2584 lines
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Entry
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- #615722 - BOSCH-BOONSTRA-SCHAAF OPTIC ATROPHY SYNDROME; BBSOAS
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- OMIM
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<p>
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<span class="h4">#615722</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<li role="presentation">
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<a href="/clinicalSynopsis/615722"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<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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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div><a href="https://clinicaltrials.gov/search?cond=BOSCH-BOONSTRA-SCHAAF OPTIC ATROPHY SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=22827&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK587319/" 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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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615722[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=401777" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/62ab3ca7-2dcf-458e-98b6-c443aabed038/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0112226" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/615722" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0112226" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 770723007<br />
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<strong>ORPHA:</strong> 401777<br />
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<strong>DO:</strong> 0112226<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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615722
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</span>
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</span>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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BOSCH-BOONSTRA-SCHAAF OPTIC ATROPHY SYNDROME; BBSOAS
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/5/325?start=-3&limit=10&highlight=325">
|
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5q15
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Bosch-Boonstra-Schaaf optic atrophy syndrome
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615722"> 615722 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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NR2F1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/132890"> 132890 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/615722" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/615722" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/615722" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
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<p />
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<em> Face </em>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
|
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|
|
- Dysmorphic features, variable, nonspecific <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810453</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253978002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253978002</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Ears </em>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
|
- Hearing loss (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C3887873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887873</a>, <a href="https://bioportal.bioontology.org/search?q=C2029884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2029884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br />
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|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pale optic discs <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 /> -
|
|
Small optic discs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/423389004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">423389004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1828214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1828214</a>]</span><br /> -
|
|
Large optic discs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3810364&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3810364</a>]</span><br /> -
|
|
Excavation of optic discs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12451000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12451000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3805910&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3805910</a>]</span><br /> -
|
|
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
|
|
Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
|
|
Alacrima <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253215004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253215004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0344505&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0344505</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000522" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000522</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000522" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000522</a>]</span><br /> -
|
|
Decreased visual acuity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13164000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234632&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234632</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span><br /> -
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|
Visual field defects <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12184005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12184005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/368.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887875&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887875</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001123</a>]</span><br /> -
|
|
Visual impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246635007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246635007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397540003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042798</a>, <a href="https://bioportal.bioontology.org/search?q=C3665347&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665347</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span><br /> -
|
|
Small optic nerve <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5563170&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5563170</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> SKELETAL </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Hands </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Tapering fingers <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249768009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249768009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001182" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001182</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001182" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001182</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Delayed development <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Impaired intellectual development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4747273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4747273</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
|
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Thin corpus callosum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5441562&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441562</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033725</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033725" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033725</a>]</span><br /> -
|
|
Oromotor dysfunction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3281086&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3281086</a>]</span><br /> -
|
|
Speech problems <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267095009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267095009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0395016&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0395016</a>]</span><br /> -
|
|
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
|
|
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Seizures (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Behavioral Psychiatric Manifestations </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Autistic features (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846135&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846135</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000729" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000729</a>]</span><br /> -
|
|
ADHD (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7461003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7461003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/406506008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">406506008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F90</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F90.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F90.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/314.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314.01</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/314" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/314.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">314.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1263846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1263846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000752" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000752</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0007018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007018</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007018</a>]</span><br /> -
|
|
Increased pain tolerance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276613&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276613</a>]</span><br /> -
|
|
Sleep difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301345002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301345002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235162&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235162</a>]</span><br /> -
|
|
Touch sensitivity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5563169&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5563169</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<div>
|
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<span class="mim-font">
|
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|
|
- Variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> MOLECULAR BASIS </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the nuclear receptor subfamily 2, group F, member 1 gene (NR2F1, <a href="/entry/132890#0001">132890.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
|
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is caused by heterozygous mutation in the NR2F1 gene (<a href="/entry/132890">132890</a>) on chromosome 5q15.</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disorder characterized by delayed development, moderately impaired intellectual development, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by <a href="#2" class="mim-tip-reference" title="Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others. <strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong> Am. J. Hum. Genet. 94: 303-309, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24462372">Bosch et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24462372" 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="#2" class="mim-tip-reference" title="Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others. <strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong> Am. J. Hum. Genet. 94: 303-309, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24462372">Bosch et al. (2014)</a> reported 6 unrelated patients with optic nerve atrophy associated with developmental delay and impaired intellectual development (IQ range, 48-74). The patients ranged in age from 2 to 35 years. All had decreased visual acuity, often with visual field defects. Ophthalmologic examination showed variable optic disc abnormalities, including small discs, pale discs, and disc excavation. Five of the patients reportedly had cerebral visual impairment. Other ocular anomalies included strabismus and latent nystagmus. All patients had variable dysmorphic features, but there was no constant pattern. Dysmorphic features included protruding ears, helical anomalies, small nasal ridge, high nasal bridge, upturned nose, epicanthal folds, upslanting palpebral fissures, and tapering fingers. Two patients had hypotonia, and 1 adult patient had severe obsessive-compulsive disorder and autistic features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24462372" 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="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> described clinical features in 20 patients, aged 2 to 43 years, with BBSOAS. Nineteen of the 20 patients had impaired intellectual development or developmental delay, 15 had optic nerve atrophy, 15 had hypotonia, 12 had oromotor dysfunction, 8 had repetitive behavior, 7 had autism spectrum disorder, 8 had seizures, 5 had attention deficit-hyperactivity disorder (ADHD), 4 had a hearing defect, and 1 had spasticity. On brain MRI, 8 of 15 patients had a thin corpus callosum. Some individuals had mild dysmorphic features, but they did not appear to be consistent between individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26986877" 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="Martin-Hernandez, E., Rodriguez-Garcia, M. E., Chen, C.-A., Cotrina-Vinagre, F. J., Carnicero-Rodriguez, P., Bellusci, M., Schaaf, C. P., Martinez-Azorin, F. <strong>Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NRF2F1 gene mutation.</strong> J. Hum. Genet. 63: 525-528, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29410510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29410510</a>] [<a href="https://doi.org/10.1038/s10038-017-0398-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29410510">Martin-Hernandez et al. (2018)</a> reported a 17-year-old Spanish patient who presented at 6 months of age with vomiting, hypotonia, impaired consciousness, and strabismus. Laboratory studies showed an elevated creatine kinase. EMG showed myopathic signs. Brain MRI showed a hypoplastic corpus callosum, and EEG was normal. At 7 months of age she presented with right-sided hemiparesis and had a normal EEG. Respiratory chain analysis in a skeletal muscle biopsy showed a deficiency of complex IV. mtDNA sequencing was normal. Ophthalmologic examination at 20 months of age identified partial bilateral optic atrophy and abnormal visual-evoked potentials. MRI/MRS at age 12 years showed a slight lactate peak in the basal ganglia and a hypoplastic corpus callosum. At age 17 she had an IQ of 30-50 on the Stanford-Binet Scale. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29410510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Park, S. E., Lee, J. S., Lee, S.-T., Kim, H. Y., Han, S.-H., Han, J. <strong>Targeted panel sequencing identifies a novel NR2F1 mutations in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong> Ophthalmic Genet. 40: 359-361, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31393201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31393201</a>] [<a href="https://doi.org/10.1080/13816810.2019.1650074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31393201">Park et al. (2019)</a> reported a 7-year-old Korean boy with delayed motor development (particularly in the fine motor domain), borderline intellectual development, and ADHD. Ophthalmologic exam showed latent nystagmus, reduced visual acuity, optic atrophy and diffuse loss of retinal nerve fiber layers in both eyes. Brain MRI showed thinning of the posterior corpus callosum. Facial features included retrognathia and external ear protrusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31393201" 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="Bojanek, E. K., Mosconi, M. W., Guter, S., Betancur, C., Macmillan, C., Cook, E. H. <strong>Clinical and neurocognitive issues associated with Bosch-Boonstra-Schaaf optic atrophy syndrome: a case study.</strong> Am. J. Med. Genet. 182A: 213-218, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31729143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31729143</a>] [<a href="https://doi.org/10.1002/ajmg.a.61409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31729143">Bojanek et al. (2020)</a> reported a 30-year-old man with optic nerve hypoplasia, no developmental delay, superior verbal abilities, and reduced nonverbal abilities. After birth, he had hyperbilirubinemia and was treated with phototherapy. At age 3 years, he was diagnosed with pervasive developmental disorder and ADHD. At age 8 he was diagnosed with a nonverbal learning disability, and at age 23 he was diagnosed with autism spectrum disorder. He graduated from college, maintained employment, and lived alone with support. On examination at age 30, he had generalized joint hyperextensibility, bilateral ear cupping, midface hypoplasia, a flat nasal tip, and prominent lips. MRI showed decreased size of the right optic nerve intraocular segment, and OCT testing showed retinal nerve fiber layer thinning. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31729143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Walsh, S., Gosswein, S. S., Rump, A., von der Hagen, M., Hackmann, K., Schrock, E., Di Donato, N., Kahlert, A.-K. <strong>Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong> Europ. J. Med. Genet. 63: 104019, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712214</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32712214">Walsh et al. (2020)</a> described a boy who was born prematurely to a pregnancy complicated by polyhydramnios. Developmental delay was noted at 8 months of age. At age 2.5 years, he developed myoclonic-astatic seizures. He developed nystagmus and hyperopia, and had severe reduction in vision. At age 6 years, he was found to have unilateral conductive hearing loss. At age 5 years, he developed a cervicothoracic syringomyelia. A brain MRI at age 7 years showed hypoplasia of the optic nerve and optic chiasm and a hypoplastic corpus callosum. He was diagnosed with an autism spectrum disorder. At age 9 years and 10 months, he had macrocephaly, a broad forehead, strabismus and small, low-set ears. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Rech, M. E., McCarthy, J. M., Chen, C.-A., Edmond, J. C., Shah, V. S., Bosch, D. G. M., Berry, G. T., Williams, L., Madan-Khetarpal, S., Niyazov, D., Shaw-Smith, C., Kovar, E. M., Lupo, P. J., Schaaf, C. P. <strong>Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.</strong> Am. J. Med. Genet. 182A: 1426-1437, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275123</a>] [<a href="https://doi.org/10.1002/ajmg.a.61580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275123">Rech et al. (2020)</a> described clinical features in 18 new patients, provided updated data on 9 previously reported patients, and reviewed an additional 27 patients reported in the literature with BBSOAS. The most common clinical features were developmental delay, speech delay, vision impairment, and hypotonia, all of which were present in at least 89% of patients for whom information was available. Autism spectrum was seen in 80% of patients, cognitive/behavioral features in 78%, oromotor dysfunction in 70%, and mouth stuffing in 84%. General vision impairment was reported in 47 of 52 patients, optic atrophy or optic disc pallor in 41 of 50 patients, and alacrima in 21 of 27 patients; 27 of 40 patients had cortical visual impairment, 19 of 39 had optic nerve hypoplasia or a small optic nerve, and 15 of 29 had latent nystagmus or fusional maldevelopment. Additional behavioral characteristics included love of music (present in 100% of patients surveyed), unusually good long-term memory (76%), high pain tolerance (78%), sleep difficulties (61%), and touch sensitivity (59%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275123" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Starosta, R. T., Tarnowski, J., Vairo, F. P. E., Raymond, K., Preston, G., Morava, E. <strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: functional evidence for benignity of the ALG6 c.391T-C (p.Tyr131His) variant and further expanding the BBSOAS phenotype.</strong> Europ. J. Med. Genet. 63: 103941, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32407885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32407885</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32407885">Starosta et al. (2020)</a> reported a 31-year old female with BBSOAS who had previously been diagnosed with congenital disorder of glycosylation type 1c (<a href="/entry/603147">603147</a>) based on transferrin isoelectrofocusing and identification of a mutation in the ALG6 gene (<a href="/entry/604566#0007">604566.0007</a>) by targeted genetic testing. The ALG6 variant was later reclassified as a variant of unknown significance. By whole-exome sequencing, <a href="#7" class="mim-tip-reference" title="Starosta, R. T., Tarnowski, J., Vairo, F. P. E., Raymond, K., Preston, G., Morava, E. <strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: functional evidence for benignity of the ALG6 c.391T-C (p.Tyr131His) variant and further expanding the BBSOAS phenotype.</strong> Europ. J. Med. Genet. 63: 103941, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32407885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32407885</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32407885">Starosta et al. (2020)</a> identified a previously reported heterozygous mutation in the NR2F1 gene. The patient had typical features of BBSOAS including dysmorphic facies, hypotonia, developmental delay, seizures, and progressive visual impairment with optic atrophy. In addition, the patient had protein-losing enteropathy and ataxia, possibly extending the phenotype of BBSOAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32407885" 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 heterozygous mutations in the N2RF1 gene identified in patients with BBSOAS by <a href="#2" class="mim-tip-reference" title="Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others. <strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong> Am. J. Hum. Genet. 94: 303-309, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24462372">Bosch et al. (2014)</a> and <a href="#3" class="mim-tip-reference" title="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26986877+24462372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 patients with BBSOAS, <a href="#2" class="mim-tip-reference" title="Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others. <strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong> Am. J. Hum. Genet. 94: 303-309, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24462372">Bosch et al. (2014)</a> identified heterozygous deletions of chromosome 5q (0.83 Mb and 2.85 Mb, respectively) encompassing the NR2F1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24462372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 patients with BBSOAS, including an affected father and son (individuals 17 and 18, respectively), <a href="#3" class="mim-tip-reference" title="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> identified heterozygous deletions on chromosome 5, ranging from 0.2 to 5.0 Mb and encompassing the NR2F1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26986877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 4 patients with cortical visual impairment and intellectual disability, <a href="#2" class="mim-tip-reference" title="Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others. <strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong> Am. J. Hum. Genet. 94: 303-309, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24462372">Bosch et al. (2014)</a> identified 4 different de novo heterozygous missense mutations in the NR2F1 gene (<a href="/entry/132890#0001">132890.0001</a>-<a href="/entry/132890#0004">132890.0004</a>). In vitro functional expression assays with a luciferase reporter in HEK293 cells showed that all the missense mutations had significantly decreased transcriptional activity compared to wildtype. The findings suggested haploinsufficiency as the pathogenetic mechanism for the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24462372" 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 15 patients with BBSOAS, <a href="#3" class="mim-tip-reference" title="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> identified 15 de novo heterozygous mutations in the NR2F1 gene, including 7 missense mutations, 5 mutations that disrupted translation initiation (see, e.g., <a href="/entry/132890#0005">132890.0005</a>), 2 indels resulting in a frameshift, and an in-frame indel. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing or by chromosome microarray analysis. Five of the missense mutations were located in the DNA-binding domain (DBD), 1 was located adjacent to the DBD domain, and 1 was located in the ligand-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26986877" 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="Martin-Hernandez, E., Rodriguez-Garcia, M. E., Chen, C.-A., Cotrina-Vinagre, F. J., Carnicero-Rodriguez, P., Bellusci, M., Schaaf, C. P., Martinez-Azorin, F. <strong>Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NRF2F1 gene mutation.</strong> J. Hum. Genet. 63: 525-528, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29410510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29410510</a>] [<a href="https://doi.org/10.1038/s10038-017-0398-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29410510">Martin-Hernandez et al. (2018)</a> identified a de novo heterozygous missense mutation in the DBD of the NR2F1 gene (K96E; <a href="/entry/132890#0006">132890.0006</a>) in a 17-year-old Spanish patient with BBSOAS. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29410510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 7-year-old Korean boy with BBSOAS, <a href="#5" class="mim-tip-reference" title="Park, S. E., Lee, J. S., Lee, S.-T., Kim, H. Y., Han, S.-H., Han, J. <strong>Targeted panel sequencing identifies a novel NR2F1 mutations in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong> Ophthalmic Genet. 40: 359-361, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31393201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31393201</a>] [<a href="https://doi.org/10.1080/13816810.2019.1650074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31393201">Park et al. (2019)</a> identified a heterozygous nonsense mutation in the NR2F1 gene (Y171X; <a href="/entry/132890#0007">132890.0007</a>). Parental testing was not performed. The mutation was identified by using a next-generation sequencing panel of 429 genes associated with hereditary optic neuropathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31393201" 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>By whole-exome sequencing in a 31-year-old woman diagnosed with BBSOAS, <a href="#7" class="mim-tip-reference" title="Starosta, R. T., Tarnowski, J., Vairo, F. P. E., Raymond, K., Preston, G., Morava, E. <strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: functional evidence for benignity of the ALG6 c.391T-C (p.Tyr131His) variant and further expanding the BBSOAS phenotype.</strong> Europ. J. Med. Genet. 63: 103941, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32407885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32407885</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.103941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32407885">Starosta et al. (2020)</a> identified heterozygosity for a de novo Y171X mutation in the NR2F1 gene. The patient had previously been reported with a diagnosis of congenital disorder of glycosylation type Ic (CDG1C; <a href="/entry/603147">603147</a>) and had a homozygous Y131H mutation in the ALG6 gene (<a href="/entry/604566#0007">604566.0007</a>), which was later reclassified as a variant of unknown significance based on its frequency in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32407885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 30-year-old man with BBSOAS, <a href="#1" class="mim-tip-reference" title="Bojanek, E. K., Mosconi, M. W., Guter, S., Betancur, C., Macmillan, C., Cook, E. H. <strong>Clinical and neurocognitive issues associated with Bosch-Boonstra-Schaaf optic atrophy syndrome: a case study.</strong> Am. J. Med. Genet. 182A: 213-218, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31729143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31729143</a>] [<a href="https://doi.org/10.1002/ajmg.a.61409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31729143">Bojanek et al. (2020)</a> identified a de novo heterozygous nonsense mutation in the NR2F1 gene (Q28X; <a href="/entry/132890#0008">132890.0008</a>). The mutation was identified by trio whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31729143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a boy with severe BBSOAS, <a href="#8" class="mim-tip-reference" title="Walsh, S., Gosswein, S. S., Rump, A., von der Hagen, M., Hackmann, K., Schrock, E., Di Donato, N., Kahlert, A.-K. <strong>Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong> Europ. J. Med. Genet. 63: 104019, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712214</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32712214">Walsh et al. (2020)</a> identified a de novo heterozygous frameshift mutation in the LBD of the NR2F1 gene (c.1080del; <a href="/entry/132890#0009">132890.0009</a>). Because the mutation occurred in the last exon of N2RF1, <a href="#8" class="mim-tip-reference" title="Walsh, S., Gosswein, S. S., Rump, A., von der Hagen, M., Hackmann, K., Schrock, E., Di Donato, N., Kahlert, A.-K. <strong>Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong> Europ. J. Med. Genet. 63: 104019, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712214</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32712214">Walsh et al. (2020)</a> speculated that the resultant mRNA might not be subject to nonsense-mediated decay, raising the question of whether there may be a dominant-negative effect in this case as has been considered for missense mutations affecting the DBD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712214" 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="#3" class="mim-tip-reference" title="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> assessed molecular and clinical features in 20 patients with BBSOAS. The 5 patients with microdeletions encompassing the NR2F1 gene had a lower prevalence of several clinical features when compared to 5 patients with missense mutations that completely abolish transcriptional activity, including hypotonia, oromotor dysfunction, thin corpus callosum, repetitive behaviors, autism spectrum disorder, seizures, and hearing defects. These findings led <a href="#3" class="mim-tip-reference" title="Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others. <strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong> Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>] [<a href="https://doi.org/10.1038/gim.2016.18" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26986877">Chen et al. (2016)</a> to consider whether a dominant-negative effect plays a role in BBSOAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26986877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Rech, M. E., McCarthy, J. M., Chen, C.-A., Edmond, J. C., Shah, V. S., Bosch, D. G. M., Berry, G. T., Williams, L., Madan-Khetarpal, S., Niyazov, D., Shaw-Smith, C., Kovar, E. M., Lupo, P. J., Schaaf, C. P. <strong>Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.</strong> Am. J. Med. Genet. 182A: 1426-1437, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275123</a>] [<a href="https://doi.org/10.1002/ajmg.a.61580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275123">Rech et al. (2020)</a> compared the prevalence of clinical features between 22 patients with BBSOAS and point mutations or in-frame deletions in the DNA-binding domain (DBD) of the NR2F gene and 32 patients with BBSOAS and whole-gene deletions, nonsense mutations, frameshift mutations, or point mutations outside of the DBD. <a href="#6" class="mim-tip-reference" title="Rech, M. E., McCarthy, J. M., Chen, C.-A., Edmond, J. C., Shah, V. S., Bosch, D. G. M., Berry, G. T., Williams, L., Madan-Khetarpal, S., Niyazov, D., Shaw-Smith, C., Kovar, E. M., Lupo, P. J., Schaaf, C. P. <strong>Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.</strong> Am. J. Med. Genet. 182A: 1426-1437, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275123</a>] [<a href="https://doi.org/10.1002/ajmg.a.61580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275123">Rech et al. (2020)</a> found that mutations in the DBD were associated with a higher prevalence of motor delay, the inability to walk unassisted, the absence of speech, seizures, and sensitivity to touch compared to other types of mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275123" 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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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31729143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31729143</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31729143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61409" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Bosch2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others.
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<strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong>
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Am. J. Hum. Genet. 94: 303-309, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24462372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24462372</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24462372[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=24462372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2014.01.002" target="_blank">Full Text</a>]
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<a id="Chen2016" class="mim-anchor"></a>
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<div class="">
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Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others.
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<strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong>
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Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26986877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26986877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26986877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/gim.2016.18" target="_blank">Full Text</a>]
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<a id="Martin-Hernandez2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Martin-Hernandez, E., Rodriguez-Garcia, M. E., Chen, C.-A., Cotrina-Vinagre, F. J., Carnicero-Rodriguez, P., Bellusci, M., Schaaf, C. P., Martinez-Azorin, F.
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<strong>Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NRF2F1 gene mutation.</strong>
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J. Hum. Genet. 63: 525-528, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29410510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29410510</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29410510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s10038-017-0398-3" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Park2019" class="mim-anchor"></a>
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<p class="mim-text-font">
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Park, S. E., Lee, J. S., Lee, S.-T., Kim, H. Y., Han, S.-H., Han, J.
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<strong>Targeted panel sequencing identifies a novel NR2F1 mutations in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong>
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Ophthalmic Genet. 40: 359-361, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31393201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31393201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31393201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1080/13816810.2019.1650074" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Rech2020" class="mim-anchor"></a>
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Rech, M. E., McCarthy, J. M., Chen, C.-A., Edmond, J. C., Shah, V. S., Bosch, D. G. M., Berry, G. T., Williams, L., Madan-Khetarpal, S., Niyazov, D., Shaw-Smith, C., Kovar, E. M., Lupo, P. J., Schaaf, C. P.
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<strong>Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.</strong>
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Am. J. Med. Genet. 182A: 1426-1437, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275123</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275123" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61580" target="_blank">Full Text</a>]
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<a id="Starosta2020" class="mim-anchor"></a>
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Starosta, R. T., Tarnowski, J., Vairo, F. P. E., Raymond, K., Preston, G., Morava, E.
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<strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: functional evidence for benignity of the ALG6 c.391T-C (p.Tyr131His) variant and further expanding the BBSOAS phenotype.</strong>
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Europ. J. Med. Genet. 63: 103941, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32407885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32407885</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32407885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.103941" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Walsh2020" class="mim-anchor"></a>
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Walsh, S., Gosswein, S. S., Rump, A., von der Hagen, M., Hackmann, K., Schrock, E., Di Donato, N., Kahlert, A.-K.
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<strong>Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong>
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Europ. J. Med. Genet. 63: 104019, 2020. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712214</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.104019" target="_blank">Full Text</a>]
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Sonja A. Rasmussen - updated : 07/28/2022
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Hilary J. Vernon - updated : 03/29/2021
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Creation Date:
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Cassandra L. Kniffin : 3/31/2014
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carol : 07/28/2022
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carol : 03/30/2021<br>carol : 03/29/2021<br>carol : 06/17/2015<br>carol : 7/8/2014<br>carol : 4/8/2014<br>ckniffin : 4/3/2014
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<strong>#</strong> 615722
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BOSCH-BOONSTRA-SCHAAF OPTIC ATROPHY SYNDROME; BBSOAS
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<strong>SNOMEDCT:</strong> 770723007;
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<strong>ORPHA:</strong> 401777;
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<strong>DO:</strong> 0112226;
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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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5q15
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Bosch-Boonstra-Schaaf optic atrophy syndrome
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615722
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Autosomal dominant
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3
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NR2F1
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132890
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is caused by heterozygous mutation in the NR2F1 gene (132890) on chromosome 5q15.</p>
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<strong>Description</strong>
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<p>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disorder characterized by delayed development, moderately impaired intellectual development, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by Bosch et al., 2014). </p>
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<strong>Clinical Features</strong>
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<p>Bosch et al. (2014) reported 6 unrelated patients with optic nerve atrophy associated with developmental delay and impaired intellectual development (IQ range, 48-74). The patients ranged in age from 2 to 35 years. All had decreased visual acuity, often with visual field defects. Ophthalmologic examination showed variable optic disc abnormalities, including small discs, pale discs, and disc excavation. Five of the patients reportedly had cerebral visual impairment. Other ocular anomalies included strabismus and latent nystagmus. All patients had variable dysmorphic features, but there was no constant pattern. Dysmorphic features included protruding ears, helical anomalies, small nasal ridge, high nasal bridge, upturned nose, epicanthal folds, upslanting palpebral fissures, and tapering fingers. Two patients had hypotonia, and 1 adult patient had severe obsessive-compulsive disorder and autistic features. </p><p>Chen et al. (2016) described clinical features in 20 patients, aged 2 to 43 years, with BBSOAS. Nineteen of the 20 patients had impaired intellectual development or developmental delay, 15 had optic nerve atrophy, 15 had hypotonia, 12 had oromotor dysfunction, 8 had repetitive behavior, 7 had autism spectrum disorder, 8 had seizures, 5 had attention deficit-hyperactivity disorder (ADHD), 4 had a hearing defect, and 1 had spasticity. On brain MRI, 8 of 15 patients had a thin corpus callosum. Some individuals had mild dysmorphic features, but they did not appear to be consistent between individuals. </p><p>Martin-Hernandez et al. (2018) reported a 17-year-old Spanish patient who presented at 6 months of age with vomiting, hypotonia, impaired consciousness, and strabismus. Laboratory studies showed an elevated creatine kinase. EMG showed myopathic signs. Brain MRI showed a hypoplastic corpus callosum, and EEG was normal. At 7 months of age she presented with right-sided hemiparesis and had a normal EEG. Respiratory chain analysis in a skeletal muscle biopsy showed a deficiency of complex IV. mtDNA sequencing was normal. Ophthalmologic examination at 20 months of age identified partial bilateral optic atrophy and abnormal visual-evoked potentials. MRI/MRS at age 12 years showed a slight lactate peak in the basal ganglia and a hypoplastic corpus callosum. At age 17 she had an IQ of 30-50 on the Stanford-Binet Scale. </p><p>Park et al. (2019) reported a 7-year-old Korean boy with delayed motor development (particularly in the fine motor domain), borderline intellectual development, and ADHD. Ophthalmologic exam showed latent nystagmus, reduced visual acuity, optic atrophy and diffuse loss of retinal nerve fiber layers in both eyes. Brain MRI showed thinning of the posterior corpus callosum. Facial features included retrognathia and external ear protrusion. </p><p>Bojanek et al. (2020) reported a 30-year-old man with optic nerve hypoplasia, no developmental delay, superior verbal abilities, and reduced nonverbal abilities. After birth, he had hyperbilirubinemia and was treated with phototherapy. At age 3 years, he was diagnosed with pervasive developmental disorder and ADHD. At age 8 he was diagnosed with a nonverbal learning disability, and at age 23 he was diagnosed with autism spectrum disorder. He graduated from college, maintained employment, and lived alone with support. On examination at age 30, he had generalized joint hyperextensibility, bilateral ear cupping, midface hypoplasia, a flat nasal tip, and prominent lips. MRI showed decreased size of the right optic nerve intraocular segment, and OCT testing showed retinal nerve fiber layer thinning. </p><p>Walsh et al. (2020) described a boy who was born prematurely to a pregnancy complicated by polyhydramnios. Developmental delay was noted at 8 months of age. At age 2.5 years, he developed myoclonic-astatic seizures. He developed nystagmus and hyperopia, and had severe reduction in vision. At age 6 years, he was found to have unilateral conductive hearing loss. At age 5 years, he developed a cervicothoracic syringomyelia. A brain MRI at age 7 years showed hypoplasia of the optic nerve and optic chiasm and a hypoplastic corpus callosum. He was diagnosed with an autism spectrum disorder. At age 9 years and 10 months, he had macrocephaly, a broad forehead, strabismus and small, low-set ears. </p><p>Rech et al. (2020) described clinical features in 18 new patients, provided updated data on 9 previously reported patients, and reviewed an additional 27 patients reported in the literature with BBSOAS. The most common clinical features were developmental delay, speech delay, vision impairment, and hypotonia, all of which were present in at least 89% of patients for whom information was available. Autism spectrum was seen in 80% of patients, cognitive/behavioral features in 78%, oromotor dysfunction in 70%, and mouth stuffing in 84%. General vision impairment was reported in 47 of 52 patients, optic atrophy or optic disc pallor in 41 of 50 patients, and alacrima in 21 of 27 patients; 27 of 40 patients had cortical visual impairment, 19 of 39 had optic nerve hypoplasia or a small optic nerve, and 15 of 29 had latent nystagmus or fusional maldevelopment. Additional behavioral characteristics included love of music (present in 100% of patients surveyed), unusually good long-term memory (76%), high pain tolerance (78%), sleep difficulties (61%), and touch sensitivity (59%). </p><p>Starosta et al. (2020) reported a 31-year old female with BBSOAS who had previously been diagnosed with congenital disorder of glycosylation type 1c (603147) based on transferrin isoelectrofocusing and identification of a mutation in the ALG6 gene (604566.0007) by targeted genetic testing. The ALG6 variant was later reclassified as a variant of unknown significance. By whole-exome sequencing, Starosta et al. (2020) identified a previously reported heterozygous mutation in the NR2F1 gene. The patient had typical features of BBSOAS including dysmorphic facies, hypotonia, developmental delay, seizures, and progressive visual impairment with optic atrophy. In addition, the patient had protein-losing enteropathy and ataxia, possibly extending the phenotype of BBSOAS. </p>
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<p>The heterozygous mutations in the N2RF1 gene identified in patients with BBSOAS by Bosch et al. (2014) and Chen et al. (2016) occurred de novo. </p>
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<p>In 2 patients with BBSOAS, Bosch et al. (2014) identified heterozygous deletions of chromosome 5q (0.83 Mb and 2.85 Mb, respectively) encompassing the NR2F1 gene. </p><p>In 5 patients with BBSOAS, including an affected father and son (individuals 17 and 18, respectively), Chen et al. (2016) identified heterozygous deletions on chromosome 5, ranging from 0.2 to 5.0 Mb and encompassing the NR2F1 gene. </p>
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<p>In 4 patients with cortical visual impairment and intellectual disability, Bosch et al. (2014) identified 4 different de novo heterozygous missense mutations in the NR2F1 gene (132890.0001-132890.0004). In vitro functional expression assays with a luciferase reporter in HEK293 cells showed that all the missense mutations had significantly decreased transcriptional activity compared to wildtype. The findings suggested haploinsufficiency as the pathogenetic mechanism for the disorder. </p><p>In 15 patients with BBSOAS, Chen et al. (2016) identified 15 de novo heterozygous mutations in the NR2F1 gene, including 7 missense mutations, 5 mutations that disrupted translation initiation (see, e.g., 132890.0005), 2 indels resulting in a frameshift, and an in-frame indel. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing or by chromosome microarray analysis. Five of the missense mutations were located in the DNA-binding domain (DBD), 1 was located adjacent to the DBD domain, and 1 was located in the ligand-binding domain. </p><p>Martin-Hernandez et al. (2018) identified a de novo heterozygous missense mutation in the DBD of the NR2F1 gene (K96E; 132890.0006) in a 17-year-old Spanish patient with BBSOAS. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. </p><p>In a 7-year-old Korean boy with BBSOAS, Park et al. (2019) identified a heterozygous nonsense mutation in the NR2F1 gene (Y171X; 132890.0007). Parental testing was not performed. The mutation was identified by using a next-generation sequencing panel of 429 genes associated with hereditary optic neuropathy. </p><p>By whole-exome sequencing in a 31-year-old woman diagnosed with BBSOAS, Starosta et al. (2020) identified heterozygosity for a de novo Y171X mutation in the NR2F1 gene. The patient had previously been reported with a diagnosis of congenital disorder of glycosylation type Ic (CDG1C; 603147) and had a homozygous Y131H mutation in the ALG6 gene (604566.0007), which was later reclassified as a variant of unknown significance based on its frequency in the gnomAD database. </p><p>In a 30-year-old man with BBSOAS, Bojanek et al. (2020) identified a de novo heterozygous nonsense mutation in the NR2F1 gene (Q28X; 132890.0008). The mutation was identified by trio whole-exome sequencing. </p><p>In a boy with severe BBSOAS, Walsh et al. (2020) identified a de novo heterozygous frameshift mutation in the LBD of the NR2F1 gene (c.1080del; 132890.0009). Because the mutation occurred in the last exon of N2RF1, Walsh et al. (2020) speculated that the resultant mRNA might not be subject to nonsense-mediated decay, raising the question of whether there may be a dominant-negative effect in this case as has been considered for missense mutations affecting the DBD. </p>
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<p>Chen et al. (2016) assessed molecular and clinical features in 20 patients with BBSOAS. The 5 patients with microdeletions encompassing the NR2F1 gene had a lower prevalence of several clinical features when compared to 5 patients with missense mutations that completely abolish transcriptional activity, including hypotonia, oromotor dysfunction, thin corpus callosum, repetitive behaviors, autism spectrum disorder, seizures, and hearing defects. These findings led Chen et al. (2016) to consider whether a dominant-negative effect plays a role in BBSOAS. </p><p>Rech et al. (2020) compared the prevalence of clinical features between 22 patients with BBSOAS and point mutations or in-frame deletions in the DNA-binding domain (DBD) of the NR2F gene and 32 patients with BBSOAS and whole-gene deletions, nonsense mutations, frameshift mutations, or point mutations outside of the DBD. Rech et al. (2020) found that mutations in the DBD were associated with a higher prevalence of motor delay, the inability to walk unassisted, the absence of speech, seizures, and sensitivity to touch compared to other types of mutations. </p>
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<strong>REFERENCES</strong>
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Bojanek, E. K., Mosconi, M. W., Guter, S., Betancur, C., Macmillan, C., Cook, E. H.
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<strong>Clinical and neurocognitive issues associated with Bosch-Boonstra-Schaaf optic atrophy syndrome: a case study.</strong>
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Am. J. Med. Genet. 182A: 213-218, 2020.
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[PubMed: 31729143]
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[Full Text: https://doi.org/10.1002/ajmg.a.61409]
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Bosch, D. G. M., Boonstra, F. N., Gonzaga-Jauregui, C., Xu, M., de Ligt, J., Jhangiani, S., Wiszniewski, W., Muzny, D. M., Yntema, H. G., Pfundt, R., Vissers, L. E. L. M., Spruijt, L., and 12 others.
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<strong>NR2F1 mutations cause optic atrophy with intellectual disability.</strong>
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Am. J. Hum. Genet. 94: 303-309, 2014.
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[PubMed: 24462372]
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[Full Text: https://doi.org/10.1016/j.ajhg.2014.01.002]
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Chen, C.-A., Bosch, D. G. M., Cho, M. T., Rosenfeld, J. A., Shinawi, M., Lewis, R. A., Mann, J., Jayakar, P., Payne, K., Walsh, L., Moss, T., Schreibr, A., and 23 others.
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<strong>The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.</strong>
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Genet. Med. 18: 1143-1150, 2016. Note: Erratum: Genet. Med. 19: 962 only, 2017.
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[PubMed: 26986877]
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[Full Text: https://doi.org/10.1038/gim.2016.18]
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Martin-Hernandez, E., Rodriguez-Garcia, M. E., Chen, C.-A., Cotrina-Vinagre, F. J., Carnicero-Rodriguez, P., Bellusci, M., Schaaf, C. P., Martinez-Azorin, F.
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<strong>Mitochondrial involvement in a Bosch-Boonstra-Schaaf optic atrophy syndrome patient with a novel de novo NRF2F1 gene mutation.</strong>
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J. Hum. Genet. 63: 525-528, 2018.
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[PubMed: 29410510]
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[Full Text: https://doi.org/10.1038/s10038-017-0398-3]
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Park, S. E., Lee, J. S., Lee, S.-T., Kim, H. Y., Han, S.-H., Han, J.
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<strong>Targeted panel sequencing identifies a novel NR2F1 mutations in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong>
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Ophthalmic Genet. 40: 359-361, 2019.
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[PubMed: 31393201]
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[Full Text: https://doi.org/10.1080/13816810.2019.1650074]
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Rech, M. E., McCarthy, J. M., Chen, C.-A., Edmond, J. C., Shah, V. S., Bosch, D. G. M., Berry, G. T., Williams, L., Madan-Khetarpal, S., Niyazov, D., Shaw-Smith, C., Kovar, E. M., Lupo, P. J., Schaaf, C. P.
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<strong>Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations.</strong>
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Am. J. Med. Genet. 182A: 1426-1437, 2020.
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[PubMed: 32275123]
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[Full Text: https://doi.org/10.1002/ajmg.a.61580]
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Starosta, R. T., Tarnowski, J., Vairo, F. P. E., Raymond, K., Preston, G., Morava, E.
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<strong>Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) initially diagnosed as ALG6-CDG: functional evidence for benignity of the ALG6 c.391T-C (p.Tyr131His) variant and further expanding the BBSOAS phenotype.</strong>
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Europ. J. Med. Genet. 63: 103941, 2020.
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[PubMed: 32407885]
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[Full Text: https://doi.org/10.1016/j.ejmg.2020.103941]
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Walsh, S., Gosswein, S. S., Rump, A., von der Hagen, M., Hackmann, K., Schrock, E., Di Donato, N., Kahlert, A.-K.
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<strong>Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome.</strong>
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Europ. J. Med. Genet. 63: 104019, 2020. Note: Electronic Article.
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[PubMed: 32712214]
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[Full Text: https://doi.org/10.1016/j.ejmg.2020.104019]
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Sonja A. Rasmussen - updated : 07/28/2022<br>Hilary J. Vernon - updated : 03/29/2021
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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