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<title>
Entry
- #614979 - RETINAL DYSTROPHY, OPTIC NERVE EDEMA, SPLENOMEGALY, ANHIDROSIS, AND MIGRAINE HEADACHE SYNDROME; ROSAH
- OMIM
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<span class="h4">#614979</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/614979"><strong>Clinical Synopsis</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=RETINAL DYSTROPHY, OPTIC NERVE EDEMA, SPLENOMEGALY, ANHIDROSIS, AND MIGRAINE HEADACHE SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21452&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>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK604494/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<strong>SNOMEDCT:</strong> 771471002<br />
<strong>ORPHA:</strong> 313800<br />
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614979
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<h3>
<span class="mim-font">
RETINAL DYSTROPHY, OPTIC NERVE EDEMA, SPLENOMEGALY, ANHIDROSIS, AND MIGRAINE HEADACHE SYNDROME; ROSAH
</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">
SPLENOMEGALY, CYTOPENIA, AND VISION LOSS
</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/4/494?start=-3&limit=10&highlight=494">
4q25
</a>
</span>
</td>
<td>
<span class="mim-font">
ROSAH syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614979"> 614979 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
ALPK1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607347"> 607347 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/614979" 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/614979" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/614979" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vision loss, of gradual onset, within the first decade of life <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227445&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227445</a>]</span><br /> -
Central vision loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38950008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38950008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152191&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152191</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000603" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000603</a>]</span><br /> -
Color vision loss <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000551" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000551</a>]</span><br /> -
Reduced night vision <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279565</a>]</span><br /> -
Mild lens subluxation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5437028&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5437028</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65814009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65814009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H27.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H27.11</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.32" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.32</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001132" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001132</a>]</span><br /> -
Cataracts <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span><br /> -
Uveitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128473001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128473001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H20.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H20.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042164&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042164</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000554" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000554</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000554" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000554</a>]</span><br /> -
Vitritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95802009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95802009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235812&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235812</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011531" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011531</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011531" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011531</a>]</span><br /> -
Vitreous hemorrhage <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31341008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31341008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H43.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H43.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H43.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H43.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007902</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007902" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007902</a>]</span><br /> -
Retinal hemorrhage, peripapillary or diffuse <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436319&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436319</a>]</span><br /> -
Optic disc pallor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302200001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302200001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0554970&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0554970</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000543</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000543</a>]</span><br /> -
Optic nerve edema, chronic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229567&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229567</a>]</span><br /> -
Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
Macular edema <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37231002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37231002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040049" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040049</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040049" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040049</a>]</span><br /> -
Macular degeneration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422338006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422338006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267718000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267718000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H35.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H35.30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/362.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">362.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242383</a>, <a href="https://bioportal.bioontology.org/search?q=C0024437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000608" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000608</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000608" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000608</a>]</span><br /> -
Loss of foveal reflex <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247144003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247144003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423420&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423420</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030825" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030825</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030825" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030825</a>]</span><br /> -
Retinal dystrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/314407005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">314407005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0854723&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0854723</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000556</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000556" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000556</a>]</span><br /> -
Patchy pigmentation with partial bone-spicule pattern <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436320&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436320</a>]</span><br /> -
Attenuated arterioles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436250&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436250</a>]</span><br /> -
Peripheral retinal atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553016&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553016</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200070</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200070</a>]</span><br /> -
Generalized hyperautofluorescence extending around posterior pole to vascular arcades <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436321&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436321</a>]</span><br /> -
<W2 Reduced or extinguished photopic and scotopic responses seen on full-field electroretinography (ERG) by third decade of life <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436322</a>]</span><br /> -
Severely reduced macular responses seen on pattern ERG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436323&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436323</a>]</span><br /> -
Retinal thickening with indistinct retinal layers seen on optical coherence tomography (OCT) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436324&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436324</a>]</span><br /> -
Peripapillary thickening seen on OCT <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436325&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436325</a>]</span><br /> -
Cystic changes in macula seen on OCT <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436326&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436326</a>]</span><br /> -
Loss of photoreceptor inner and outer segment reflectivity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436327&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436327</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Multiple dental caries (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0743051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0743051</a>]</span><br /> -
Peg-shaped teeth (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29553002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29553002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1162597008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1162597008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266037&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266037</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006342" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006342</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000698" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000698</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000698" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000698</a>]</span><br /> -
Short dental roots <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2678330&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2678330</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006336</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006336</a>]</span><br /> -
Tooth loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37320007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37320007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25540007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25540007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/525.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">525.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0080233&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0080233</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Nasopharynx </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Recurrent upper respiratory infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195708003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195708003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0581381&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0581381</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002788" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002788</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002788" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002788</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> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spleen </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Splenomegaly, massive congestive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229568&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229568</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> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Renal failure, mild (in Australian family) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278162&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278162</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42399005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42399005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N19" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N19</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/586" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">586</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000083" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000083</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Arthritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3723001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3723001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M19.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M19.90</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003864&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003864</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001369</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001369</a>]</span><br /> -
Arthralgia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57676002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57676002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M25.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M25.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/719.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/719.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003862</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Anhidrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14662005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14662005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39659002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39659002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L74.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L74.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/705.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">705.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003028&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003028</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000970" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000970</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000970" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000970</a>]</span><br /> -
Urticaria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64305001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64305001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/126485001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">126485001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247472004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247472004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L50</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/708" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">708</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/708.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">708.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2186740&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2186740</a>, <a href="https://bioportal.bioontology.org/search?q=C0042109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042109</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001025</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001025" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001025</a>]</span><br /> -
Recurrent jaundice (in 1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240074&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240074</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Recurrent headaches (often migrainous in nature) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436318&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436318</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/712826000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">712826000</a>]</span><br /> -
Calcification of the globi pallidi, red nuclei, and substantia nigra <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5883852&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5883852</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Fever, recurrent <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/A68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714772</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386661006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386661006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/50177009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">50177009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.60</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001945" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001945</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Pancytopenia, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229562&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229562</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127034005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/284.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">284.1</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span><br /> -
Neutropenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/303011007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">303011007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165517008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165517008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84828003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84828003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.819</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D70.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.50</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853697</a>, <a href="https://bioportal.bioontology.org/search?q=C0027947&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027947</a>, <a href="https://bioportal.bioontology.org/search?q=C0023530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023530</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>]</span><br />
</span>
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<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Low IgM, mild (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436328&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436328</a>]</span><br /> -
Lymphopenia, mild (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4228403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4228403</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48813009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48813009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.51</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001888" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001888</a>]</span><br />
</span>
</div>
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<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Elevated TNFA levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5437029&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5437029</a>]</span><br /> -
Elevated C-reactive protein <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119971000119104" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119971000119104</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0742906&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0742906</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011227" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011227</a>]</span><br />
</span>
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<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 alpha-kinase 1 gene (ALPK1, <a href="/entry/607347#0001">607347.0001</a>)<br />
</span>
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<p>A number sign (#) is used with this entry because of evidence that retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) is caused by heterozygous mutation in the ALPK1 gene (<a href="/entry/607347">607347</a>) on chromosome 4q25.</p>
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<p>Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) is an autosomal dominant disorder in which affected individuals present in childhood with reduced vision associated with papilledema and low-grade ocular inflammation. Progressive deterioration of visual acuity results in counting fingers to no light perception by the third decade of life. Patients also show anhidrosis, as well as splenomegaly and mild pancytopenia, and most experience headaches that may be migraine-like in nature (<a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al., 2019</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30967659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Clinical Features</strong>
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<p><a href="#2" class="mim-tip-reference" title="Tantravahi, S. K., Williams, L. B., Digre, K. B., Creel, D. J., Smock, K. J., DeAngelis, M. M., Clayton, F. C., Vitale, A. T., Rodgers, G. M. &lt;strong&gt;An inherited disorder with splenomegaly, cytopenias, and vision loss.&lt;/strong&gt; Am. J. Med. Genet. 158A: 475-481, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22307799/&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;22307799&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22307799[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34437&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="22307799">Tantravahi et al. (2012)</a> studied a mother and 2 daughters, who were half-sisters, who had massive splenomegaly, cytopenia, anhidrosis, chronic optic nerve edema, and vision loss. The patients presented in the first decade of life with chronic optic nerve edema followed by slowly progressive vision loss, particularly central, and loss of color vision. In all cases, despite continued optic nerve head edema, lumbar puncture did not show elevated pressure. Although uveitis was seen in 2 patients, it was not present at all exams and testing for common causes of uveitis was negative. Disease progression was similar to a cone or cone-rod dystrophy, with electroretinography (ERG) showing loss of photopic (cone) responses with maintenance of scotopic (rod) responses into the teenage years in 2 patients; however, by ages 15 years to early twenties, all 3 patients had completely extinguished full-field ERGs. In addition, splenomegaly and mild pancytopenia developed in all 3 patients, at ages 9, 12, and 15 years; bone marrow evaluations were normal and splenectomy normalized their complete blood count values, indicating that the cytopenias were due to splenic sequestration. Splenic pathology showed congestion without infiltration or extramedullary hematopoiesis. Both daughters also reported migraine headaches and anhidrosis, and 1 also had episodic urticaria. Immunologic and autoimmune evaluations were negative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22307799" 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="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> restudied the family from Utah (family 1) with splenomegaly, cytopenia, and vision loss that was originally reported by <a href="#2" class="mim-tip-reference" title="Tantravahi, S. K., Williams, L. B., Digre, K. B., Creel, D. J., Smock, K. J., DeAngelis, M. M., Clayton, F. C., Vitale, A. T., Rodgers, G. M. &lt;strong&gt;An inherited disorder with splenomegaly, cytopenias, and vision loss.&lt;/strong&gt; Am. J. Med. Genet. 158A: 475-481, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22307799/&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;22307799&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22307799[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34437&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="22307799">Tantravahi et al. (2012)</a>, and ascertained 5 more similarly affected families, including 1 family from Australia (family 2), 1 from the Netherlands (family 3), 1 from Virginia (family 4), and 1 from Delaware (family 5). In the 16 affected individuals, the most frequent earliest feature was decreased vision associated with optic nerve edema, evident as early as 4 years of age and present by age 12 years in all cases. Low-grade ocular inflammation, unresponsive to steroids or other forms of immunosuppression, was common in affected individuals. In later childhood or in the second decade of life, patients had increasing visual impairment, with abnormal cone function and later loss of rod function in most. By the third decade of life, visual dysfunction was severe with visual acuity ranging from counting fingers to no light perception. In addition to the ocular findings, patients generally had splenomegaly, beginning in the first or second decade of life; 1 patient underwent splenectomy. Hematologic assessment showed chronic mild pancytopenia, which was sometimes exacerbated during periods of viral or other infection. Peripheral smears frequently showed leukopenia with reactive lymphocytosis; bone marrow was normocellular with trilineage hematopoiesis and relative erythroid hyperplasia. Affected individuals also experienced anhidrosis, and migrainous headache was a frequent feature, often associated with episodic fever and back pain. Mild renal impairment was present in some members of family 2, but was not a consistent feature in all patients. <a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> designated the disorder 'ROSAH syndrome' based on the retinopathy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache observed in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30967659+22307799" 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="Zhong, L., Wang, J., Wang, W., Wang, L., Quan, M., Tang, X., Gou, L., Wei, M., Xiao, J., Zhang, T., Sui, R., Zhou, Q., Song, H. &lt;strong&gt;Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1.&lt;/strong&gt; J. Clin. Immun. 40: 350-358, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31939038/&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;31939038&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10875-020-00741-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31939038">Zhong et al. (2020)</a> described 2 unrelated Chinese girls with ROSAH syndrome. In addition to retinal dystrophy, papilledema, splenomegaly, and pancytopenia, both experienced intermittent febrile episodes and were anhidrotic. One patient had undergone elective splenectomy due to concerns about spontaneous rupture, and splenectomy was planned in the other patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31939038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others. &lt;strong&gt;Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.&lt;/strong&gt; Ann. Rheum. Dis. 81: 1453-1464, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35868845/&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;35868845&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/annrheumdis-2022-222629&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="35868845">Kozycki et al. (2022)</a> reported clinical features in 27 patients with ROSAH syndrome. Almost all patients had inflammatory features, including fever, malaise, episodic abdominal pain, headache, cytopenia, and/or retinal vasculitis. Ophthalmologic findings in the cohort included optic nerve elevation, uveitis, retinal vasculitis, and retinal degeneration. Twenty patients had arthralgias, which started in childhood in some patients. Fourteen patients had gastrointestinal symptoms, including pain, gastroesophageal reflux, dysphagia, and/or reflux. Thirteen patients had recurrent headaches, and 7 patients had brain abnormalities seen on brain MRI, including calcification of the globi pallidi, red nucleus, and substantia nigra. Dental abnormalities included multiple caries in 23 patients and enamel defects in 7 patients; 5 patients were edentulous. Almost all patients had hyperhidrosis or anhidrosis, and 4 parous women had dysfunctional breast milk production. Laboratory findings included variably elevated C-reactive protein (CRP; <a href="/entry/123260">123260</a>), transient neutropenia, and cytopenias. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35868845" 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="#1" class="mim-tip-reference" title="Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others. &lt;strong&gt;Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.&lt;/strong&gt; Ann. Rheum. Dis. 81: 1453-1464, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35868845/&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;35868845&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/annrheumdis-2022-222629&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="35868845">Kozycki et al. (2022)</a> reported that 7 of 10 patients with ROSAH syndrome treated with anticytokine therapy had subjective improvement in 1 or more clinical symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35868845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of ROSAH in the family reported by <a href="#2" class="mim-tip-reference" title="Tantravahi, S. K., Williams, L. B., Digre, K. B., Creel, D. J., Smock, K. J., DeAngelis, M. M., Clayton, F. C., Vitale, A. T., Rodgers, G. M. &lt;strong&gt;An inherited disorder with splenomegaly, cytopenias, and vision loss.&lt;/strong&gt; Am. J. Med. Genet. 158A: 475-481, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22307799/&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;22307799&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=22307799[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34437&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="22307799">Tantravahi et al. (2012)</a> was consistent with autosomal dominant inheritance. Genetic analysis by <a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> confirmed autosomal dominant inheritance in this family; <a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> also showed that the mutation occurred de novo in the mother. The heterozygous mutations in other patients reported by <a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> and <a href="#4" class="mim-tip-reference" title="Zhong, L., Wang, J., Wang, W., Wang, L., Quan, M., Tang, X., Gou, L., Wei, M., Xiao, J., Zhang, T., Sui, R., Zhou, Q., Song, H. &lt;strong&gt;Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1.&lt;/strong&gt; J. Clin. Immun. 40: 350-358, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31939038/&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;31939038&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10875-020-00741-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31939038">Zhong et al. (2020)</a> occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30967659+22307799+31939038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Molecular Genetics</strong>
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<p>In all 16 patients from 5 unrelated families with ROSAH syndrome, <a href="#3" class="mim-tip-reference" title="Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others. &lt;strong&gt;ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.&lt;/strong&gt; Genet. Med. 21: 2103-2115, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30967659/&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;30967659&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/s41436-019-0476-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30967659">Williams et al. (2019)</a> identified heterozygosity for the same missense mutation in the ALPK1 gene (T237M; <a href="/entry/607347#0001">607347.0001</a>). The mutation segregated with disease in all families and was not found in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30967659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated Chinese girls with ROSAH syndrome, <a href="#4" class="mim-tip-reference" title="Zhong, L., Wang, J., Wang, W., Wang, L., Quan, M., Tang, X., Gou, L., Wei, M., Xiao, J., Zhang, T., Sui, R., Zhou, Q., Song, H. &lt;strong&gt;Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1.&lt;/strong&gt; J. Clin. Immun. 40: 350-358, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31939038/&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;31939038&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10875-020-00741-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31939038">Zhong et al. (2020)</a> identified heterozygosity for the previously reported recurrent T237M mutation in the ALPK1 gene. The mutation arose de novo in both probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31939038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others. &lt;strong&gt;Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.&lt;/strong&gt; Ann. Rheum. Dis. 81: 1453-1464, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35868845/&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;35868845&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/annrheumdis-2022-222629&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="35868845">Kozycki et al. (2022)</a> reported molecular findings in 21 patients from 13 unrelated families with ROSAH. Twenty of the patients were heterozygous for the recurrent T237M mutation in the ALPK1 gene, and 1 patient (patient 13.1) was heterozygous for a Y254C mutation (<a href="/entry/607347#0002">607347.0002</a>). In in vitro studies, <a href="#1" class="mim-tip-reference" title="Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others. &lt;strong&gt;Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.&lt;/strong&gt; Ann. Rheum. Dis. 81: 1453-1464, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35868845/&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;35868845&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/annrheumdis-2022-222629&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="35868845">Kozycki et al. (2022)</a> found that both mutations resulted in increased NF-kappa-B (see <a href="/entry/164011">164011</a>) signaling and STAT1 (<a href="/entry/600555">600555</a>) phosphorylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35868845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Kozycki2022" class="mim-anchor"></a>
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<p class="mim-text-font">
Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others.
<strong>Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.</strong>
Ann. Rheum. Dis. 81: 1453-1464, 2022.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35868845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35868845</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35868845" 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/annrheumdis-2022-222629" target="_blank">Full Text</a>]
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<a id="Tantravahi2012" class="mim-anchor"></a>
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Tantravahi, S. K., Williams, L. B., Digre, K. B., Creel, D. J., Smock, K. J., DeAngelis, M. M., Clayton, F. C., Vitale, A. T., Rodgers, G. M.
<strong>An inherited disorder with splenomegaly, cytopenias, and vision loss.</strong>
Am. J. Med. Genet. 158A: 475-481, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22307799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22307799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22307799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22307799" 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.34437" target="_blank">Full Text</a>]
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<a id="Williams2019" class="mim-anchor"></a>
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<p class="mim-text-font">
Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others.
<strong>ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.</strong>
Genet. Med. 21: 2103-2115, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30967659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30967659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30967659[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30967659" 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/s41436-019-0476-3" target="_blank">Full Text</a>]
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<a id="Zhong2020" class="mim-anchor"></a>
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Zhong, L., Wang, J., Wang, W., Wang, L., Quan, M., Tang, X., Gou, L., Wei, M., Xiao, J., Zhang, T., Sui, R., Zhou, Q., Song, H.
<strong>Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1.</strong>
J. Clin. Immun. 40: 350-358, 2020.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31939038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31939038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31939038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10875-020-00741-6" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 09/01/2023
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Marla J. F. O'Neill - updated : 10/28/2020
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Marla J. F. O&#x27;Neill : 12/10/2012
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alopez : 09/01/2023
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alopez : 10/28/2020<br>carol : 12/19/2012
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<strong>#</strong> 614979
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RETINAL DYSTROPHY, OPTIC NERVE EDEMA, SPLENOMEGALY, ANHIDROSIS, AND MIGRAINE HEADACHE SYNDROME; ROSAH
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<em>Alternative titles; symbols</em>
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SPLENOMEGALY, CYTOPENIA, AND VISION LOSS
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<strong>SNOMEDCT:</strong> 771471002; &nbsp;
<strong>ORPHA:</strong> 313800; &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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4q25
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ROSAH syndrome
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614979
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Autosomal dominant
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3
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ALPK1
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607347
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) is caused by heterozygous mutation in the ALPK1 gene (607347) on chromosome 4q25.</p>
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<strong>Description</strong>
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<p>Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) is an autosomal dominant disorder in which affected individuals present in childhood with reduced vision associated with papilledema and low-grade ocular inflammation. Progressive deterioration of visual acuity results in counting fingers to no light perception by the third decade of life. Patients also show anhidrosis, as well as splenomegaly and mild pancytopenia, and most experience headaches that may be migraine-like in nature (Williams et al., 2019). </p>
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<strong>Clinical Features</strong>
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<p>Tantravahi et al. (2012) studied a mother and 2 daughters, who were half-sisters, who had massive splenomegaly, cytopenia, anhidrosis, chronic optic nerve edema, and vision loss. The patients presented in the first decade of life with chronic optic nerve edema followed by slowly progressive vision loss, particularly central, and loss of color vision. In all cases, despite continued optic nerve head edema, lumbar puncture did not show elevated pressure. Although uveitis was seen in 2 patients, it was not present at all exams and testing for common causes of uveitis was negative. Disease progression was similar to a cone or cone-rod dystrophy, with electroretinography (ERG) showing loss of photopic (cone) responses with maintenance of scotopic (rod) responses into the teenage years in 2 patients; however, by ages 15 years to early twenties, all 3 patients had completely extinguished full-field ERGs. In addition, splenomegaly and mild pancytopenia developed in all 3 patients, at ages 9, 12, and 15 years; bone marrow evaluations were normal and splenectomy normalized their complete blood count values, indicating that the cytopenias were due to splenic sequestration. Splenic pathology showed congestion without infiltration or extramedullary hematopoiesis. Both daughters also reported migraine headaches and anhidrosis, and 1 also had episodic urticaria. Immunologic and autoimmune evaluations were negative. </p><p>Williams et al. (2019) restudied the family from Utah (family 1) with splenomegaly, cytopenia, and vision loss that was originally reported by Tantravahi et al. (2012), and ascertained 5 more similarly affected families, including 1 family from Australia (family 2), 1 from the Netherlands (family 3), 1 from Virginia (family 4), and 1 from Delaware (family 5). In the 16 affected individuals, the most frequent earliest feature was decreased vision associated with optic nerve edema, evident as early as 4 years of age and present by age 12 years in all cases. Low-grade ocular inflammation, unresponsive to steroids or other forms of immunosuppression, was common in affected individuals. In later childhood or in the second decade of life, patients had increasing visual impairment, with abnormal cone function and later loss of rod function in most. By the third decade of life, visual dysfunction was severe with visual acuity ranging from counting fingers to no light perception. In addition to the ocular findings, patients generally had splenomegaly, beginning in the first or second decade of life; 1 patient underwent splenectomy. Hematologic assessment showed chronic mild pancytopenia, which was sometimes exacerbated during periods of viral or other infection. Peripheral smears frequently showed leukopenia with reactive lymphocytosis; bone marrow was normocellular with trilineage hematopoiesis and relative erythroid hyperplasia. Affected individuals also experienced anhidrosis, and migrainous headache was a frequent feature, often associated with episodic fever and back pain. Mild renal impairment was present in some members of family 2, but was not a consistent feature in all patients. Williams et al. (2019) designated the disorder 'ROSAH syndrome' based on the retinopathy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache observed in these patients. </p><p>Zhong et al. (2020) described 2 unrelated Chinese girls with ROSAH syndrome. In addition to retinal dystrophy, papilledema, splenomegaly, and pancytopenia, both experienced intermittent febrile episodes and were anhidrotic. One patient had undergone elective splenectomy due to concerns about spontaneous rupture, and splenectomy was planned in the other patient. </p><p>Kozycki et al. (2022) reported clinical features in 27 patients with ROSAH syndrome. Almost all patients had inflammatory features, including fever, malaise, episodic abdominal pain, headache, cytopenia, and/or retinal vasculitis. Ophthalmologic findings in the cohort included optic nerve elevation, uveitis, retinal vasculitis, and retinal degeneration. Twenty patients had arthralgias, which started in childhood in some patients. Fourteen patients had gastrointestinal symptoms, including pain, gastroesophageal reflux, dysphagia, and/or reflux. Thirteen patients had recurrent headaches, and 7 patients had brain abnormalities seen on brain MRI, including calcification of the globi pallidi, red nucleus, and substantia nigra. Dental abnormalities included multiple caries in 23 patients and enamel defects in 7 patients; 5 patients were edentulous. Almost all patients had hyperhidrosis or anhidrosis, and 4 parous women had dysfunctional breast milk production. Laboratory findings included variably elevated C-reactive protein (CRP; 123260), transient neutropenia, and cytopenias. </p>
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<p>Kozycki et al. (2022) reported that 7 of 10 patients with ROSAH syndrome treated with anticytokine therapy had subjective improvement in 1 or more clinical symptoms. </p>
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<p>The transmission pattern of ROSAH in the family reported by Tantravahi et al. (2012) was consistent with autosomal dominant inheritance. Genetic analysis by Williams et al. (2019) confirmed autosomal dominant inheritance in this family; Williams et al. (2019) also showed that the mutation occurred de novo in the mother. The heterozygous mutations in other patients reported by Williams et al. (2019) and Zhong et al. (2020) occurred de novo. </p>
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<strong>Molecular Genetics</strong>
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<p>In all 16 patients from 5 unrelated families with ROSAH syndrome, Williams et al. (2019) identified heterozygosity for the same missense mutation in the ALPK1 gene (T237M; 607347.0001). The mutation segregated with disease in all families and was not found in the gnomAD database. </p><p>In 2 unrelated Chinese girls with ROSAH syndrome, Zhong et al. (2020) identified heterozygosity for the previously reported recurrent T237M mutation in the ALPK1 gene. The mutation arose de novo in both probands. </p><p>Kozycki et al. (2022) reported molecular findings in 21 patients from 13 unrelated families with ROSAH. Twenty of the patients were heterozygous for the recurrent T237M mutation in the ALPK1 gene, and 1 patient (patient 13.1) was heterozygous for a Y254C mutation (607347.0002). In in vitro studies, Kozycki et al. (2022) found that both mutations resulted in increased NF-kappa-B (see 164011) signaling and STAT1 (600555) phosphorylation. </p>
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<strong>REFERENCES</strong>
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Kozycki, C. T., Kodati, S., Huryn, L., Wang, H., Warner, B. M., Jani, P., Hammoud, D., Abu-Asab, M. S., Jittayasothorn, Y., Mattapallil, M. J., Tsai, W. L., Ullah, E., and 59 others.
<strong>Gain-of-function mutations in ALPK1 cause an NF-kappaB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.</strong>
Ann. Rheum. Dis. 81: 1453-1464, 2022.
[PubMed: 35868845]
[Full Text: https://doi.org/10.1136/annrheumdis-2022-222629]
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Tantravahi, S. K., Williams, L. B., Digre, K. B., Creel, D. J., Smock, K. J., DeAngelis, M. M., Clayton, F. C., Vitale, A. T., Rodgers, G. M.
<strong>An inherited disorder with splenomegaly, cytopenias, and vision loss.</strong>
Am. J. Med. Genet. 158A: 475-481, 2012.
[PubMed: 22307799]
[Full Text: https://doi.org/10.1002/ajmg.a.34437]
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Williams, L. B., Javed, A., Sabri, A., Morgan, D. J., Huff, C. D., Grigg, J. R., Heng, X. T., Khng, A. J., Hollink, I. H. I. M., Morrison, M. A., Owen, L. A., Anderson, K., and 29 others.
<strong>ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.</strong>
Genet. Med. 21: 2103-2115, 2019.
[PubMed: 30967659]
[Full Text: https://doi.org/10.1038/s41436-019-0476-3]
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Zhong, L., Wang, J., Wang, W., Wang, L., Quan, M., Tang, X., Gou, L., Wei, M., Xiao, J., Zhang, T., Sui, R., Zhou, Q., Song, H.
<strong>Juvenile onset splenomegaly and oculopathy due to germline mutation in ALPK1.</strong>
J. Clin. Immun. 40: 350-358, 2020.
[PubMed: 31939038]
[Full Text: https://doi.org/10.1007/s10875-020-00741-6]
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Hilary J. Vernon - updated : 09/01/2023<br>Marla J. F. O&#x27;Neill - updated : 10/28/2020
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Marla J. F. O&#x27;Neill : 12/10/2012
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alopez : 09/01/2023<br>alopez : 10/28/2020<br>carol : 12/19/2012
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