. (4th ed.)&lt;/strong&gt; Philadelphia: W. B. Saunders (pub.) 1988. P. 237."None>Jones, 1988</a>). However, <a href="#35" class="mim-tip-reference" title="Wilkie, A. O. M., Pembrey, M. E., Gibbons, R. J., Higgs, D. R., Porteous, M. E. M., Burn, J., Winter, R. M. &lt;strong&gt;The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. (Letter)&lt;/strong&gt; J. Med. Genet. 28: 724 only, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1941971/&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;1941971&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.10.724&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="1941971">Wilkie et al. (1991)</a> found that there were hematologic signs of the nondeletion ATR syndrome in the patient reported by <a href="#27" class="mim-tip-reference" title="Porteous, M. E. M., Burn, J. &lt;strong&gt;Unknown syndrome. A possible new X linked retardation syndrome: dysmorphic facies, microcephaly, hypotonia, and small genitalia.&lt;/strong&gt; J. Med. Genet. 27: 339-340, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2352265/&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;2352265&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.27.5.339&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="2352265">Porteous and Burn (1990)</a>. In addition, <a href="#35" class="mim-tip-reference" title="Wilkie, A. O. M., Pembrey, M. E., Gibbons, R. J., Higgs, D. R., Porteous, M. E. M., Burn, J., Winter, R. M. &lt;strong&gt;The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. (Letter)&lt;/strong&gt; J. Med. Genet. 28: 724 only, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1941971/&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;1941971&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.10.724&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="1941971">Wilkie et al. (1991)</a> reported that hematologic evaluation of 1 of the brothers reported in Smith's book showed that he had nondeletion ATR and that a male first-cousin through the maternal line had the same condition. <a href="#35" class="mim-tip-reference" title="Wilkie, A. O. M., Pembrey, M. E., Gibbons, R. J., Higgs, D. R., Porteous, M. E. M., Burn, J., Winter, R. M. &lt;strong&gt;The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. (Letter)&lt;/strong&gt; J. Med. Genet. 28: 724 only, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1941971/&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;1941971&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.10.724&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="1941971">Wilkie et al. (1991)</a> suggested that this condition be called 'X-linked alpha-thalassemia/mental retardation' (ATR-X) to distinguish it from the deletion form. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2352265+1941971" 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 review, <a href="#10" class="mim-tip-reference" title="Gibbons, R. J., Wilkie, A. O. M., Weatherall, D. J., Higgs, D. R. &lt;strong&gt;A newly defined X linked mental retardation syndrome associated with alpha-thalassaemia.&lt;/strong&gt; J. Med. Genet. 28: 729-733, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1770527/&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;1770527&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.11.729&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="1770527">Gibbons et al. (1991)</a> noted that some patients with ATR-X syndrome have normal or only mildly abnormal hematologic indices; thus normal hemoglobin levels and red cell indices do not necessarily exclude the condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1770527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Cole, T. R. P., May, A., Hughes, H. E. &lt;strong&gt;Alpha-thalassaemia/mental retardation syndrome (non-deletional type): report of a family supporting X linked inheritance.&lt;/strong&gt; J. Med. Genet. 28: 734-737, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1770528/&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;1770528&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.11.734&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="1770528">Cole et al. (1991)</a> described an affected boy whose maternal uncle was also affected. The boy had right-sided renal agenesis with left-sided hydronephrosis and hydroureter. He had recurrent hypochromic, microcytic anemia. His otherwise unaffected sister had had recurrent urinary tract infections and persistent renal impairment in the absence of any identifiable renal tract anomaly. <a href="#19" class="mim-tip-reference" title="Kurosawa, K., Akatsuka, A., Ochiai, Y., Ikeda, J., Maekawa, K. &lt;strong&gt;Self-induced vomiting in X-linked alpha-thalassemia/mental retardation syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 63: 505-506, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8967323/&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;8967323&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320630304&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="8967323">Kurosawa et al. (1996)</a> described a boy with self-induced vomiting followed by rumination and noted that <a href="#4" class="mim-tip-reference" title="Cole, T. R. P., May, A., Hughes, H. E. &lt;strong&gt;Alpha-thalassaemia/mental retardation syndrome (non-deletional type): report of a family supporting X linked inheritance.&lt;/strong&gt; J. Med. Genet. 28: 734-737, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1770528/&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;1770528&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.11.734&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="1770528">Cole et al. (1991)</a> made the same observation in a man and his nephew. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1770528+8967323" 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="Donnai, D., Clayton-Smith, J., Gibbons, R. J., Higgs, D. R. &lt;strong&gt;The non-deletion alpha-thalassaemia/mental retardation syndrome: further support for X linkage.&lt;/strong&gt; J. Med. Genet. 28: 742-745, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1770530/&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;1770530&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.11.742&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="1770530">Donnai et al. (1991)</a> described 4 brothers with this syndrome in whom the diagnosis was first suspected because of their characteristic clinical features and was confirmed in each case by the demonstration of Hb H inclusions in a proportion of their red blood cells. Very rare Hb H inclusions were found in the red blood cells of the mother and one sister who both shared some facial features with the affected boys; they were presumed to be carriers of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1770530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Gorlin, R. J. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Minneapolis, Minn. 5/29/1993."None>Gorlin (1993)</a> examined patients with typical features of the ATR-X syndrome, but without hemoglobin H. The facies were identical and mapping studies in several families suggested location of the mutation in the site on the X chromosome involved in ATR-X. The facies of this syndrome, which is often confused with that of Coffin-Lowry syndrome, were marked by telecanthus, epicanthic folds, flat nasal bridge, midface hypoplasia, a carp-shaped mouth with full lips, and small triangular nose with anteverted nostrils. <a href="#12" class="mim-tip-reference" title="Gorlin, R. J. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Minneapolis, Minn. 5/29/1993."None>Gorlin (1993)</a> noted that the alae of the nose extended lower than the columella and septum. All developmental milestones, especially walking, were delayed and speech was almost absent. On further investigation, <a href="#11" class="mim-tip-reference" title="Gibbons, R. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Oxford, England 11/7/1994."None>Gibbons (1994)</a> found that the patients of <a href="#12" class="mim-tip-reference" title="Gorlin, R. J. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Minneapolis, Minn. 5/29/1993."None>Gorlin (1993)</a> did have alpha-thalassemia, as indicated by the presence of hemoglobin H inclusions after use of 1% brilliant cresyl blue staining overnight in buffered solution at room temperature. With the staining, the Hb H inclusions give the erythrocytes the appearance of golf balls.</p><p><a href="#21" class="mim-tip-reference" title="Logie, L. J., Gibbons, R. J., Higgs, D. R., Brown, J. K., Porteous, M. E. M. &lt;strong&gt;Alpha thalassaemia mental retardation (ATR-X): an atypical family.&lt;/strong&gt; Arch. Dis. Child. 70: 439-440, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8017970/&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;8017970&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.70.5.439&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="8017970">Logie et al. (1994)</a> reported a pedigree with 6 affected males in 4 sibships spanning 2 generations. Two affected cousins were described in detail, one of whom had an unusually mild hematologic phenotype. Hb H inclusions, the hallmark of the disorder, were detected in the peripheral red blood cells only after repeated observations. The cousins had strikingly similar facies with telecanthus, anteverted nares, carp-shaped mouth, and large tongue. <a href="#6" class="mim-tip-reference" title="Gibbons, R. J., Brueton, L., Buckle, V. J., Burn, J., Clayton-Smith, J., Davison, B. C. C., Gardner, R. J. M., Homfray, T., Kearney, L., Kingston, H. M., Newbury-Ecob, R., Porteous, M. E. P., Wilkie, A. O. M., Higgs, D. R. &lt;strong&gt;Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).&lt;/strong&gt; Am. J. Med. Genet. 55: 288-299, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726225/&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;7726225&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550309&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="7726225">Gibbons et al. (1995)</a> showed that the hematologic findings in ATR-X may vary widely; indeed, in some cases, the manifestation of alpha-thalassemia may be subtle and missed without repeated examinations. <a href="#25" class="mim-tip-reference" title="McPherson, E. W., Clemens, M. M., Gibbons, R. J., Higgs, D. R. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.&lt;/strong&gt; Am. J. Med. Genet. 55: 302-306, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726227/&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;7726227&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550311&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="7726227">McPherson et al. (1995)</a> described a kindred with 4 affected members. The hematologic abnormality was not detected on routine hematologic studies, including hemoglobin electrophoresis, but the patients were found to have hemoglobin H inclusions on brilliant cresyl blue staining of peripheral smears. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8017970+7726227+7726225" 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="#28" class="mim-tip-reference" title="Reardon, W., Gibbons, R. J., Winter, R. M., Baraitser, M. &lt;strong&gt;Male pseudohermaphroditism in sibs with the alpha-thalassemia/mental retardation (ATR-X) syndrome.&lt;/strong&gt; Am. J. Med. Genet. 55: 285-287, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726224/&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;7726224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550308&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="7726224">Reardon et al. (1995)</a> reported 2 phenotypic females with a 46,XY karyotype who had abnormalities of the external genitalia resulting in male pseudohermaphroditism. They pointed out that 1 of the 5 original patients described in defining the ATR-X syndrome was a phenotypic female with a 46,XY karyotype (<a href="#36" class="mim-tip-reference" title="Wilkie, A. O. M., Zeitlin, H. C., Lindenbaum, R. H., Buckle, V. J., Fischel-Ghodsian, N., Chui, D. H. K., Gardner-Medwin, D., MacGillivray, M. H., Weatherall, D. J., Higgs, D. R. &lt;strong&gt;Clinical features and molecular analysis of the alpha-thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha-globin complex.&lt;/strong&gt; Am. J. Hum. Genet. 46: 1127-1140, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2339705/&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;2339705&lt;/a&gt;]" pmid="2339705">Wilkie et al., 1990</a>). <a href="#25" class="mim-tip-reference" title="McPherson, E. W., Clemens, M. M., Gibbons, R. J., Higgs, D. R. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.&lt;/strong&gt; Am. J. Med. Genet. 55: 302-306, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726227/&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;7726227&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550311&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="7726227">McPherson et al. (1995)</a> described genital anomalies that led to a female sex of rearing in 3 of 4 affected members of a family. <a href="#6" class="mim-tip-reference" title="Gibbons, R. J., Brueton, L., Buckle, V. J., Burn, J., Clayton-Smith, J., Davison, B. C. C., Gardner, R. J. M., Homfray, T., Kearney, L., Kingston, H. M., Newbury-Ecob, R., Porteous, M. E. P., Wilkie, A. O. M., Higgs, D. R. &lt;strong&gt;Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).&lt;/strong&gt; Am. J. Med. Genet. 55: 288-299, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726225/&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;7726225&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550309&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="7726225">Gibbons et al. (1995)</a> emphasized the progressive coarsening of the facial appearance. <a href="#18" class="mim-tip-reference" title="Kuno, T., Ideguchi, H., Yoshida, N., Masuyama, T., Ohta, M., Nishimura, S., Tasaki, H., Miyazaki, S., Hara, H., Matsumoto, K. &lt;strong&gt;A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer.&lt;/strong&gt; Acta Paediat. Jpn. 39: 615-618, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9363663/&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;9363663&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1442-200x.1997.tb03651.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9363663">Kuno et al. (1997)</a> described a 5-year-old Japanese boy with this condition. He had an abnormal hemoglobin which was found to consist exclusively of a beta subunit. Severe mental retardation and hypoplastic penis and testes were present. Anemia was only mild (hematocrit 35.8%). The family history was unremarkable. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7726224+9363663+2339705+7726227+7726225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Martinez, F., Tomas, M., Millan, J. M., Fernandez, A., Palau, F., Prieto, F. &lt;strong&gt;Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.&lt;/strong&gt; J. Med. Genet. 35: 284-287, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9598720/&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;9598720&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.35.4.284&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9598720">Martinez et al. (1998)</a> reported 2 brothers and 1 maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. Some facial dysmorphic features were present. <a href="#23" class="mim-tip-reference" title="Martinez, F., Tomas, M., Millan, J. M., Fernandez, A., Palau, F., Prieto, F. &lt;strong&gt;Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.&lt;/strong&gt; J. Med. Genet. 35: 284-287, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9598720/&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;9598720&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.35.4.284&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9598720">Martinez et al. (1998)</a> pointed out the similarity in phenotype between their family and that described by <a href="#29" class="mim-tip-reference" title="Sutherland, G. R., Gedeon, A. K., Haan, E. A., Woodroffe, P., Mulley, J. C. &lt;strong&gt;Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia.&lt;/strong&gt; Am. J. Med. Genet. 30: 493-508, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3177467/&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;3177467&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320300152&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="3177467">Sutherland et al. (1988)</a> (see <a href="/entry/309500">309500</a>). They suggested that the greater phenotypic severity in their family was due to allelic heterogeneity. X-inactivation analysis of 1 potential and 3 obligate carriers showed nonrandom inactivation of the disease-linked variant. On further analysis of this family, <a href="#22" class="mim-tip-reference" title="Lossi, A. M., Millan, J. M., Villard, L., Orellana, C., Cardoso, C., Prieto, F., Fontes, M., Martinez, F. &lt;strong&gt;Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 558-562, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10417298/&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;10417298&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302499&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="10417298">Lossi et al. (1999)</a> found that 3% of the patients' erythrocytes showed Hb H inclusions, consistent with ATR-X. <a href="#22" class="mim-tip-reference" title="Lossi, A. M., Millan, J. M., Villard, L., Orellana, C., Cardoso, C., Prieto, F., Fontes, M., Martinez, F. &lt;strong&gt;Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. (Letter)&lt;/strong&gt; Am. J. Hum. Genet. 65: 558-562, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10417298/&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;10417298&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302499&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="10417298">Lossi et al. (1999)</a> also reported dysmorphic facial features, including 'carp-like' triangular mouth, hypertelorism, small triangular nose, and broad nasal root. The hypertonia and spasticity were unusual findings in this family. A mutation was found in the ATRX gene in affected individuals (<a href="/entry/300032#0016">300032.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3177467+9598720+10417298" 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="Gibbons, R. J., Higgs, D. R. &lt;strong&gt;Molecular-clinical spectrum of the ATR-X syndrome.&lt;/strong&gt; Am. J. Med. Genet. 97: 204-212, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11449489/&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;11449489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1096-8628(200023)97:3&lt;204::AID-AJMG1038&gt;3.0.CO;2-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11449489">Gibbons and Higgs (2000)</a> provided a review of the clinical spectrum of syndromes caused by mutation in the XH2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11449489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Martucciello, G., Lombardi, L., Savasta, S., Gibbons, R. J. &lt;strong&gt;Gastrointestinal phenotype of ATR-X syndrome.&lt;/strong&gt; Am. J. Med. Genet. 140A: 1172-1176, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16688741/&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;16688741&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31248&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="16688741">Martucciello et al. (2006)</a> described male 3-year-old dizygotic twins with ATRX who exhibited gastrointestinal problems including severe regurgitation of food, vomiting, dysphagia, irritability, respiratory disorders, meteorism, and chronic constipation. Barium studies in both twins showed gastric pseudovolvulus, and 24-hour pH monitoring showed severe gastroesophageal reflux. Enzymo-histochemical studies of full-thickness colonic biopsies revealed a complex dysganglionosis: ultrashort Hirschsprung disease (see <a href="/entry/142623">142623</a>) associated with hypoganglionosis. <a href="#24" class="mim-tip-reference" title="Martucciello, G., Lombardi, L., Savasta, S., Gibbons, R. J. &lt;strong&gt;Gastrointestinal phenotype of ATR-X syndrome.&lt;/strong&gt; Am. J. Med. Genet. 140A: 1172-1176, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16688741/&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;16688741&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31248&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="16688741">Martucciello et al. (2006)</a> reviewed the gastrointestinal phenotype of 128 confirmed cases of ATRX and found that drooling was reported in 36% of cases, gastroesophageal reflux was present in 72%, and constipation in 30%. Fundoplication was performed in 10% of cases, and 9% were fed by gastrostomy. Upper GI bleeding was reported in 10% of cases. Fatal aspiration of vomitus occurred in 3 patients; volvulus was seen in 4 patients, 2 of whom died after intestinal infarction; and 4 patients had recurrent hospitalizations for ileus or pseudoobstruction. <a href="#24" class="mim-tip-reference" title="Martucciello, G., Lombardi, L., Savasta, S., Gibbons, R. J. &lt;strong&gt;Gastrointestinal phenotype of ATR-X syndrome.&lt;/strong&gt; Am. J. Med. Genet. 140A: 1172-1176, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16688741/&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;16688741&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31248&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="16688741">Martucciello et al. (2006)</a> also noted that there were numerous anecdotal reports from parents describing prolonged episodes of patient distress with refusal to eat or drink. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16688741" 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="#16" class="mim-tip-reference" title="Jezela-Stanek, A., Fisher, C., Szarras-Czapnik, M., Olczak-Kowalczyk, D., Gibbons, R. J., Slowikowska-Hilczer, J., Krajewska-Walasek, M. &lt;strong&gt;X-linked alpha thalassaemia/mental retardation syndrome: a case with gonadal dysgenesis, caused by a novel mutation in ATRX gene.&lt;/strong&gt; Clin. Dysmorph. 18: 168-171, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19444090/&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;19444090&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/MCD.0b013e32832a9ea5&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="19444090">Jezela-Stanek et al. (2009)</a> reported a patient with ATRX confirmed by genetic analysis. He had hypertelorism, epicanthal folds, strabismus, short nose with flat bridge and triangular upturned tip, and tented upper lip with everted lower lip. Other features included hypotonia, psychomotor retardation, and hemoglobin H inclusions. The patient also had undescended testes and ambiguous genitalia, which the authors referred to as male pseudohermaphroditism. Laboratory studies showed increased FSH and decreased testosterone. A deceased sib was believed to have been affected and reportedly had ambiguous external genitalia. <a href="#16" class="mim-tip-reference" title="Jezela-Stanek, A., Fisher, C., Szarras-Czapnik, M., Olczak-Kowalczyk, D., Gibbons, R. J., Slowikowska-Hilczer, J., Krajewska-Walasek, M. &lt;strong&gt;X-linked alpha thalassaemia/mental retardation syndrome: a case with gonadal dysgenesis, caused by a novel mutation in ATRX gene.&lt;/strong&gt; Clin. Dysmorph. 18: 168-171, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19444090/&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;19444090&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/MCD.0b013e32832a9ea5&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="19444090">Jezela-Stanek et al. (2009)</a> postulated that the distinctive facial features in ATRX result from facial hypotonia and can be confused with Coffin-Lowry syndrome (CLS; <a href="/entry/303600">303600</a>) or SLO syndromes (SLOS; <a href="/entry/270400">270400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19444090" 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>Based on a literature review, <a href="#20" class="mim-tip-reference" title="Leon, N. Y., Harley, V. R. &lt;strong&gt;ATR-X syndrome: genetics, clinical spectrum, and management.&lt;/strong&gt; Hum. Genet. 140: 1625-1634, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34524523/&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;34524523&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-021-02361-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34524523">Leon and Harley (2021)</a> reported the frequency of clinical features in individuals with ATR-X syndrome. The clinical features were highly variable, even within the same family. The most common feature was intellectual disability, identified in 100% of patients, followed by hematologic abnormalities in 70%, genital abnormalities in 62%, characteristic facies in 55%, skeletal abnormalities in 43%, and microcephaly in 42%. Less frequent features included hypotonia (34%), gastrointestinal problems (30%), seizures (17%), abnormal behavior (10%), heart defects (8%), and osteosarcoma (3%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34524523" 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>Carrier Females</em></strong></p><p>
Studying 7 pedigrees that included individuals with the ATR-X syndrome, <a href="#9" class="mim-tip-reference" title="Gibbons, R. J., Suthers, G. K., Wilkie, A. O. M., Buckle, V. J., Higgs, D. R. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.&lt;/strong&gt; Am. J. Hum. Genet. 51: 1136-1149, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1415255/&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;1415255&lt;/a&gt;]" pmid="1415255">Gibbons et al. (1992)</a> concluded that intellectually normal female carriers could be identified by the presence of rare cells containing Hb H inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation in cells from a variety of tissues. <a href="#25" class="mim-tip-reference" title="McPherson, E. W., Clemens, M. M., Gibbons, R. J., Higgs, D. R. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.&lt;/strong&gt; Am. J. Med. Genet. 55: 302-306, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7726227/&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;7726227&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550311&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="7726227">McPherson et al. (1995)</a> used a combination of skewed X inactivation and haplotype analysis at Xq12-q21.3 to establish carrier status. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1415255+7726227" 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="#32" class="mim-tip-reference" title="Wada, T., Sugie, H., Fukushima, Y., Saitoh, S. &lt;strong&gt;Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.&lt;/strong&gt; Am. J. Med. Genet. 138A: 18-20, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16100724/&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;16100724&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30901&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="16100724">Wada et al. (2005)</a> found skewed X-inactivation patterns (greater than 90:10) in 6 of 7 unaffected Japanese female ATR-X carriers; the 1 carrier with nonskewed X inactivation (72:28) demonstrated moderate mental retardation. The woman did not have dysmorphic features or hemoglobin inclusions. <a href="#32" class="mim-tip-reference" title="Wada, T., Sugie, H., Fukushima, Y., Saitoh, S. &lt;strong&gt;Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.&lt;/strong&gt; Am. J. Med. Genet. 138A: 18-20, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16100724/&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;16100724&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.30901&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="16100724">Wada et al. (2005)</a> concluded that mutations in the ATRX gene may cause mental retardation in females if the chromosome carrying the mutation is not properly inactivated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16100724" 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="Badens, C., Martini, N., Courrier, S., DesPortes, V., Touraine, R., Levy, N., Edery, P. &lt;strong&gt;ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2212-2215, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16955409/&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;16955409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31400&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="16955409">Badens et al. (2006)</a> reported a 4-year-old girl with typical features of the ATR-X syndrome. Molecular studies showed a totally skewed X-inactivation pattern, with the active chromosome carrying a heterozygous mutation in the ATRX gene (<a href="/entry/300032#0018">300032.0018</a>). Neither parent had the mutation in peripheral blood leukocytes, but SNP analysis indicated that the mutation occurred on the maternal chromosome. The child was conceived with assisted reproduction technologies (ART) due to micropolycystic ovaries and endometriosis in the mother. <a href="#2" class="mim-tip-reference" title="Badens, C., Martini, N., Courrier, S., DesPortes, V., Touraine, R., Levy, N., Edery, P. &lt;strong&gt;ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern.&lt;/strong&gt; Am. J. Med. Genet. 140A: 2212-2215, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16955409/&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;16955409&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31400&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="16955409">Badens et al. (2006)</a> suggested that some aspect of ART may have disturbed imprinting in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16955409" 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>By linkage analysis of 7 affected pedigrees, <a href="#9" class="mim-tip-reference" title="Gibbons, R. J., Suthers, G. K., Wilkie, A. O. M., Buckle, V. J., Higgs, D. R. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.&lt;/strong&gt; Am. J. Hum. Genet. 51: 1136-1149, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1415255/&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;1415255&lt;/a&gt;]" pmid="1415255">Gibbons et al. (1992)</a> mapped the ATR-X locus to an 11-cM interval on chromosome Xq12-q21.31 between markers DXS106 and DXYS1X (peak lod score of 5.4 at theta = 0 at DXS72). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415255" 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 3-generation ATR-X family with 3 affected males, <a href="#15" class="mim-tip-reference" title="Houdayer, C., Toutain, A., Ronce, N., Lefort, G., Sarda, P., Taib, J., Briault, S., Lambert, J. C., Moraine, C. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation syndrome: linkage analysis in a new family further supports localization in proximal Xq.&lt;/strong&gt; Ann. Genet. 36: 194-199, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8166423/&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;8166423&lt;/a&gt;]" pmid="8166423">Houdayer et al. (1993)</a> demonstrated a maximum lod score of 2.09 at a recombination fraction of zero for linkage with DXS453 located at the boundary Xq12-q13.1. The nearest flanking loci demonstrating recombination with the disease locus were the androgen receptor (AR; <a href="/entry/313700">313700</a>) at Xq11.2-q12 on the centromeric side and DXS72 at Xq21.1 on the telomeric side. <a href="#15" class="mim-tip-reference" title="Houdayer, C., Toutain, A., Ronce, N., Lefort, G., Sarda, P., Taib, J., Briault, S., Lambert, J. C., Moraine, C. &lt;strong&gt;X-linked alpha-thalassemia/mental retardation syndrome: linkage analysis in a new family further supports localization in proximal Xq.&lt;/strong&gt; Ann. Genet. 36: 194-199, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8166423/&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;8166423&lt;/a&gt;]" pmid="8166423">Houdayer et al. (1993)</a> interpreted their results as compatible with a distal boundary at Xq21.1 instead of Xq21.31 as previously held. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8166423" 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="Gibbons, R. J., Picketts, D. J., Villard, L., Higgs, D. R. &lt;strong&gt;Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).&lt;/strong&gt; Cell 80: 837-845, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7697714/&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;7697714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0092-8674(95)90287-2&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="7697714">Gibbons et al. (1995)</a> performed linkage analysis in 9 families with ATR-X syndrome and identified key recombinants that reduced the area of interest to 1.4 cM (estimated to be 15 Mb) between DXS454 and DXS72 within Xq13.1-q21.1 (<a href="#33" class="mim-tip-reference" title="Wang, L. H., Collins, A., Lawrence, S., Keats, B. J., Morton, N. E. &lt;strong&gt;Integration of gene maps: chromosome X.&lt;/strong&gt; Genomics 22: 590-604, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8001970/&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;8001970&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1994.1432&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="8001970">Wang et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7697714+8001970" 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="#20" class="mim-tip-reference" title="Leon, N. Y., Harley, V. R. &lt;strong&gt;ATR-X syndrome: genetics, clinical spectrum, and management.&lt;/strong&gt; Hum. Genet. 140: 1625-1634, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34524523/&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;34524523&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-021-02361-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34524523">Leon and Harley (2021)</a> recommended that targeted sequencing of the ATRX gene should be the first diagnostic test in patients with more than one hallmark clinical feature of ATR-X syndrome. If a mutation is not identified by this method, other techniques to identify deletions or duplications in the ATRX gene, such as chromosome microarray or MLPA, should be considered. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34524523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In patients with the ATR-X syndrome, <a href="#8" class="mim-tip-reference" title="Gibbons, R. J., Picketts, D. J., Villard, L., Higgs, D. R. &lt;strong&gt;Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).&lt;/strong&gt; Cell 80: 837-845, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7697714/&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;7697714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0092-8674(95)90287-2&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="7697714">Gibbons et al. (1995)</a> identified mutations in the ATRX gene (<a href="/entry/300032#0001">300032.0001</a>-<a href="/entry/300032#0009">300032.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7697714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a family with ATR-X syndrome, <a href="#31" class="mim-tip-reference" title="Villard, L., Toutain, A., Lossi, A.-M., Gecz, J., Houdayer, C., Moraine, C., Fontes, M. &lt;strong&gt;Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia.&lt;/strong&gt; Am. J. Hum. Genet. 58: 499-505, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8644709/&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;8644709&lt;/a&gt;]" pmid="8644709">Villard et al. (1996)</a> identified a splice site mutation in the ATRX gene (<a href="/entry/300032#0010">300032.0010</a>). In 2 first cousins presenting the classic ATR-X phenotype with alpha-thalassemia and Hb H inclusions, only the abnormal transcript was expressed. In a distant cousin presenting with a similar dysmorphic mental retardation phenotype, but without thalassemia, they found that approximately 30% of the ATRX transcripts were normal. These data suggested that the mode of action of the ATRX gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis, and that the mutated splice site could be used with varying efficiency in different individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8644709" 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="Hendrich, B., Bickmore, W. &lt;strong&gt;Human diseases with underlying defects in chromatin structure and modification.&lt;/strong&gt; Hum. Molec. Genet. 10: 2233-2242, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11673406/&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;11673406&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.20.2233&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="11673406">Hendrich and Bickmore (2001)</a> reviewed human disorders that share in common defects of chromatin structure or modification, including the ATR-X spectrum of disorders, ICF syndrome (<a href="/entry/242860">242860</a>), Rett syndrome (<a href="/entry/312750">312750</a>), Rubinstein-Taybi syndrome (<a href="/entry/180849">180849</a>), and Coffin-Lowry syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11673406" 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>Partial Duplication of the ATRX Gene</em></strong></p><p>
<a href="#30" class="mim-tip-reference" title="Thienpont, B., de Ravel, T., Van Esch, H., Van Schoubroeck, D., Moerman, P., Vermeesch, J. R., Fryns, J.-P., Froyen, G., Lacoste, C., Badens, C., Devriendt, K. &lt;strong&gt;Partial duplications of the ATRX gene cause the ATR-X syndrome.&lt;/strong&gt; Europ. J. Hum. Genet. 15: 1094-1097, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17579672/&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;17579672&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5201878&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="17579672">Thienpont et al. (2007)</a> reported 3 patients, including 2 sibs, with the ATRX syndrome due to partial duplications of the ATRX gene. In 1 family, the duplication included exons 2 to 35; in the other family, exons 2 to 29. Further analysis showed that both mothers carried the duplication and both had skewed X inactivation. In 1 patient, ATRX mRNA levels were about 3% of normal values. <a href="#30" class="mim-tip-reference" title="Thienpont, B., de Ravel, T., Van Esch, H., Van Schoubroeck, D., Moerman, P., Vermeesch, J. R., Fryns, J.-P., Froyen, G., Lacoste, C., Badens, C., Devriendt, K. &lt;strong&gt;Partial duplications of the ATRX gene cause the ATR-X syndrome.&lt;/strong&gt; Europ. J. Hum. Genet. 15: 1094-1097, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17579672/&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;17579672&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/sj.ejhg.5201878&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="17579672">Thienpont et al. (2007)</a> noted that the duplications were not identified by sequence analysis and suggested that quantitative analysis to detect copy numbers of the ATRX gene may be required in some cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17579672" 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="Cohn, D. M., Pagon, R. A., Hudgins, L., Schwartz, C. E., Stevenson, R. E., Friez, M. J. &lt;strong&gt;Partial ATRX gene duplication causes ATR-X syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 149A: 2317-2320, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19764021/&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;19764021&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33006&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="19764021">Cohn et al. (2009)</a> reported a family in which 3 males had ATRX syndrome due to a partial intragenic duplication of the ATRX gene that spanned exons 2 to 31. Northern blot analysis failed to identify a full-length transcript, but cDNA sequencing was consistent with some level of expression. The authors noted that complete loss of ATRX is most likely lethal, suggesting that the mutation was likely hypomorphic and associated with some residual protein function. Unaffected obligate carrier females in the family had highly skewed X inactivation. The phenotype was typical for the disorder, although the facial features were not as readily apparent in the 2 older affected individuals. The proband was identified from 2 larger cohorts comprising 300 males with mental retardation. <a href="#3" class="mim-tip-reference" title="Cohn, D. M., Pagon, R. A., Hudgins, L., Schwartz, C. E., Stevenson, R. E., Friez, M. J. &lt;strong&gt;Partial ATRX gene duplication causes ATR-X syndrome. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 149A: 2317-2320, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19764021/&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;19764021&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.33006&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="19764021">Cohn et al. (2009)</a> did not find ATRX duplications in 29 additional males with ATRX syndrome who were negative on sequence analysis, suggesting that duplications are a rare cause of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a review article, <a href="#7" class="mim-tip-reference" title="Gibbons, R. J., Higgs, D. R. &lt;strong&gt;Molecular-clinical spectrum of the ATR-X syndrome.&lt;/strong&gt; Am. J. Med. Genet. 97: 204-212, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11449489/&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;11449489&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1096-8628(200023)97:3&lt;204::AID-AJMG1038&gt;3.0.CO;2-X&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11449489">Gibbons and Higgs (2000)</a> noted that mutations in the ATRX gene resulting in the loss of the C terminal domain are associated with the most severe urogenital abnormalities. However, at other sites, there is no obvious link between genotype and phenotype, and there is considerable variation in the degree of abnormalities seen in individuals with the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11449489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 22 ATRX patients from 16 families, <a href="#1" class="mim-tip-reference" title="Badens, C., Lacoste, C., Philip, N., Martini, N., Courrier, S., Giuliano, F., Verloes, A., Munnich, A., Leheup, B., Burglen, L., Odent, S., Van Esch, H., Levy, N. &lt;strong&gt;Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.&lt;/strong&gt; Clin. Genet. 70: 57-62, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16813605/&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;16813605&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2006.00641.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16813605">Badens et al. (2006)</a> found that those with mutations in the PHD-like domain of the ATRX protein had significantly more severe and permanent psychomotor retardation and significantly more severe urogenital anomalies compared to those with mutations in the helicase domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16813605" 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>Based on a review of the literature, <a href="#20" class="mim-tip-reference" title="Leon, N. Y., Harley, V. R. &lt;strong&gt;ATR-X syndrome: genetics, clinical spectrum, and management.&lt;/strong&gt; Hum. Genet. 140: 1625-1634, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34524523/&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;34524523&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s00439-021-02361-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34524523">Leon and Harley (2021)</a> noted that the ATRX mutations in individuals with ATR-X syndrome who developed osteosarcoma were located in the C-terminal region of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34524523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#26" class="mim-tip-reference" title="Medina, C. F., Mazerolle, C., Wang, Y., Berube, N. G., Coupland, S., Gibbons, R. J., Wallace, V. A., Picketts, D. J. &lt;strong&gt;Altered visual function and interneuron survival in Atrx knockout mice: inference for the human syndrome.&lt;/strong&gt; Hum. Molec. Genet. 18: 966-977, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19088125/&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;19088125&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddn424&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="19088125">Medina et al. (2009)</a> surveyed ATR-X syndrome clinical findings and noted that ocular defects were present in 47 (23%) of 202 patients. They showed that Atrx was expressed in the neuroprogenitor pool in embryonic mouse retina and in all cell types of adult mouse retina except rod photoreceptors. Conditional inactivation of Atrx in mouse retina during embryogenesis resulted in loss of only 2 types of neurons, amacrine and horizontal cells. This defect did not arise from a failure to specify these cells, but rather a defect in interneuron differentiation and survival postnatally. The timing of cell loss was concomitant with light-dependent changes in synaptic organization in mouse retina and with a change in Atrx subnuclear localization within these interneurons. The interneuron defects were associated with functional deficits as demonstrated by reduced b-wave amplitudes upon electroretinogram analysis. <a href="#26" class="mim-tip-reference" title="Medina, C. F., Mazerolle, C., Wang, Y., Berube, N. G., Coupland, S., Gibbons, R. J., Wallace, V. A., Picketts, D. J. &lt;strong&gt;Altered visual function and interneuron survival in Atrx knockout mice: inference for the human syndrome.&lt;/strong&gt; Hum. Molec. Genet. 18: 966-977, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19088125/&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;19088125&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddn424&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="19088125">Medina et al. (2009)</a> proposed a role for Atrx in interneuron survival and differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19088125" 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="Badens2006" class="mim-anchor"></a>
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Badens, C., Lacoste, C., Philip, N., Martini, N., Courrier, S., Giuliano, F., Verloes, A., Munnich, A., Leheup, B., Burglen, L., Odent, S., Van Esch, H., Levy, N.
<strong>Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.</strong>
Clin. Genet. 70: 57-62, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16813605/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16813605</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16813605" 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/j.1399-0004.2006.00641.x" target="_blank">Full Text</a>]
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Badens, C., Martini, N., Courrier, S., DesPortes, V., Touraine, R., Levy, N., Edery, P.
<strong>ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern.</strong>
Am. J. Med. Genet. 140A: 2212-2215, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16955409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16955409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16955409" 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.31400" target="_blank">Full Text</a>]
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Cohn, D. M., Pagon, R. A., Hudgins, L., Schwartz, C. E., Stevenson, R. E., Friez, M. J.
<strong>Partial ATRX gene duplication causes ATR-X syndrome. (Letter)</strong>
Am. J. Med. Genet. 149A: 2317-2320, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19764021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19764021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19764021" 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.33006" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Cole1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, T. R. P., May, A., Hughes, H. E.
<strong>Alpha-thalassaemia/mental retardation syndrome (non-deletional type): report of a family supporting X linked inheritance.</strong>
J. Med. Genet. 28: 734-737, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1770528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1770528</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1770528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.11.734" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Donnai1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Donnai, D., Clayton-Smith, J., Gibbons, R. J., Higgs, D. R.
<strong>The non-deletion alpha-thalassaemia/mental retardation syndrome: further support for X linkage.</strong>
J. Med. Genet. 28: 742-745, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1770530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1770530</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1770530" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.11.742" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Gibbons1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R. J., Brueton, L., Buckle, V. J., Burn, J., Clayton-Smith, J., Davison, B. C. C., Gardner, R. J. M., Homfray, T., Kearney, L., Kingston, H. M., Newbury-Ecob, R., Porteous, M. E. P., Wilkie, A. O. M., Higgs, D. R.
<strong>Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).</strong>
Am. J. Med. Genet. 55: 288-299, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726225" 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.1320550309" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Gibbons2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R. J., Higgs, D. R.
<strong>Molecular-clinical spectrum of the ATR-X syndrome.</strong>
Am. J. Med. Genet. 97: 204-212, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11449489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11449489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11449489" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1096-8628(200023)97:3&lt;204::AID-AJMG1038&gt;3.0.CO;2-X" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Gibbons1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R. J., Picketts, D. J., Villard, L., Higgs, D. R.
<strong>Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).</strong>
Cell 80: 837-845, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7697714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7697714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7697714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0092-8674(95)90287-2" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Gibbons1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R. J., Suthers, G. K., Wilkie, A. O. M., Buckle, V. J., Higgs, D. R.
<strong>X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.</strong>
Am. J. Hum. Genet. 51: 1136-1149, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415255" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Gibbons1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R. J., Wilkie, A. O. M., Weatherall, D. J., Higgs, D. R.
<strong>A newly defined X linked mental retardation syndrome associated with alpha-thalassaemia.</strong>
J. Med. Genet. 28: 729-733, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1770527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1770527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1770527" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.11.729" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Gibbons1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gibbons, R.
<strong>Personal Communication.</strong>
Oxford, England 11/7/1994.
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Gorlin1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gorlin, R. J.
<strong>Personal Communication.</strong>
Minneapolis, Minn. 5/29/1993.
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Harvey1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Harvey, M. P., Kearney, A., Smith, A., Trent, R. J.
<strong>Occurrence of the alpha-thalassaemia-mental retardation syndrome (non-deletional type) in an Australian male.</strong>
J. Med. Genet. 27: 577-581, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2231651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2231651</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2231651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.27.9.577" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Hendrich2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hendrich, B., Bickmore, W.
<strong>Human diseases with underlying defects in chromatin structure and modification.</strong>
Hum. Molec. Genet. 10: 2233-2242, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11673406/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11673406</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11673406" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/10.20.2233" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Houdayer1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Houdayer, C., Toutain, A., Ronce, N., Lefort, G., Sarda, P., Taib, J., Briault, S., Lambert, J. C., Moraine, C.
<strong>X-linked alpha-thalassemia/mental retardation syndrome: linkage analysis in a new family further supports localization in proximal Xq.</strong>
Ann. Genet. 36: 194-199, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8166423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8166423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8166423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Jezela-Stanek2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jezela-Stanek, A., Fisher, C., Szarras-Czapnik, M., Olczak-Kowalczyk, D., Gibbons, R. J., Slowikowska-Hilczer, J., Krajewska-Walasek, M.
<strong>X-linked alpha thalassaemia/mental retardation syndrome: a case with gonadal dysgenesis, caused by a novel mutation in ATRX gene.</strong>
Clin. Dysmorph. 18: 168-171, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19444090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19444090</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19444090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/MCD.0b013e32832a9ea5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Jones1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jones, K. L.
<strong>Smith's Recognizable Patterns of Human Malformation. (4th ed.)</strong>
Philadelphia: W. B. Saunders (pub.) 1988. P. 237.
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Kuno1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kuno, T., Ideguchi, H., Yoshida, N., Masuyama, T., Ohta, M., Nishimura, S., Tasaki, H., Miyazaki, S., Hara, H., Matsumoto, K.
<strong>A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer.</strong>
Acta Paediat. Jpn. 39: 615-618, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9363663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9363663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9363663" 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/j.1442-200x.1997.tb03651.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Kurosawa1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kurosawa, K., Akatsuka, A., Ochiai, Y., Ikeda, J., Maekawa, K.
<strong>Self-induced vomiting in X-linked alpha-thalassemia/mental retardation syndrome. (Letter)</strong>
Am. J. Med. Genet. 63: 505-506, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8967323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8967323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8967323" 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.1320630304" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Leon2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Leon, N. Y., Harley, V. R.
<strong>ATR-X syndrome: genetics, clinical spectrum, and management.</strong>
Hum. Genet. 140: 1625-1634, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34524523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34524523</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34524523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Logie1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Logie, L. J., Gibbons, R. J., Higgs, D. R., Brown, J. K., Porteous, M. E. M.
<strong>Alpha thalassaemia mental retardation (ATR-X): an atypical family.</strong>
Arch. Dis. Child. 70: 439-440, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8017970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8017970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8017970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.70.5.439" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Lossi1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lossi, A. M., Millan, J. M., Villard, L., Orellana, C., Cardoso, C., Prieto, F., Fontes, M., Martinez, F.
<strong>Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. (Letter)</strong>
Am. J. Hum. Genet. 65: 558-562, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10417298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10417298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10417298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302499" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Martinez1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Martinez, F., Tomas, M., Millan, J. M., Fernandez, A., Palau, F., Prieto, F.
<strong>Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.</strong>
J. Med. Genet. 35: 284-287, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9598720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9598720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9598720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Martucciello2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Martucciello, G., Lombardi, L., Savasta, S., Gibbons, R. J.
<strong>Gastrointestinal phenotype of ATR-X syndrome.</strong>
Am. J. Med. Genet. 140A: 1172-1176, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16688741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16688741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16688741" 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.31248" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="McPherson1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McPherson, E. W., Clemens, M. M., Gibbons, R. J., Higgs, D. R.
<strong>X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.</strong>
Am. J. Med. Genet. 55: 302-306, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726227/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726227</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726227" 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.1320550311" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Medina2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Medina, C. F., Mazerolle, C., Wang, Y., Berube, N. G., Coupland, S., Gibbons, R. J., Wallace, V. A., Picketts, D. J.
<strong>Altered visual function and interneuron survival in Atrx knockout mice: inference for the human syndrome.</strong>
Hum. Molec. Genet. 18: 966-977, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19088125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19088125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19088125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddn424" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Porteous1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Porteous, M. E. M., Burn, J.
<strong>Unknown syndrome. A possible new X linked retardation syndrome: dysmorphic facies, microcephaly, hypotonia, and small genitalia.</strong>
J. Med. Genet. 27: 339-340, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2352265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2352265</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2352265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Reardon1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Reardon, W., Gibbons, R. J., Winter, R. M., Baraitser, M.
<strong>Male pseudohermaphroditism in sibs with the alpha-thalassemia/mental retardation (ATR-X) syndrome.</strong>
Am. J. Med. Genet. 55: 285-287, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726224" 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.1320550308" target="_blank">Full Text</a>]
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<a id="Sutherland1988" class="mim-anchor"></a>
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Sutherland, G. R., Gedeon, A. K., Haan, E. A., Woodroffe, P., Mulley, J. C.
<strong>Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia.</strong>
Am. J. Med. Genet. 30: 493-508, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3177467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3177467</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3177467" 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.1320300152" target="_blank">Full Text</a>]
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<a id="Thienpont2007" class="mim-anchor"></a>
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Thienpont, B., de Ravel, T., Van Esch, H., Van Schoubroeck, D., Moerman, P., Vermeesch, J. R., Fryns, J.-P., Froyen, G., Lacoste, C., Badens, C., Devriendt, K.
<strong>Partial duplications of the ATRX gene cause the ATR-X syndrome.</strong>
Europ. J. Hum. Genet. 15: 1094-1097, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17579672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17579672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17579672" 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/sj.ejhg.5201878" target="_blank">Full Text</a>]
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<a id="31" class="mim-anchor"></a>
<a id="Villard1996" class="mim-anchor"></a>
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Villard, L., Toutain, A., Lossi, A.-M., Gecz, J., Houdayer, C., Moraine, C., Fontes, M.
<strong>Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia.</strong>
Am. J. Hum. Genet. 58: 499-505, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8644709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8644709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8644709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Wada2005" class="mim-anchor"></a>
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Wada, T., Sugie, H., Fukushima, Y., Saitoh, S.
<strong>Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.</strong>
Am. J. Med. Genet. 138A: 18-20, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16100724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16100724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16100724" 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.30901" target="_blank">Full Text</a>]
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<a id="33" class="mim-anchor"></a>
<a id="Wang1994" class="mim-anchor"></a>
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Wang, L. H., Collins, A., Lawrence, S., Keats, B. J., Morton, N. E.
<strong>Integration of gene maps: chromosome X.</strong>
Genomics 22: 590-604, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8001970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8001970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8001970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/geno.1994.1432" target="_blank">Full Text</a>]
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<a id="Weatherall1981" class="mim-anchor"></a>
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Weatherall, D. J., Higgs, D. R., Bunch, C., Old, J. M., Hunt, D. M., Pressley, L., Clegg, J. B., Bethlenfalvay, N. C., Sjolin, S., Koler, R. D., Magenis, E., Francis, J. L., Bebbington, D.
<strong>Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?</strong>
New Eng. J. Med. 305: 607-612, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6267462/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6267462</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6267462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198109103051103" target="_blank">Full Text</a>]
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<a id="35" class="mim-anchor"></a>
<a id="Wilkie1991" class="mim-anchor"></a>
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Wilkie, A. O. M., Pembrey, M. E., Gibbons, R. J., Higgs, D. R., Porteous, M. E. M., Burn, J., Winter, R. M.
<strong>The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. (Letter)</strong>
J. Med. Genet. 28: 724 only, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1941971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1941971</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1941971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.28.10.724" target="_blank">Full Text</a>]
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<a id="36" class="mim-anchor"></a>
<a id="Wilkie1990" class="mim-anchor"></a>
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Wilkie, A. O. M., Zeitlin, H. C., Lindenbaum, R. H., Buckle, V. J., Fischel-Ghodsian, N., Chui, D. H. K., Gardner-Medwin, D., MacGillivray, M. H., Weatherall, D. J., Higgs, D. R.
<strong>Clinical features and molecular analysis of the alpha-thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha-globin complex.</strong>
Am. J. Hum. Genet. 46: 1127-1140, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2339705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2339705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2339705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<span class="mim-text-font">
Hilary J. Vernon - updated : 07/19/2022
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Cassandra L. Kniffin - updated : 10/13/2010<br>George E. Tiller - updated : 8/24/2009<br>Cassandra L. Kniffin - updated : 7/31/2009<br>Cassandra L. Kniffin - updated : 12/18/2006<br>Marla J. F. O'Neill - updated : 10/11/2006<br>Cassandra L. Kniffin - updated : 8/24/2006<br>Cassandra L. Kniffin - updated : 9/19/2005<br>Cassandra L. Kniffin - reorganized : 7/14/2005<br>Cassandra L. Kniffin - updated : 6/23/2005<br>Victor A. McKusick - updated : 1/22/2004<br>George E. Tiller - updated : 2/12/2002<br>Victor A. McKusick - updated : 10/3/2000
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Creation Date:
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Victor A. McKusick : 11/7/1991
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 05/22/2023
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carol : 12/18/2022<br>carol : 07/20/2022<br>carol : 07/19/2022<br>carol : 07/09/2016<br>alopez : 7/25/2011<br>wwang : 10/20/2010<br>ckniffin : 10/13/2010<br>terry : 5/12/2010<br>wwang : 8/24/2009<br>wwang : 8/5/2009<br>ckniffin : 7/31/2009<br>wwang : 12/21/2006<br>ckniffin : 12/18/2006<br>wwang : 10/12/2006<br>terry : 10/11/2006<br>wwang : 9/1/2006<br>ckniffin : 8/24/2006<br>wwang : 11/23/2005<br>wwang : 10/3/2005<br>wwang : 9/30/2005<br>ckniffin : 9/19/2005<br>carol : 7/14/2005<br>ckniffin : 6/23/2005<br>ckniffin : 6/15/2005<br>ckniffin : 5/12/2005<br>terry : 1/22/2004<br>cwells : 2/18/2002<br>cwells : 2/12/2002<br>mcapotos : 10/6/2000<br>mcapotos : 10/5/2000<br>terry : 10/3/2000<br>carol : 8/4/1999<br>carol : 8/4/1999<br>mark : 2/12/1998<br>mark : 3/27/1997<br>mark : 6/25/1996<br>mark : 6/25/1996<br>mark : 6/25/1996<br>mark : 6/25/1996<br>mark : 6/25/1996<br>terry : 6/14/1996<br>mark : 3/7/1996<br>terry : 3/4/1996<br>mark : 4/8/1995<br>terry : 1/20/1995<br>carol : 10/6/1994<br>davew : 8/22/1994<br>warfield : 4/19/1994
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<h3>
<span class="mim-font">
<strong>#</strong> 301040
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<span class="mim-font">
ALPHA-THALASSEMIA/IMPAIRED INTELLECTUAL DEVELOPMENT SYNDROME, X-LINKED; ATRX
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<em>Alternative titles; symbols</em>
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ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, X-LINKED<br />
ALPHA-THALASSEMIA/MENTAL RETARDATION SYNDROME, NONDELETION TYPE<br />
ATR-X SYNDROME<br />
ATR, NONDELETION TYPE
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<strong>SNOMEDCT:</strong> 715342005; &nbsp;
<strong>ORPHA:</strong> 847; &nbsp;
<strong>DO:</strong> 0110030; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
Xq21.1
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Alpha-thalassemia/impaired intellectual development syndrome
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301040
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X-linked dominant
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3
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ATRX
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300032
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because X-linked alpha-thalassemia/impaired intellectual development syndrome is caused by mutation in the ATRX gene (300032) on Xq21.</p><p>The 'deletion' type of alpha-thalassemia/impaired intellectual development syndrome (141750) is a contiguous gene syndrome due to a deletion in chromosome 16p that involves the hemoglobin alpha-1 (HBA1; 141800) and alpha-2 (HBA2; 141850) genes.</p><p>The X-linked mental retardation-hypotonic facies syndrome (309580) is also caused by mutation in the ATRX gene.</p>
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<strong>Clinical Features</strong>
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<p>Weatherall et al. (1981) reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, 141800) and mental retardation in 3 unrelated patients of northern European descent. </p><p>Wilkie et al. (1990) reported 5 unrelated patients, 2 of whom were reported by Weatherall et al. (1981), with mental retardation and alpha-thalassemia without molecular abnormalities of the alpha-globin gene complex on chromosome 16p. The patients showed a strikingly uniform phenotype comprising severe mental handicap, characteristic dysmorphic facies, genital abnormalities, and an unusual, mild form of hemoglobin H disease. Facial features included microcephaly, hypertelorism, epicanthus, a small triangular upturned nose, and flat face. The degree of red blood cell hypochromia and Hb H levels, which varied from 0.7 to 6.7%, were milder than usually found in alpha-thalassemia. Although several approaches failed to find a defect in the alpha-globin genes, 3 patients tested had markedly reduced total mRNA levels of both HBA1 and HBA2. The authors suggested that the responsible locus encoded a trans-acting factor involved in the normal regulation of alpha-globin expression. </p><p>Harvey et al. (1990) described the syndrome in a 21-year-old male and his brother who had died earlier, suggesting X-linked inheritance. DNA analysis showed no deletions within the alpha-globin gene cluster. Hb H bodies were present at a low level (1.6%). </p><p>Porteous and Burn (1990) described a 6-year-old boy who had a maternal uncle with an X-linked mental retardation syndrome, and suggested that their case resembled 2 brothers previously thought to have an atypical form of the Coffin-Lowry syndrome (303600) (illustrated in Smith's Recognizable Patterns of Human Malformation, Jones, 1988). However, Wilkie et al. (1991) found that there were hematologic signs of the nondeletion ATR syndrome in the patient reported by Porteous and Burn (1990). In addition, Wilkie et al. (1991) reported that hematologic evaluation of 1 of the brothers reported in Smith's book showed that he had nondeletion ATR and that a male first-cousin through the maternal line had the same condition. Wilkie et al. (1991) suggested that this condition be called 'X-linked alpha-thalassemia/mental retardation' (ATR-X) to distinguish it from the deletion form. </p><p>In a review, Gibbons et al. (1991) noted that some patients with ATR-X syndrome have normal or only mildly abnormal hematologic indices; thus normal hemoglobin levels and red cell indices do not necessarily exclude the condition. </p><p>Cole et al. (1991) described an affected boy whose maternal uncle was also affected. The boy had right-sided renal agenesis with left-sided hydronephrosis and hydroureter. He had recurrent hypochromic, microcytic anemia. His otherwise unaffected sister had had recurrent urinary tract infections and persistent renal impairment in the absence of any identifiable renal tract anomaly. Kurosawa et al. (1996) described a boy with self-induced vomiting followed by rumination and noted that Cole et al. (1991) made the same observation in a man and his nephew. </p><p>Donnai et al. (1991) described 4 brothers with this syndrome in whom the diagnosis was first suspected because of their characteristic clinical features and was confirmed in each case by the demonstration of Hb H inclusions in a proportion of their red blood cells. Very rare Hb H inclusions were found in the red blood cells of the mother and one sister who both shared some facial features with the affected boys; they were presumed to be carriers of the disorder. </p><p>Gorlin (1993) examined patients with typical features of the ATR-X syndrome, but without hemoglobin H. The facies were identical and mapping studies in several families suggested location of the mutation in the site on the X chromosome involved in ATR-X. The facies of this syndrome, which is often confused with that of Coffin-Lowry syndrome, were marked by telecanthus, epicanthic folds, flat nasal bridge, midface hypoplasia, a carp-shaped mouth with full lips, and small triangular nose with anteverted nostrils. Gorlin (1993) noted that the alae of the nose extended lower than the columella and septum. All developmental milestones, especially walking, were delayed and speech was almost absent. On further investigation, Gibbons (1994) found that the patients of Gorlin (1993) did have alpha-thalassemia, as indicated by the presence of hemoglobin H inclusions after use of 1% brilliant cresyl blue staining overnight in buffered solution at room temperature. With the staining, the Hb H inclusions give the erythrocytes the appearance of golf balls.</p><p>Logie et al. (1994) reported a pedigree with 6 affected males in 4 sibships spanning 2 generations. Two affected cousins were described in detail, one of whom had an unusually mild hematologic phenotype. Hb H inclusions, the hallmark of the disorder, were detected in the peripheral red blood cells only after repeated observations. The cousins had strikingly similar facies with telecanthus, anteverted nares, carp-shaped mouth, and large tongue. Gibbons et al. (1995) showed that the hematologic findings in ATR-X may vary widely; indeed, in some cases, the manifestation of alpha-thalassemia may be subtle and missed without repeated examinations. McPherson et al. (1995) described a kindred with 4 affected members. The hematologic abnormality was not detected on routine hematologic studies, including hemoglobin electrophoresis, but the patients were found to have hemoglobin H inclusions on brilliant cresyl blue staining of peripheral smears. </p><p>Reardon et al. (1995) reported 2 phenotypic females with a 46,XY karyotype who had abnormalities of the external genitalia resulting in male pseudohermaphroditism. They pointed out that 1 of the 5 original patients described in defining the ATR-X syndrome was a phenotypic female with a 46,XY karyotype (Wilkie et al., 1990). McPherson et al. (1995) described genital anomalies that led to a female sex of rearing in 3 of 4 affected members of a family. Gibbons et al. (1995) emphasized the progressive coarsening of the facial appearance. Kuno et al. (1997) described a 5-year-old Japanese boy with this condition. He had an abnormal hemoglobin which was found to consist exclusively of a beta subunit. Severe mental retardation and hypoplastic penis and testes were present. Anemia was only mild (hematocrit 35.8%). The family history was unremarkable. </p><p>Martinez et al. (1998) reported 2 brothers and 1 maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia. Some facial dysmorphic features were present. Martinez et al. (1998) pointed out the similarity in phenotype between their family and that described by Sutherland et al. (1988) (see 309500). They suggested that the greater phenotypic severity in their family was due to allelic heterogeneity. X-inactivation analysis of 1 potential and 3 obligate carriers showed nonrandom inactivation of the disease-linked variant. On further analysis of this family, Lossi et al. (1999) found that 3% of the patients' erythrocytes showed Hb H inclusions, consistent with ATR-X. Lossi et al. (1999) also reported dysmorphic facial features, including 'carp-like' triangular mouth, hypertelorism, small triangular nose, and broad nasal root. The hypertonia and spasticity were unusual findings in this family. A mutation was found in the ATRX gene in affected individuals (300032.0016). </p><p>Gibbons and Higgs (2000) provided a review of the clinical spectrum of syndromes caused by mutation in the XH2 gene. </p><p>Martucciello et al. (2006) described male 3-year-old dizygotic twins with ATRX who exhibited gastrointestinal problems including severe regurgitation of food, vomiting, dysphagia, irritability, respiratory disorders, meteorism, and chronic constipation. Barium studies in both twins showed gastric pseudovolvulus, and 24-hour pH monitoring showed severe gastroesophageal reflux. Enzymo-histochemical studies of full-thickness colonic biopsies revealed a complex dysganglionosis: ultrashort Hirschsprung disease (see 142623) associated with hypoganglionosis. Martucciello et al. (2006) reviewed the gastrointestinal phenotype of 128 confirmed cases of ATRX and found that drooling was reported in 36% of cases, gastroesophageal reflux was present in 72%, and constipation in 30%. Fundoplication was performed in 10% of cases, and 9% were fed by gastrostomy. Upper GI bleeding was reported in 10% of cases. Fatal aspiration of vomitus occurred in 3 patients; volvulus was seen in 4 patients, 2 of whom died after intestinal infarction; and 4 patients had recurrent hospitalizations for ileus or pseudoobstruction. Martucciello et al. (2006) also noted that there were numerous anecdotal reports from parents describing prolonged episodes of patient distress with refusal to eat or drink. </p><p>Jezela-Stanek et al. (2009) reported a patient with ATRX confirmed by genetic analysis. He had hypertelorism, epicanthal folds, strabismus, short nose with flat bridge and triangular upturned tip, and tented upper lip with everted lower lip. Other features included hypotonia, psychomotor retardation, and hemoglobin H inclusions. The patient also had undescended testes and ambiguous genitalia, which the authors referred to as male pseudohermaphroditism. Laboratory studies showed increased FSH and decreased testosterone. A deceased sib was believed to have been affected and reportedly had ambiguous external genitalia. Jezela-Stanek et al. (2009) postulated that the distinctive facial features in ATRX result from facial hypotonia and can be confused with Coffin-Lowry syndrome (CLS; 303600) or SLO syndromes (SLOS; 270400). </p><p>Based on a literature review, Leon and Harley (2021) reported the frequency of clinical features in individuals with ATR-X syndrome. The clinical features were highly variable, even within the same family. The most common feature was intellectual disability, identified in 100% of patients, followed by hematologic abnormalities in 70%, genital abnormalities in 62%, characteristic facies in 55%, skeletal abnormalities in 43%, and microcephaly in 42%. Less frequent features included hypotonia (34%), gastrointestinal problems (30%), seizures (17%), abnormal behavior (10%), heart defects (8%), and osteosarcoma (3%). </p><p><strong><em>Carrier Females</em></strong></p><p>
Studying 7 pedigrees that included individuals with the ATR-X syndrome, Gibbons et al. (1992) concluded that intellectually normal female carriers could be identified by the presence of rare cells containing Hb H inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation in cells from a variety of tissues. McPherson et al. (1995) used a combination of skewed X inactivation and haplotype analysis at Xq12-q21.3 to establish carrier status. </p><p>Wada et al. (2005) found skewed X-inactivation patterns (greater than 90:10) in 6 of 7 unaffected Japanese female ATR-X carriers; the 1 carrier with nonskewed X inactivation (72:28) demonstrated moderate mental retardation. The woman did not have dysmorphic features or hemoglobin inclusions. Wada et al. (2005) concluded that mutations in the ATRX gene may cause mental retardation in females if the chromosome carrying the mutation is not properly inactivated. </p><p>Badens et al. (2006) reported a 4-year-old girl with typical features of the ATR-X syndrome. Molecular studies showed a totally skewed X-inactivation pattern, with the active chromosome carrying a heterozygous mutation in the ATRX gene (300032.0018). Neither parent had the mutation in peripheral blood leukocytes, but SNP analysis indicated that the mutation occurred on the maternal chromosome. The child was conceived with assisted reproduction technologies (ART) due to micropolycystic ovaries and endometriosis in the mother. Badens et al. (2006) suggested that some aspect of ART may have disturbed imprinting in this patient. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By linkage analysis of 7 affected pedigrees, Gibbons et al. (1992) mapped the ATR-X locus to an 11-cM interval on chromosome Xq12-q21.31 between markers DXS106 and DXYS1X (peak lod score of 5.4 at theta = 0 at DXS72). </p><p>In a 3-generation ATR-X family with 3 affected males, Houdayer et al. (1993) demonstrated a maximum lod score of 2.09 at a recombination fraction of zero for linkage with DXS453 located at the boundary Xq12-q13.1. The nearest flanking loci demonstrating recombination with the disease locus were the androgen receptor (AR; 313700) at Xq11.2-q12 on the centromeric side and DXS72 at Xq21.1 on the telomeric side. Houdayer et al. (1993) interpreted their results as compatible with a distal boundary at Xq21.1 instead of Xq21.31 as previously held. </p><p>Gibbons et al. (1995) performed linkage analysis in 9 families with ATR-X syndrome and identified key recombinants that reduced the area of interest to 1.4 cM (estimated to be 15 Mb) between DXS454 and DXS72 within Xq13.1-q21.1 (Wang et al., 1994). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Leon and Harley (2021) recommended that targeted sequencing of the ATRX gene should be the first diagnostic test in patients with more than one hallmark clinical feature of ATR-X syndrome. If a mutation is not identified by this method, other techniques to identify deletions or duplications in the ATRX gene, such as chromosome microarray or MLPA, should be considered. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In patients with the ATR-X syndrome, Gibbons et al. (1995) identified mutations in the ATRX gene (300032.0001-300032.0009). </p><p>In affected members of a family with ATR-X syndrome, Villard et al. (1996) identified a splice site mutation in the ATRX gene (300032.0010). In 2 first cousins presenting the classic ATR-X phenotype with alpha-thalassemia and Hb H inclusions, only the abnormal transcript was expressed. In a distant cousin presenting with a similar dysmorphic mental retardation phenotype, but without thalassemia, they found that approximately 30% of the ATRX transcripts were normal. These data suggested that the mode of action of the ATRX gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis, and that the mutated splice site could be used with varying efficiency in different individuals. </p><p>Hendrich and Bickmore (2001) reviewed human disorders that share in common defects of chromatin structure or modification, including the ATR-X spectrum of disorders, ICF syndrome (242860), Rett syndrome (312750), Rubinstein-Taybi syndrome (180849), and Coffin-Lowry syndrome. </p><p><strong><em>Partial Duplication of the ATRX Gene</em></strong></p><p>
Thienpont et al. (2007) reported 3 patients, including 2 sibs, with the ATRX syndrome due to partial duplications of the ATRX gene. In 1 family, the duplication included exons 2 to 35; in the other family, exons 2 to 29. Further analysis showed that both mothers carried the duplication and both had skewed X inactivation. In 1 patient, ATRX mRNA levels were about 3% of normal values. Thienpont et al. (2007) noted that the duplications were not identified by sequence analysis and suggested that quantitative analysis to detect copy numbers of the ATRX gene may be required in some cases. </p><p>Cohn et al. (2009) reported a family in which 3 males had ATRX syndrome due to a partial intragenic duplication of the ATRX gene that spanned exons 2 to 31. Northern blot analysis failed to identify a full-length transcript, but cDNA sequencing was consistent with some level of expression. The authors noted that complete loss of ATRX is most likely lethal, suggesting that the mutation was likely hypomorphic and associated with some residual protein function. Unaffected obligate carrier females in the family had highly skewed X inactivation. The phenotype was typical for the disorder, although the facial features were not as readily apparent in the 2 older affected individuals. The proband was identified from 2 larger cohorts comprising 300 males with mental retardation. Cohn et al. (2009) did not find ATRX duplications in 29 additional males with ATRX syndrome who were negative on sequence analysis, suggesting that duplications are a rare cause of the disorder. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a review article, Gibbons and Higgs (2000) noted that mutations in the ATRX gene resulting in the loss of the C terminal domain are associated with the most severe urogenital abnormalities. However, at other sites, there is no obvious link between genotype and phenotype, and there is considerable variation in the degree of abnormalities seen in individuals with the same mutation. </p><p>Among 22 ATRX patients from 16 families, Badens et al. (2006) found that those with mutations in the PHD-like domain of the ATRX protein had significantly more severe and permanent psychomotor retardation and significantly more severe urogenital anomalies compared to those with mutations in the helicase domain. </p><p>Based on a review of the literature, Leon and Harley (2021) noted that the ATRX mutations in individuals with ATR-X syndrome who developed osteosarcoma were located in the C-terminal region of the gene. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Medina et al. (2009) surveyed ATR-X syndrome clinical findings and noted that ocular defects were present in 47 (23%) of 202 patients. They showed that Atrx was expressed in the neuroprogenitor pool in embryonic mouse retina and in all cell types of adult mouse retina except rod photoreceptors. Conditional inactivation of Atrx in mouse retina during embryogenesis resulted in loss of only 2 types of neurons, amacrine and horizontal cells. This defect did not arise from a failure to specify these cells, but rather a defect in interneuron differentiation and survival postnatally. The timing of cell loss was concomitant with light-dependent changes in synaptic organization in mouse retina and with a change in Atrx subnuclear localization within these interneurons. The interneuron defects were associated with functional deficits as demonstrated by reduced b-wave amplitudes upon electroretinogram analysis. Medina et al. (2009) proposed a role for Atrx in interneuron survival and differentiation. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Badens, C., Lacoste, C., Philip, N., Martini, N., Courrier, S., Giuliano, F., Verloes, A., Munnich, A., Leheup, B., Burglen, L., Odent, S., Van Esch, H., Levy, N.
<strong>Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.</strong>
Clin. Genet. 70: 57-62, 2006.
[PubMed: 16813605]
[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00641.x]
</p>
</li>
<li>
<p class="mim-text-font">
Badens, C., Martini, N., Courrier, S., DesPortes, V., Touraine, R., Levy, N., Edery, P.
<strong>ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern.</strong>
Am. J. Med. Genet. 140A: 2212-2215, 2006.
[PubMed: 16955409]
[Full Text: https://doi.org/10.1002/ajmg.a.31400]
</p>
</li>
<li>
<p class="mim-text-font">
Cohn, D. M., Pagon, R. A., Hudgins, L., Schwartz, C. E., Stevenson, R. E., Friez, M. J.
<strong>Partial ATRX gene duplication causes ATR-X syndrome. (Letter)</strong>
Am. J. Med. Genet. 149A: 2317-2320, 2009.
[PubMed: 19764021]
[Full Text: https://doi.org/10.1002/ajmg.a.33006]
</p>
</li>
<li>
<p class="mim-text-font">
Cole, T. R. P., May, A., Hughes, H. E.
<strong>Alpha-thalassaemia/mental retardation syndrome (non-deletional type): report of a family supporting X linked inheritance.</strong>
J. Med. Genet. 28: 734-737, 1991.
[PubMed: 1770528]
[Full Text: https://doi.org/10.1136/jmg.28.11.734]
</p>
</li>
<li>
<p class="mim-text-font">
Donnai, D., Clayton-Smith, J., Gibbons, R. J., Higgs, D. R.
<strong>The non-deletion alpha-thalassaemia/mental retardation syndrome: further support for X linkage.</strong>
J. Med. Genet. 28: 742-745, 1991.
[PubMed: 1770530]
[Full Text: https://doi.org/10.1136/jmg.28.11.742]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R. J., Brueton, L., Buckle, V. J., Burn, J., Clayton-Smith, J., Davison, B. C. C., Gardner, R. J. M., Homfray, T., Kearney, L., Kingston, H. M., Newbury-Ecob, R., Porteous, M. E. P., Wilkie, A. O. M., Higgs, D. R.
<strong>Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).</strong>
Am. J. Med. Genet. 55: 288-299, 1995.
[PubMed: 7726225]
[Full Text: https://doi.org/10.1002/ajmg.1320550309]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R. J., Higgs, D. R.
<strong>Molecular-clinical spectrum of the ATR-X syndrome.</strong>
Am. J. Med. Genet. 97: 204-212, 2000.
[PubMed: 11449489]
[Full Text: https://doi.org/10.1002/1096-8628(200023)97:3&lt;204::AID-AJMG1038&gt;3.0.CO;2-X]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R. J., Picketts, D. J., Villard, L., Higgs, D. R.
<strong>Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).</strong>
Cell 80: 837-845, 1995.
[PubMed: 7697714]
[Full Text: https://doi.org/10.1016/0092-8674(95)90287-2]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R. J., Suthers, G. K., Wilkie, A. O. M., Buckle, V. J., Higgs, D. R.
<strong>X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.</strong>
Am. J. Hum. Genet. 51: 1136-1149, 1992.
[PubMed: 1415255]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R. J., Wilkie, A. O. M., Weatherall, D. J., Higgs, D. R.
<strong>A newly defined X linked mental retardation syndrome associated with alpha-thalassaemia.</strong>
J. Med. Genet. 28: 729-733, 1991.
[PubMed: 1770527]
[Full Text: https://doi.org/10.1136/jmg.28.11.729]
</p>
</li>
<li>
<p class="mim-text-font">
Gibbons, R.
<strong>Personal Communication.</strong>
Oxford, England 11/7/1994.
</p>
</li>
<li>
<p class="mim-text-font">
Gorlin, R. J.
<strong>Personal Communication.</strong>
Minneapolis, Minn. 5/29/1993.
</p>
</li>
<li>
<p class="mim-text-font">
Harvey, M. P., Kearney, A., Smith, A., Trent, R. J.
<strong>Occurrence of the alpha-thalassaemia-mental retardation syndrome (non-deletional type) in an Australian male.</strong>
J. Med. Genet. 27: 577-581, 1990.
[PubMed: 2231651]
[Full Text: https://doi.org/10.1136/jmg.27.9.577]
</p>
</li>
<li>
<p class="mim-text-font">
Hendrich, B., Bickmore, W.
<strong>Human diseases with underlying defects in chromatin structure and modification.</strong>
Hum. Molec. Genet. 10: 2233-2242, 2001.
[PubMed: 11673406]
[Full Text: https://doi.org/10.1093/hmg/10.20.2233]
</p>
</li>
<li>
<p class="mim-text-font">
Houdayer, C., Toutain, A., Ronce, N., Lefort, G., Sarda, P., Taib, J., Briault, S., Lambert, J. C., Moraine, C.
<strong>X-linked alpha-thalassemia/mental retardation syndrome: linkage analysis in a new family further supports localization in proximal Xq.</strong>
Ann. Genet. 36: 194-199, 1993.
[PubMed: 8166423]
</p>
</li>
<li>
<p class="mim-text-font">
Jezela-Stanek, A., Fisher, C., Szarras-Czapnik, M., Olczak-Kowalczyk, D., Gibbons, R. J., Slowikowska-Hilczer, J., Krajewska-Walasek, M.
<strong>X-linked alpha thalassaemia/mental retardation syndrome: a case with gonadal dysgenesis, caused by a novel mutation in ATRX gene.</strong>
Clin. Dysmorph. 18: 168-171, 2009.
[PubMed: 19444090]
[Full Text: https://doi.org/10.1097/MCD.0b013e32832a9ea5]
</p>
</li>
<li>
<p class="mim-text-font">
Jones, K. L.
<strong>Smith&#x27;s Recognizable Patterns of Human Malformation. (4th ed.)</strong>
Philadelphia: W. B. Saunders (pub.) 1988. P. 237.
</p>
</li>
<li>
<p class="mim-text-font">
Kuno, T., Ideguchi, H., Yoshida, N., Masuyama, T., Ohta, M., Nishimura, S., Tasaki, H., Miyazaki, S., Hara, H., Matsumoto, K.
<strong>A case of X-linked alpha-thalassemia/mental retardation syndrome: analysis of hemoglobin by an automated glycated hemoglobin analyzer.</strong>
Acta Paediat. Jpn. 39: 615-618, 1997.
[PubMed: 9363663]
[Full Text: https://doi.org/10.1111/j.1442-200x.1997.tb03651.x]
</p>
</li>
<li>
<p class="mim-text-font">
Kurosawa, K., Akatsuka, A., Ochiai, Y., Ikeda, J., Maekawa, K.
<strong>Self-induced vomiting in X-linked alpha-thalassemia/mental retardation syndrome. (Letter)</strong>
Am. J. Med. Genet. 63: 505-506, 1996.
[PubMed: 8967323]
[Full Text: https://doi.org/10.1002/ajmg.1320630304]
</p>
</li>
<li>
<p class="mim-text-font">
Leon, N. Y., Harley, V. R.
<strong>ATR-X syndrome: genetics, clinical spectrum, and management.</strong>
Hum. Genet. 140: 1625-1634, 2021.
[PubMed: 34524523]
[Full Text: https://doi.org/10.1007/s00439-021-02361-5]
</p>
</li>
<li>
<p class="mim-text-font">
Logie, L. J., Gibbons, R. J., Higgs, D. R., Brown, J. K., Porteous, M. E. M.
<strong>Alpha thalassaemia mental retardation (ATR-X): an atypical family.</strong>
Arch. Dis. Child. 70: 439-440, 1994.
[PubMed: 8017970]
[Full Text: https://doi.org/10.1136/adc.70.5.439]
</p>
</li>
<li>
<p class="mim-text-font">
Lossi, A. M., Millan, J. M., Villard, L., Orellana, C., Cardoso, C., Prieto, F., Fontes, M., Martinez, F.
<strong>Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias. (Letter)</strong>
Am. J. Hum. Genet. 65: 558-562, 1999.
[PubMed: 10417298]
[Full Text: https://doi.org/10.1086/302499]
</p>
</li>
<li>
<p class="mim-text-font">
Martinez, F., Tomas, M., Millan, J. M., Fernandez, A., Palau, F., Prieto, F.
<strong>Genetic localisation of mental retardation with spastic diplegia to the pericentromeric region of the X chromosome: X inactivation in female carriers.</strong>
J. Med. Genet. 35: 284-287, 1998.
[PubMed: 9598720]
[Full Text: https://doi.org/10.1136/jmg.35.4.284]
</p>
</li>
<li>
<p class="mim-text-font">
Martucciello, G., Lombardi, L., Savasta, S., Gibbons, R. J.
<strong>Gastrointestinal phenotype of ATR-X syndrome.</strong>
Am. J. Med. Genet. 140A: 1172-1176, 2006.
[PubMed: 16688741]
[Full Text: https://doi.org/10.1002/ajmg.a.31248]
</p>
</li>
<li>
<p class="mim-text-font">
McPherson, E. W., Clemens, M. M., Gibbons, R. J., Higgs, D. R.
<strong>X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.</strong>
Am. J. Med. Genet. 55: 302-306, 1995.
[PubMed: 7726227]
[Full Text: https://doi.org/10.1002/ajmg.1320550311]
</p>
</li>
<li>
<p class="mim-text-font">
Medina, C. F., Mazerolle, C., Wang, Y., Berube, N. G., Coupland, S., Gibbons, R. J., Wallace, V. A., Picketts, D. J.
<strong>Altered visual function and interneuron survival in Atrx knockout mice: inference for the human syndrome.</strong>
Hum. Molec. Genet. 18: 966-977, 2009.
[PubMed: 19088125]
[Full Text: https://doi.org/10.1093/hmg/ddn424]
</p>
</li>
<li>
<p class="mim-text-font">
Porteous, M. E. M., Burn, J.
<strong>Unknown syndrome. A possible new X linked retardation syndrome: dysmorphic facies, microcephaly, hypotonia, and small genitalia.</strong>
J. Med. Genet. 27: 339-340, 1990.
[PubMed: 2352265]
[Full Text: https://doi.org/10.1136/jmg.27.5.339]
</p>
</li>
<li>
<p class="mim-text-font">
Reardon, W., Gibbons, R. J., Winter, R. M., Baraitser, M.
<strong>Male pseudohermaphroditism in sibs with the alpha-thalassemia/mental retardation (ATR-X) syndrome.</strong>
Am. J. Med. Genet. 55: 285-287, 1995.
[PubMed: 7726224]
[Full Text: https://doi.org/10.1002/ajmg.1320550308]
</p>
</li>
<li>
<p class="mim-text-font">
Sutherland, G. R., Gedeon, A. K., Haan, E. A., Woodroffe, P., Mulley, J. C.
<strong>Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia.</strong>
Am. J. Med. Genet. 30: 493-508, 1988.
[PubMed: 3177467]
[Full Text: https://doi.org/10.1002/ajmg.1320300152]
</p>
</li>
<li>
<p class="mim-text-font">
Thienpont, B., de Ravel, T., Van Esch, H., Van Schoubroeck, D., Moerman, P., Vermeesch, J. R., Fryns, J.-P., Froyen, G., Lacoste, C., Badens, C., Devriendt, K.
<strong>Partial duplications of the ATRX gene cause the ATR-X syndrome.</strong>
Europ. J. Hum. Genet. 15: 1094-1097, 2007.
[PubMed: 17579672]
[Full Text: https://doi.org/10.1038/sj.ejhg.5201878]
</p>
</li>
<li>
<p class="mim-text-font">
Villard, L., Toutain, A., Lossi, A.-M., Gecz, J., Houdayer, C., Moraine, C., Fontes, M.
<strong>Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia.</strong>
Am. J. Hum. Genet. 58: 499-505, 1996.
[PubMed: 8644709]
</p>
</li>
<li>
<p class="mim-text-font">
Wada, T., Sugie, H., Fukushima, Y., Saitoh, S.
<strong>Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.</strong>
Am. J. Med. Genet. 138A: 18-20, 2005.
[PubMed: 16100724]
[Full Text: https://doi.org/10.1002/ajmg.a.30901]
</p>
</li>
<li>
<p class="mim-text-font">
Wang, L. H., Collins, A., Lawrence, S., Keats, B. J., Morton, N. E.
<strong>Integration of gene maps: chromosome X.</strong>
Genomics 22: 590-604, 1994.
[PubMed: 8001970]
[Full Text: https://doi.org/10.1006/geno.1994.1432]
</p>
</li>
<li>
<p class="mim-text-font">
Weatherall, D. J., Higgs, D. R., Bunch, C., Old, J. M., Hunt, D. M., Pressley, L., Clegg, J. B., Bethlenfalvay, N. C., Sjolin, S., Koler, R. D., Magenis, E., Francis, J. L., Bebbington, D.
<strong>Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?</strong>
New Eng. J. Med. 305: 607-612, 1981.
[PubMed: 6267462]
[Full Text: https://doi.org/10.1056/NEJM198109103051103]
</p>
</li>
<li>
<p class="mim-text-font">
Wilkie, A. O. M., Pembrey, M. E., Gibbons, R. J., Higgs, D. R., Porteous, M. E. M., Burn, J., Winter, R. M.
<strong>The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. (Letter)</strong>
J. Med. Genet. 28: 724 only, 1991.
[PubMed: 1941971]
[Full Text: https://doi.org/10.1136/jmg.28.10.724]
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Wilkie, A. O. M., Zeitlin, H. C., Lindenbaum, R. H., Buckle, V. J., Fischel-Ghodsian, N., Chui, D. H. K., Gardner-Medwin, D., MacGillivray, M. H., Weatherall, D. J., Higgs, D. R.
<strong>Clinical features and molecular analysis of the alpha-thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the alpha-globin complex.</strong>
Am. J. Hum. Genet. 46: 1127-1140, 1990.
[PubMed: 2339705]
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Hilary J. Vernon - updated : 07/19/2022<br>Cassandra L. Kniffin - updated : 10/13/2010<br>George E. Tiller - updated : 8/24/2009<br>Cassandra L. Kniffin - updated : 7/31/2009<br>Cassandra L. Kniffin - updated : 12/18/2006<br>Marla J. F. O&#x27;Neill - updated : 10/11/2006<br>Cassandra L. Kniffin - updated : 8/24/2006<br>Cassandra L. Kniffin - updated : 9/19/2005<br>Cassandra L. Kniffin - reorganized : 7/14/2005<br>Cassandra L. Kniffin - updated : 6/23/2005<br>Victor A. McKusick - updated : 1/22/2004<br>George E. Tiller - updated : 2/12/2002<br>Victor A. McKusick - updated : 10/3/2000
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