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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>CHD2-Related Neurodevelopmental Disorders - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="CHD2-Related Neurodevelopmental Disorders">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2021/01/21">
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<meta name="citation_author" content="Gemma L Carvill">
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<meta name="citation_author" content="Heather C Mefford">
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<meta name="citation_pmid" content="26677509">
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<meta name="citation_keywords" content="Chromodomain-helicase-DNA-binding protein 2">
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<meta name="citation_keywords" content="CHD2">
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<meta name="citation_keywords" content="CHD2-Related Neurodevelopmental Disorders">
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<meta name="DC.Title" content="CHD2-Related Neurodevelopmental Disorders">
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<meta name="DC.Contributor" content="Gemma L Carvill">
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<meta name="DC.Contributor" content="Heather C Mefford">
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<meta name="description" content="CHD2-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common.">
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<meta name="og:description" content="CHD2-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common.">
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class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK333201_"><span class="title" itemprop="name"><i>CHD2</i>-Related Neurodevelopmental Disorders</span></h1><p class="contribs">Carvill GL, Mefford HC.</p><p class="fm-aai"><a href="#_NBK333201_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 23 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="chd2-dis.Summary" itemprop="description"><h2 id="_chd2-dis_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>CHD2</i>-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of a <i>CHD2</i>-related neurodevelopmental disorder is established in a proband with suggestive findings and a heterozygous pathogenic variant in <i>CHD2</i> identified by molecular genetic testing.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Seizures should be managed by an experienced pediatric neurologist. At this time, no specific guidelines regarding choice of specific anti-seizure medications exist, as the best regimen for <i>CHD2</i>-related neurodevelopmental disorders is not yet established. Most Individuals remain refractory to treatment and require multiple anti-seizure medications. Support services for those with developmental delay, intellectual disability, and/or associated psychiatric/behavioral disorders.</p><p><i>Surveillance:</i> At each visit assess for new seizures or change in seizures; evaluate developmental progress and educational needs; behavioral assessment for anxiety, attention, and aggressive or self-injurious behavior; assess family need for social work support and care coordination.</p><p><i>Agents/circumstances to avoid:</i> Because clinical photosensitivity may result in injuries due to the consequences of induced seizures, it is recommended that stimuli that may provoke seizures (e.g., intensely flickering lights) be avoided.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>CHD2</i>-related neurodevelopmental disorders are autosomal dominant disorders typically caused by a <i>de novo</i> pathogenic variant. If the <i>CHD2</i> pathogenic variant identified in the proband is not identified in either parent, the risk to sibs is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the <i>CHD2</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p></div></div><div id="chd2-dis.Diagnosis"><h2 id="_chd2-dis_Diagnosis_">Diagnosis</h2><div id="chd2-dis.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>CHD2</i>-related neurodevelopmental disorders <b>should be suspected</b> in individuals with the following:</p><ul><li class="half_rhythm"><div class="half_rhythm">Early-onset developmental and epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity [<a class="bibr" href="#chd2-dis.REF.scheffer.2017.512" rid="chd2-dis.REF.scheffer.2017.512">Scheffer et al 2017</a>]), particularly those with:</div><ul><li class="half_rhythm"><div>Seizure onset between ages six months and four years</div></li><li class="half_rhythm"><div>Drop attacks and rapid onset of multiple seizure types associated with generalized spike-wave on EEG</div></li><li class="half_rhythm"><div>Atonic-myoclonic-absence seizures (See <a href="#chd2-dis.Clinical_Description">Clinical Description</a>.)</div></li><li class="half_rhythm"><div>Clinical photosensitivity</div></li></ul><div class="half_rhythm">Note: Photic stimulation during an EEG may be a helpful diagnostic modality (even though not all individuals with a <i>CHD2</i>-related neurodevelopmental disorder and clinical photosensitivity show an EEG response to photic stimulation). However, the possible increased risk for photic-induced seizures in individuals with this disorder should be taken into account when obtaining an EEG with photic stimulation.</div></li><li class="half_rhythm"><div class="half_rhythm">Intellectual disability and/or autism spectrum disorders, particularly when epilepsy is also present</div></li></ul></div><div id="chd2-dis.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of a <b><i>CHD2</i>-related neurodevelopmental disorder</b>
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<b>is established</b> in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in <i>CHD2</i> identified by molecular genetic testing (see <a href="/books/NBK333201/table/chd2-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobchd2disTmoleculargenetictestinguse">Table 1</a>).</p><p>Note: Per ACMG variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (multigene panel) or <b>genomic testing</b> (chromosomal microarray analysis [CMA] or comprehensive genomic sequencing).</p><p>Gene-targeted testing requires the clinician to determine which gene(s) are likely involved, whereas genomic testing may not. Because the phenotypes of many genetic epileptic encephalopathies overlap, most children with <i>CHD2</i>-related neurodevelopmental disorder with epilepsy are diagnosed by the following <a href="#chd2-dis.Recommended_Testing">recommended testing</a> (a multigene panel or CMA) or <a href="#chd2-dis.Testing_to_Consider">testing to be considered</a> (comprehensive genomic sequencing).</p><div id="chd2-dis.Recommended_Testing"><h4>Recommended Testing</h4><p><b>An epilepsy or intellectual disability multigene panel</b> that includes <i>CHD2</i> and other genes of interest (see <a href="#chd2-dis.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p><b>Chromosome microarray analysis (CMA)</b> uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>CHD2</i>) that cannot be detected by sequence analysis.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="chd2-dis.Testing_to_Consider"><h4>Testing to Consider</h4><p><b>Comprehensive genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used and yields results similar to an intellectual disability multigene panel with the additional advantage that exome sequencing includes genes recently identified as causing intellectual disability whereas some multigene panels may not.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><p><b>Resolution of variants of uncertain significance (VUS).</b> Many disorders that perturb regulators of epigenetic processes result in a very specific DNA methylation pattern that is common to all affected individuals with pathogenic variants in that gene [<a class="bibr" href="#chd2-dis.REF.arefeshghi.2020.356" rid="chd2-dis.REF.arefeshghi.2020.356">Aref-Eshghi et al 2020</a>]. Identification of an "episignature" characteristic of <i>CHD2</i>-related neurodevelopmental disorders can be used to resolve VUS in <i>CHD2</i>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2disTmoleculargenetictestinguse"><a href="/books/NBK333201/table/chd2-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobchd2disTmoleculargenetictestinguse"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.T.molecular_genetic_testing_use"><a href="/books/NBK333201/table/chd2-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object" rid-ob="figobchd2disTmoleculargenetictestinguse">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>CHD2</i>-Related Neurodevelopmental Disorders </p></div></div></div></div></div><div id="chd2-dis.Clinical_Characteristics"><h2 id="_chd2-dis_Clinical_Characteristics_">Clinical Characteristics</h2><div id="chd2-dis.Clinical_Description"><h3>Clinical Description</h3><p>To date 139 individuals with a <i>CHD2</i>-related neurodevelopmental disorder have been reported [<a class="bibr" href="#chd2-dis.REF.carvill.2013.825" rid="chd2-dis.REF.carvill.2013.825">Carvill et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.suls.2013.967" rid="chd2-dis.REF.suls.2013.967">Suls et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.oroak.2014.5595" rid="chd2-dis.REF.oroak.2014.5595">O'Roak et al 2014</a>, <a class="bibr" href="#chd2-dis.REF.deciphering_developmental_disorders_study_group.2015.223" rid="chd2-dis.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group 2015</a>, <a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>, <a class="bibr" href="#chd2-dis.REF.heyne.2018.1048" rid="chd2-dis.REF.heyne.2018.1048">Heyne et al 2018</a>, <a class="bibr" href="#chd2-dis.REF.ko.2018.48" rid="chd2-dis.REF.ko.2018.48">Ko et al 2018</a>, <a class="bibr" href="#chd2-dis.REF.truty.2019.397" rid="chd2-dis.REF.truty.2019.397">Truty et al 2019</a>, <a class="bibr" href="#chd2-dis.REF.chen.2020.647" rid="chd2-dis.REF.chen.2020.647">Chen et al 2020</a>].</p><p>A systematic single study of individuals with <i>CHD2</i>-related neurodevelopmental disorders has not yet been published. To date, epilepsy is a consistent feature across the phenotypic spectrum of <i>CHD2</i>-related neurodevelopmental disorders and most individuals reported have presented with developmental and epileptic encephalopathy. However, as genetic testing becomes more widely available and less targeted (i.e., more genes are included in multigene panels) the phenotypic spectrum is evolving.</p><p>The most common clinical features of these individuals are described below.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2disTselectfeaturesofchd2relate"><a href="/books/NBK333201/table/chd2-dis.T.select_features_of_chd2relate/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobchd2disTselectfeaturesofchd2relate"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.T.select_features_of_chd2relate"><a href="/books/NBK333201/table/chd2-dis.T.select_features_of_chd2relate/?report=objectonly" target="object" rid-ob="figobchd2disTselectfeaturesofchd2relate">Table 2. </a></h4><p class="float-caption no_bottom_margin">Select Features of <i>CHD2</i>-Related Neurodevelopmental Disorders </p></div></div><p><b>Seizures.</b> The age of onset ranges from six months to 12 years; median seizure onset is 30 months (2.5 years).</p><p>Seizure onset, which is explosive in many children, is characterized by multiple daily myoclonic and absence seizures.</p><p>Although <i>CHD2</i>-related epilepsy has been compared to Dravet syndrome in at least one study, febrile seizures, which are characteristic of Dravet syndrome, have only been reported in 11 individuals with <i>CHD2</i> variants [<a class="bibr" href="#chd2-dis.REF.carvill.2013.825" rid="chd2-dis.REF.carvill.2013.825">Carvill et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.suls.2013.967" rid="chd2-dis.REF.suls.2013.967">Suls et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>, <a class="bibr" href="#chd2-dis.REF.petersen.2018.1667" rid="chd2-dis.REF.petersen.2018.1667">Petersen et al 2018</a>, <a class="bibr" href="#chd2-dis.REF.chen.2020.647" rid="chd2-dis.REF.chen.2020.647">Chen et al 2020</a>].</p><p>A classic seizure type termed "atonic-myoclonic-absence seizure," a progressive seizure pattern comprising an abrupt head nod and atonia followed by a myoclonic absence phase and progression to a "ratchet-like" tonic abduction of the upper limbs, was observed in video footage of three children aged two to seven years. Seizures were brief (2-8 seconds) and awareness rapidly returned [<a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>]. Many of the components of this seizure pattern have been described in other affected individuals; thus, future video monitoring and video EEG monitoring will be important in determining if this seizure pattern is a hallmark of <i>CHD2</i>-related neurodevelopmental disorders.</p><p>Clinical photosensitivity (i.e., seizures triggered by photic stimulation) is a distinguishing feature reported in a total of 80% (20/25) of individuals where it was specifically queried. A small number of individuals could self-induce seizures, suggesting an unusually strong degree of photosensitivity. In contrast, a photoparoxysmal response (an epileptiform EEG response to intermittent photic stimulation) has only been recorded in two affected individuals [<a class="bibr" href="#chd2-dis.REF.lund.2014.18" rid="chd2-dis.REF.lund.2014.18">Lund et al 2014</a>, <a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>, <a class="bibr" href="#chd2-dis.REF.trivisano.2015.53" rid="chd2-dis.REF.trivisano.2015.53">Trivisano et al 2015</a>]. Of note, some individuals with a <i>CHD2</i> pathogenic variant have a diagnosis of eyelid myoclonia with absences, a particularly photosensitive epilepsy syndrome [<a class="bibr" href="#chd2-dis.REF.galizia.2015.1198" rid="chd2-dis.REF.galizia.2015.1198">Galizia et al 2015</a>].</p><p>Seizures are often refractory to currently available anti-seizure medications (ASMs). Only 13 of 33 affected individuals have been reported to be seizure free on ASM treatment for two to five years (see <a href="#chd2-dis.Management">Management</a>) [<a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>, <a class="bibr" href="#chd2-dis.REF.chen.2020.647" rid="chd2-dis.REF.chen.2020.647">Chen et al 2020</a>].</p><p><b>Psychomotor development</b> prior to seizures can be delayed (n=20) but is often not reported and this feature requires further evaluation. When specifically reported in the literature, intellectual disability ranges from mild (in 7/15 individuals) to severe (8/15 individuals).</p><p><b>Behavior and neuropsychiatric phenotypes.</b> Autism spectrum disorder or autistic features have been reported in 56% (39/70) of individuals. Challenging behaviors, most often aggression, have been described, with three requiring medical treatment with risperidone [<a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>]. Attention-deficit/hyperactivity disorder and psychosis have also been reported in a small number of individuals. There is also a single individual diagnosed with schizophrenia [<a class="bibr" href="#chd2-dis.REF.poisson.2020.10" rid="chd2-dis.REF.poisson.2020.10">Poisson et al 2020</a>]. It is currently unclear to what extent a specific behavior phenotype is part of the phenotypic spectrum and this requires further investigation for management.</p><p><b>Neuroimaging.</b> In some affected individuals MRI has shown atrophy that tends to be more posterior and can be progressive. In those with ataxia, cerebellar atrophy was more pronounced [<a class="bibr" href="#chd2-dis.REF.suls.2013.967" rid="chd2-dis.REF.suls.2013.967">Suls et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>].</p></div><div id="chd2-dis.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlation has been observed between the location/nature of the pathogenic variant and clinical outcome.</p></div><div id="chd2-dis.Penetrance"><h3>Penetrance</h3><p>Penetrance for <i>CHD2</i>-related neurodevelopmental disorders is unknown but assumed to be complete. There are a small number of instances where the <i>CHD2</i> variant is inherited from a presumably unaffected parent or a parent with a milder phenotype [<a class="bibr" href="#chd2-dis.REF.petersen.2018.1667" rid="chd2-dis.REF.petersen.2018.1667">Petersen et al 2018</a>, <a class="bibr" href="#chd2-dis.REF.chen.2020.647" rid="chd2-dis.REF.chen.2020.647">Chen et al 2020</a>]. In such instances it is important to evaluate the parent for somatic mosaicism.</p></div><div id="chd2-dis.Prevalence"><h3>Prevalence</h3><p>The prevalence of <i>CHD2-</i>related neurodevelopmental disorders is not known.</p><p>A <i>de novo</i>
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<i>CHD2</i> pathogenic variant was present in an estimated 1% of individuals included in cohorts with various developmental and epileptic encephalopathies [<a class="bibr" href="#chd2-dis.REF.allen.2013.217" rid="chd2-dis.REF.allen.2013.217">Allen et al 2013</a>, <a class="bibr" href="#chd2-dis.REF.carvill.2013.825" rid="chd2-dis.REF.carvill.2013.825">Carvill et al 2013</a>]. In another report of nearly 10,000 individuals referred for genetic testing using a comprehensive epilepsy panel, 0.25% of individuals has a <i>CHD2</i> pathogenic variant identified [<a class="bibr" href="#chd2-dis.REF.truty.2019.397" rid="chd2-dis.REF.truty.2019.397">Truty et al 2019</a>]. In individuals with a neurodevelopmental disorder that included epilepsy, <i>CHD2</i> was the fourth most highly implicated gene [<a class="bibr" href="#chd2-dis.REF.heyne.2018.1048" rid="chd2-dis.REF.heyne.2018.1048">Heyne et al 2018</a>].</p><p>In each of four studies of exome-based sequencing of hundreds to thousands of individuals with neurodevelopmental disorders including intellectual disability and autism spectrum disorders, one to three individuals with a <i>de novo</i>
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<i>CHD2</i> pathogenic variant were identified [<a class="bibr" href="#chd2-dis.REF.neale.2012.242" rid="chd2-dis.REF.neale.2012.242">Neale et al 2012</a>, <a class="bibr" href="#chd2-dis.REF.rauch.2012.1674" rid="chd2-dis.REF.rauch.2012.1674">Rauch et al 2012</a>, <a class="bibr" href="#chd2-dis.REF.oroak.2014.5595" rid="chd2-dis.REF.oroak.2014.5595">O'Roak et al 2014</a>, <a class="bibr" href="#chd2-dis.REF.deciphering_developmental_disorders_study_group.2015.223" rid="chd2-dis.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group 2015</a>].</p></div></div><div id="chd2-dis.Genetically_Related_Allelic_Dis"><h2 id="_chd2-dis_Genetically_Related_Allelic_Dis_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CHD2</i>.</p></div><div id="chd2-dis.Differential_Diagnosis"><h2 id="_chd2-dis_Differential_Diagnosis_">Differential Diagnosis</h2><p>Phenotypic features associated with <i>CHD2</i> pathogenic variants are not sufficient to diagnose <i>CHD2</i>-related neurodevelopmental disorders.</p><p><b>For children with a phenotype consistent with early-onset epileptic encephalopathy</b>, all genes known to be associated with epileptic encephalopathy (~90 have been identified; see OMIM <a href="https://omim.org/phenotypicSeries/PS308350" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Phenotypic Series</a>) should be included in the differential diagnosis.</p><p><b>For children with intellectual disability and epilepsy</b>, all genes associated with juvenile myoclonic epilepsy (see OMIM <a href="https://omim.org/phenotypicSeries/PS254770" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Phenotypic Series</a>), idiopathic generalized epilepsy (see OMIM <a href="https://omim.org/phenotypicSeries/PS600669" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Phenotypic Series</a>), and generalized epilepsy with febrile seizures plus (see OMIM <a href="https://omim.org/phenotypicSeries/PS604233" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Phenotypic Series</a>) should be included in the differential diagnosis.</p></div><div id="chd2-dis.Management"><h2 id="_chd2-dis_Management_">Management</h2><div id="chd2-dis.Evaluations_Following_Initial_D"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a <i>CHD2</i>-related neurodevelopmental disorder, the evaluations summarized in <a href="/books/NBK333201/table/chd2-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobchd2disTrecommendedevaluationsfollo">Table 3</a> (if not performed as part of the evaluation that led to diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2disTrecommendedevaluationsfollo"><a href="/books/NBK333201/table/chd2-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobchd2disTrecommendedevaluationsfollo"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.T.recommended_evaluations_follo"><a href="/books/NBK333201/table/chd2-dis.T.recommended_evaluations_follo/?report=objectonly" target="object" rid-ob="figobchd2disTrecommendedevaluationsfollo">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders </p></div></div></div><div id="chd2-dis.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2disTtreatmentofmanifestationsi"><a href="/books/NBK333201/table/chd2-dis.T.treatment_of_manifestations_i/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobchd2disTtreatmentofmanifestationsi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.T.treatment_of_manifestations_i"><a href="/books/NBK333201/table/chd2-dis.T.treatment_of_manifestations_i/?report=objectonly" target="object" rid-ob="figobchd2disTtreatmentofmanifestationsi">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders </p></div></div><div id="chd2-dis.Developmental_Delay__Intellectu"><h4>Developmental Delay / Intellectual Disability Management Issues</h4><p>The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.</p><p><b>Ages 0-3 years.</b> Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.</p><p><b>Ages 3-5 years.</b> In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.</p><p><b>All ages.</b> Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:</p><ul><li class="half_rhythm"><div>IEP services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>Special education law requires that children participating in an IPE be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.</div></li><li class="half_rhythm"><div>PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.</div></li><li class="half_rhythm"><div>As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li><li class="half_rhythm"><div>Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.</div></li><li class="half_rhythm"><div>Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.</div></li></ul></div><div id="chd2-dis.Motor_Dysfunction"><h4>Motor Dysfunction</h4><p><b>Gross motor dysfunction.</b> Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications. Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).</p><p><b>Fine motor dysfunction.</b> Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.</p><p><b>Oral motor dysfunction</b> should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.</p><p><b>Communication issues.</b> Consider evaluation for alternative means of communication (e.g., <a href="https://www.asha.org/NJC/AAC/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">augmentative and alternative communication</a> [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.</p></div><div id="chd2-dis.SocialBehavioral_Concerns"><h4>Social/Behavioral Concerns</h4><p>Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.</p><p>Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.</p><p>Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.</p></div></div><div id="chd2-dis.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2disTrecommendedsurveillancefor"><a href="/books/NBK333201/table/chd2-dis.T.recommended_surveillance_for/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobchd2disTrecommendedsurveillancefor"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.T.recommended_surveillance_for"><a href="/books/NBK333201/table/chd2-dis.T.recommended_surveillance_for/?report=objectonly" target="object" rid-ob="figobchd2disTrecommendedsurveillancefor">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders </p></div></div></div><div id="chd2-dis.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Because clinical photosensitivity may result in injuries due to the consequences of induced seizures, the following are recommended:</p><ul><li class="half_rhythm"><div>Avoid flickering lights that may provoke seizures.</div></li><li class="half_rhythm"><div>Advise affected individuals and families that exposure to intensely flickering lights may provoke seizures including eyelid myoclonias, absence seizures, and generalized tonic-clonic seizures. Of note, most televisions do not transmit in the frequency range that is particularly provocative.</div></li></ul></div><div id="chd2-dis.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#chd2-dis.Related_Genetic_Counseling_Issu">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="chd2-dis.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="chd2-dis.Genetic_Counseling"><h2 id="_chd2-dis_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="chd2-dis.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>CHD2</i>-related neurodevelopmental disorders are autosomal dominant disorders typically caused by a <i>de novo</i> pathogenic variant.</p></div><div id="chd2-dis.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>Almost all individuals diagnosed with a <i>CHD2</i>-related neurodevelopmental disorder have the disorder as the result of a <i>de novo</i> pathogenic variant.</div></li><li class="half_rhythm"><div>In rare families, individuals diagnosed with a <i>CHD2</i>-related neurodevelopmental disorder have the disorder as the result of a <i>CHD2</i> pathogenic variant inherited from a parent. For example:</div><ul><li class="half_rhythm"><div>A child with a severe presentation of <i>CHD2</i>-related neurodevelopmental disorder inherited a <i>CHD2</i> pathogenic variant from her heterozygous, less severely affected mother [<a class="bibr" href="#chd2-dis.REF.petersen.2018.1667" rid="chd2-dis.REF.petersen.2018.1667">Petersen et al 2018</a>]. Her mother had seizures as a child (well controlled with anti-seizure medications) and neuropsychiatric features (including bipolar disorder, ADHD, language delays, and dyslexia) but no learning difficulties throughout childhood [<a class="bibr" href="#chd2-dis.REF.petersen.2018.1667" rid="chd2-dis.REF.petersen.2018.1667">Petersen et al 2018</a>].</div></li><li class="half_rhythm"><div>A child with epilepsy and myoclonic seizures inherited a splice variant from his apparently unaffected heterozygous father [<a class="bibr" href="#chd2-dis.REF.chen.2020.647" rid="chd2-dis.REF.chen.2020.647">Chen et al 2020</a>].</div></li></ul></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The proband has a <i>de novo</i> pathogenic variant. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bibr" href="#chd2-dis.REF.richards.2015.405" rid="chd2-dis.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism. Presumed parental germline mosaicism was reported in a family with unaffected parents and sib recurrence [<a class="bibr" href="#chd2-dis.REF.lebrun.2017.669" rid="chd2-dis.REF.lebrun.2017.669">Lebrun et al 2017</a>]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism.</div></li></ul></li><li class="half_rhythm"><div>The family history of an individual diagnosed with a <i>CHD2</i>-related neurodevelopmental disorder may appear to be negative because of failure to recognize the disorder in family members. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs of the proband depends on the genetic status of the proband's parents.</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.</div></li><li class="half_rhythm"><div>If the proband has a known <i>CHD2</i> pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism [<a class="bibr" href="#chd2-dis.REF.lebrun.2017.669" rid="chd2-dis.REF.lebrun.2017.669">Lebrun et al 2017</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>CHD2</i> pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for a <i>CHD2</i>-related neurodevelopmental disorder because of the possibility of parental germline mosaicism [<a class="bibr" href="#chd2-dis.REF.lebrun.2017.669" rid="chd2-dis.REF.lebrun.2017.669">Lebrun et al 2017</a>, <a class="bibr" href="#chd2-dis.REF.myers.2018.1646" rid="chd2-dis.REF.myers.2018.1646">Myers et al 2018</a>].</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with a <i>CHD2</i>-related neurodevelopmental disorder has a 50% chance of inheriting the <i>CHD2</i> pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent has the <i>CHD2</i> pathogenic variant, the parent's family members may be at risk.</p></div><div id="chd2-dis.Related_Genetic_Counseling_Issu"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk of having a child with a <i>CHD2</i>-related neurodevelopmental disorder.</div></li></ul></div><div id="chd2-dis.Prenatal_Testing_and_Preimplant"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>CHD2</i> pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for a <i>CHD2</i>-related neurodevelopmental disorder are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="chd2-dis.Resources"><h2 id="_chd2-dis_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>Coalition to Cure CHD2</b>
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</div><div>
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<a href="https://www.curechd2.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.curechd2.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>American Epilepsy Society</b>
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</div><div>
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<a href="https://www.aesnet.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">aesnet.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Autism Society</b>
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</div><div><b>Phone:</b> 800-328-8476</div><div><b>Email:</b> info@autism-society.org</div><div>
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<a href="https://autismsociety.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">autismsociety.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Canadian Epilepsy Alliance</b>
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</div><div>Canada</div><div><b>Phone:</b> 1-866-EPILEPSY (1-866-374-5377)</div><div>
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<a href="https://www.canadianepilepsyalliance.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">canadianepilepsyalliance.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Citizens United for Research in Epilepsy (CURE)</b>
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</div><div>
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<a href="http://www.cureepilepsy.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.cureepilepsy.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Epilepsy Foundation</b>
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</div><div><b>Phone:</b> 800-332-1000; 866-748-8008</div><div>
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<a href="https://www.epilepsy.com/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">epilepsy.com</a>
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</div></li><li class="half_rhythm"><div>
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<b>Simons Searchlight Registry</b>
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</div><div>
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<i>Simons Searchlight aims to further the understanding of rare genetic neurodevelopmental disorders.</i>
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</div><div><b>Phone:</b> 855-329-5638</div><div><b>Fax:</b> 570-214-7327</div><div><b>Email:</b> coordinator@simonssearchlight.org</div><div>
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<a href="https://www.simonssearchlight.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">simonssearchlight.org</a>
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</div></li></ul>
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</div><div id="chd2-dis.Molecular_Genetics"><h2 id="_chd2-dis_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2dismolgenTA"><a href="/books/NBK333201/table/chd2-dis.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobchd2dismolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.molgen.TA"><a href="/books/NBK333201/table/chd2-dis.molgen.TA/?report=objectonly" target="object" rid-ob="figobchd2dismolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">CHD2-Related Neurodevelopmental Disorders: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figchd2dismolgenTB"><a href="/books/NBK333201/table/chd2-dis.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobchd2dismolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="chd2-dis.molgen.TB"><a href="/books/NBK333201/table/chd2-dis.molgen.TB/?report=objectonly" target="object" rid-ob="figobchd2dismolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for CHD2-Related Neurodevelopmental Disorders (View All in OMIM) </p></div></div><div id="chd2-dis.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>CHD2</i> encodes the chromodomain DNA helicase binding protein 2. CHD2 and additional members of this family of proteins are responsible for remodeling chromatin, which controls the three-dimensional architecture of the genome and gene expression. The protein consists of two chromodomains and a putative DNA binding domain; these domains are known or hypothesized to bind DNA [<a class="bibr" href="#chd2-dis.REF.marfella.2007.30" rid="chd2-dis.REF.marfella.2007.30">Marfella & Imbalzano 2007</a>, <a class="bibr" href="#chd2-dis.REF.liu.2015.25" rid="chd2-dis.REF.liu.2015.25">Liu et al 2015</a>]. The ATP-helicase and DEDX-helicase domain are known in other family members to remodel chromatin using the energy of ATP hydrolysis [<a class="bibr" href="#chd2-dis.REF.marfella.2007.30" rid="chd2-dis.REF.marfella.2007.30">Marfella & Imbalzano 2007</a>, <a class="bibr" href="#chd2-dis.REF.bouazoune.2012.19238" rid="chd2-dis.REF.bouazoune.2012.19238">Bouazoune & Kingston 2012</a>].</p><p>The overwhelming majority of <i>CHD2</i> pathogenic variants lead to either truncation of the protein or loss of gene expression by whole-gene deletion. The pathogenic missense variants cluster in the functional domains and likely impair the ability of CHD2 to either bind to DNA targets and/or remodel chromatin. Collectively this suggests that <i>CHD2-</i>related neurodevelopmental disorders result from haploinsufficiency of CHD2.</p><p>To date the majority of individuals with a <i>CHD2</i> pathogenic variant have a brain-restricted phenotype, suggesting a unique role for CHD2 in the human brain. The function of CHD2 in the human brain is not known. Complete CHD2 loss in a human stem cell model resulted in defects in the development of inhibitory interneurons and altered expression of genes important in neurotransmission [<a class="bibr" href="#chd2-dis.REF.meganathan.2017.e11180" rid="chd2-dis.REF.meganathan.2017.e11180">Meganathan et al 2017</a>]. A heterozygous Chd2 loss mouse showed deficits in neuronal development including reduced number of both excitatory and inhibitory neurons and severe impairments in long-term memory. These animals did not exhibit seizures [<a class="bibr" href="#chd2-dis.REF.kim.2018.1180" rid="chd2-dis.REF.kim.2018.1180">Kim et al 2018</a>].</p><p><b>Mechanism of disease causation.</b> The majority of pathogenic variants lead to truncation of <i>CHD2</i>. The few reported <i>de novo</i> missense pathogenic variants occur in the highly conserved DNA-binding or helicase domains and likely hinder the ability of CHD2 to remodel chromatin. <i>CHD2</i> pathogenic variants are likely all loss of function, resulting in <i>CHD2</i>-related neurodevelopmental disorders due to haploinsufficiency of CHD2.</p></div></div><div id="chd2-dis.Chapter_Notes"><h2 id="_chd2-dis_Chapter_Notes_">Chapter Notes</h2><div id="chd2-dis.Author_Notes"><h3>Author Notes</h3><p>The Epilepsiome: A knowledge base for genes related to human epilepsies:<br /><a href="http://epilepsygenetics.net/2015/10/26/chd2-this-is-what-you-need-to-know-in-2015/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHD2 – this is what you need to know in 2015</a></p><p><a href="https://www.stjude.org/research/labs/mefford-lab.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><b>Mefford Laboratory</b></a><br />St Jude Children’s Research Hospital<br />Center for Pediatric Neurological Disease Research <br />Department of Cell & Molecular Biology<br />262 Danny Thomas Place, Mail Stop 340<br />Memphis, TN 38105-3678</p><p><a href="https://sites.northwestern.edu/carvilllab/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><b>Carvill Laboratory</b></a><br />Northwestern University<br />303 E Chicago, Ward 9-183<br />Chicago, IL 60611<br />gemma.carvill@northwestern.edu<br />312-503-6187</p></div><div id="chd2-dis.Author_History"><h3>Author History</h3><p>Gemma Carvill, PhD (2015-present)<br />Ingo Helbig, MD; Children's Hospital of Philadelphia (2015-2021)<br />Heather Mefford, MD, PhD (2015-present)</p></div><div id="chd2-dis.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>21 January 2021 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>10 December 2015 (bp) Review posted live</div></li><li class="half_rhythm"><div>14 May 2015 (hm/gc) Original submission</div></li></ul></div></div><div id="chd2-dis.References"><h2 id="_chd2-dis_References_">References</h2><div id="chd2-dis.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.allen.2013.217">Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, McGuire SM, Motika PV, Novotny EJ, Paolicchi JM, Parent JM, Park K, Shellhaas RA, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. De novo mutations in epileptic encephalopathies. <span><span class="ref-journal">Nature. </span>2013;<span class="ref-vol">501</span>:217–21.</span> [<a href="/pmc/articles/PMC3773011/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3773011</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23934111" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23934111</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.arefeshghi.2020.356">Aref-Eshghi E, Kerkhof J, Pedro VP, Groupe DI. France, Barat-Houari M, Ruiz-Pallares N, Andrau JC, Lacombe D, Van-Gils J, Fergelot P, Dubourg C, Cormier-Daire V, Rondeau S, Lecoquierre F, Saugier-Veber P, Nicolas G, Lesca G, Chatron N, Sanlaville D, Vitobello A, Faivre L, Thauvin-Robinet C, Laumonnier F, Raynaud M, Alders M, Mannens M, Henneman P, Hennekam RC, Velasco G, Francastel C, Ulveling D, Ciolfi A, Pizzi S, Tartaglia M, Heide S, Héron D, Mignot C, Keren B, Whalen S, Afenjar A, Bienvenu T, Campeau PM, Rousseau J, Levy MA, Brick L, Kozenko M, Balci TB, Siu VM, Stuart A, Kadour M, Masters J, Takano K, Kleefstra T, de Leeuw N, Field M, Shaw M, Gecz J, Ainsworth PJ, Lin H, Rodenhiser DI, Friez MJ, Tedder M, Lee JA, DuPont BR, Stevenson RE, Skinner SA, Schwartz CE, Genevieve D, Sadikovic B. Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 Mendelian neurodevelopmental disorders. <span><span class="ref-journal">Am J Hum Genet. </span>2020;<span class="ref-vol">106</span>:356–70.</span> [<a href="/pmc/articles/PMC7058829/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7058829</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32109418" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32109418</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.bouazoune.2012.19238">Bouazoune K, Kingston RE. Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2012;<span class="ref-vol">109</span>:19238–43.</span> [<a href="/pmc/articles/PMC3511097/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3511097</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23134727" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23134727</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.capelli.2012.132">Capelli LP, Krepischi AC, Gurgel-Giannetti J, Mendes MF, Rodrigues T, Varela MC, Koiffmann CP, Rosenberg C. Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency. <span><span class="ref-journal">Eur J Med Genet. </span>2012;<span class="ref-vol">55</span>:132–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22178256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22178256</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.carvill.2013.825">Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Moller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. <span><span class="ref-journal">Nat Genet. </span>2013;<span class="ref-vol">45</span>:825–30.</span> [<a href="/pmc/articles/PMC3704157/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3704157</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23708187" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23708187</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.chen.2020.647">Chen J, Zhang J, Liu A, Zhang L, Li H, Zeng Q, Yang Z, Yang X, Wu X, Zhang Y. CHD2-related epilepsy: novel mutations and new phenotypes. <span><span class="ref-journal">Dev Med Child Neurol. </span>2020;<span class="ref-vol">62</span>:647–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/31677157" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31677157</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.ch_nier.2014.9">Chénier S, Yoon G, Argiropoulos B, Lauzon J, Laframboise R, Ahn JW, Ogilvie CM, Lionel AC, Marshall CR, Vaags AK, Hashemi B, Boisvert K, Mathonnet G, Tihy F, So J, Scherer SW, Lemyre E, Stavropoulos DJ. CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems. <span><span class="ref-journal">J Neurodev Disord. </span>2014;<span class="ref-vol">6</span>:9.</span> [<a href="/pmc/articles/PMC4022362/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4022362</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24834135" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24834135</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.courage.2014.520">Courage C, Houge G, Gallati S, Schjelderup J, Rieubland C. 15q26.1 microdeletion encompassing only CHD2 and RGMA in two adults with moderate intellectual disability, epilepsy and truncal obesity. <span><span class="ref-journal">Eur J Med Genet. </span>2014;<span class="ref-vol">57</span>:520–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24932903" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24932903</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.dhamija.2011.60">Dhamija R, Breningstall G, Wong-Kisiel L, Dolan M, Hirsch B, Wirrell E. Microdeletion of chromosome 15q26.1 in a child with intractable generalized epilepsy. <span><span class="ref-journal">Pediatr Neurol. </span>2011;<span class="ref-vol">45</span>:60–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21723464" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21723464</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.deciphering_developmental_disorders_study_group.2015.223">Deciphering Developmental Disorders Study Group. Large-scale discovery of novel genetic causes of developmental disorders. <span><span class="ref-journal">Nature. </span>2015;<span class="ref-vol">519</span>:223–8.</span> [<a href="/pmc/articles/PMC5955210/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5955210</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25533962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25533962</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.galizia.2015.1198">Galizia EC, Myers CT, Leu C, de Kovel CGF, Afrikanova T, Cordero-Maldonado ML, Martins TG, Jacmin M, Drury S, Chinthapalli VK, Muhle H, Pendziwiat M, Sander T, Ruppert A-K, Moller RS, Thiele H, Krause R, Schubert J, Lehesjoki A-E, Nurnberg P, Lerche H, Palotie A, Coppola A, Striano S, Del Gaudio L, Boustred C, Schneider AL, Lench N, Jocic-Jakubi B, Covanis A, Capovilla G, Veggotti P, Piccioli M, Parisi P, Cantonetti L, Sadleir LG, Mullen SA, Berkovic SF, Stephani U, Helbig I, Crawford AD, Esguerra CV, Kasteleijn-Nolst Trenite DGA, Koeleman BPC, Mefford HC, Scheffer IE, Sisodiya SM. CHD2 variants are a risk factor for photosensitivity in epilepsy. <span><span class="ref-journal">Brain. </span>2015;<span class="ref-vol">138</span>:1198–207.</span> [<a href="/pmc/articles/PMC4407192/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4407192</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25783594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25783594</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.heyne.2018.1048">Heyne HO, Singh T, Stamberger H, Abou Jamra R, Caglayan H, Craiu D, De Jonghe P, Guerrini R, Helbig KL, Koeleman BPC, Kosmicki JA, Linnankivi T, May P, Muhle H, Møller RS, Neubauer BA, Palotie A, Pendziwiat M, Striano P, Tang S, Wu S. EuroEPINOMICS RES Consortium, Poduri A, Weber YG, Weckhuysen S, Sisodiya SM, Daly MJ, Helbig I, Lal D, Lemke JR. De novo variants in neurodevelopmental disorders with epilepsy. <span><span class="ref-journal">Nat Genet. </span>2018;<span class="ref-vol">50</span>:1048–53.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29942082" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29942082</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.kim.2018.1180">Kim YJ, Khoshkhoo S, Frankowski JC, Zhu B, Abbasi S, Lee S, Wu YE, Hunt RF. Chd2 is necessary for neural circuit development and long-term memory neuron. <span><span class="ref-journal">Neuron. </span>2018;<span class="ref-vol">100</span>:1180–93.e6.</span> [<a href="/pmc/articles/PMC6479120/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6479120</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30344048" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30344048</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.ko.2018.48">Ko A, Youn SE, Kim SH, Lee JS, Kim S, Choi JR, Kim HD, Lee ST, Kang HC. Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy. <span><span class="ref-journal">Epilepsy Res. </span>2018;<span class="ref-vol">141</span>:48–55.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29455050" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29455050</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.lebrun.2017.669">Lebrun N, Parent P, Gendras J, Billuart P, Poirier K, Bienvenu T. Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant. <span><span class="ref-journal">Clin Genet. </span>2017;<span class="ref-vol">92</span>:669–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28960266" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28960266</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.liu.2015.25">Liu JC, Ferreira CG, Yusufzai T. Human CHD2 is a chromatin assembly ATPase regulated by its chromo- and DNA-binding domains. <span><span class="ref-journal">J Biol Chem. </span>2015;<span class="ref-vol">290</span>:25–34.</span> [<a href="/pmc/articles/PMC4281729/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4281729</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25384982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25384982</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.lund.2014.18">Lund C, Brodtkorb E, Oye AM, Rosby O, Selmer KK. CHD2 mutations in Lennox-Gastaut syndrome. <span><span class="ref-journal">Epilepsy Behav. </span>2014;<span class="ref-vol">33</span>:18–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24614520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24614520</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.marfella.2007.30">Marfella CG, Imbalzano AN. The Chd family of chromatin remodelers. <span><span class="ref-journal">Mutat Res. </span>2007;<span class="ref-vol">618</span>:30–40.</span> [<a href="/pmc/articles/PMC1899158/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1899158</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17350655" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17350655</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.meganathan.2017.e11180">Meganathan K, Lewis EMA, Gontarz P, Liu S, Stanley EG, Elefanty AG, Huettner JE, Zhang B, Kroll KL. Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2017;<span class="ref-vol">114</span>:E11180–9.</span> [<a href="/pmc/articles/PMC5748186/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5748186</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29229852" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29229852</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.myers.2018.1646">Myers CT, Hollingsworth G, Muir AM, Schneider AL, Thuesmunn Z, Knupp A, King C, Lacroix A, Mehaffey MG, Berkovic SF, Carvill GL, Sadleir LG, Scheffer IE, Mefford HC. Parental mosaicism in "de novo" epileptic encephalopathies. <span><span class="ref-journal">N Engl J Med. </span>2018;<span class="ref-vol">378</span>:1646–8.</span> [<a href="/pmc/articles/PMC5966016/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5966016</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29694806" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29694806</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.neale.2012.242">Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE, Sabo A, Lin CF, Stevens C, Wang LS, Makarov V, Polak P, Yoon S, Maguire J, Crawford EL, Campbell NG, Geller ET, Valladares O, Schafer C, Liu H, Zhao T, Cai G, Lihm J, Dannenfelser R, Jabado O, Peralta Z, Nagaswamy U, Muzny D, Reid JG, Newsham I, Wu Y, Lewis L, Han Y, Voight BF, Lim E, Rossin E, Kirby A, Flannick J, Fromer M, Shakir K, Fennell T, Garimella K, Banks E, Poplin R, Gabriel S, DePristo M, Wimbish JR, Boone BE, Levy SE, Betancur C, Sunyaev S, Boerwinkle E, Buxbaum JD, Cook EH Jr, Devlin B, Gibbs RA, Roeder K, Schellenberg GD, Sutcliffe JS, Daly MJ. Patterns and rates of exonic de novo mutations in autism spectrum disorders. <span><span class="ref-journal">Nature. </span>2012;<span class="ref-vol">485</span>:242–5.</span> [<a href="/pmc/articles/PMC3613847/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3613847</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22495311" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22495311</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.oroak.2014.5595">O'Roak BJ, Stessman HA, Boyle EA, Witherspoon KT, Martin B, Lee C, Vives L, Baker C, Hiatt JB, Nickerson DA, Bernier R, Shendure J, Eichler EE. Recurrent de novo mutations implicate novel genes underlying simplex autism risk. <span><span class="ref-journal">Nat Commun. </span>2014;<span class="ref-vol">5</span>:5595.</span> [<a href="/pmc/articles/PMC4249945/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4249945</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25418537" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25418537</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.petersen.2018.1667">Petersen AK, Streff H, Tokita M, Bostwick BL. The first reported case of an inherited pathogenic CHD2 variant in a clinically affected mother and daughter. <span><span class="ref-journal">Am J Med Genet A. </span>2018;<span class="ref-vol">176</span>:1667–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29740950" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29740950</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.pinto.2014.677">Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, Scherer SW. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. <span><span class="ref-journal">Am J Hum Genet. </span>2014;<span class="ref-vol">94</span>:677–94.</span> [<a href="/pmc/articles/PMC4067558/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4067558</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24768552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24768552</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.poisson.2020.10">Poisson A, Chatron N, Labalme A, Fourneret P, Ville D, Mathieu ML, Sanlaville D, Demily C, Lesca G. Chromatin remodeling dysfunction extends the etiological spectrum of schizophrenia: a case report. <span><span class="ref-journal">BMC Med Genet. </span>2020;<span class="ref-vol">21</span>:10.</span> [<a href="/pmc/articles/PMC6950831/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6950831</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31914951" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31914951</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.rauch.2012.1674">Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Ropke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, Wohlleber E, Zweier C, Ekici AB, Zink AM, Rump A, Meisinger C, Grallert H, Sticht H, Schenck A, Engels H, Rappold G, Schrock E, Wieacker P, Riess O, Meitinger T, Reis A, Strom TM. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. <span><span class="ref-journal">Lancet. </span>2012;<span class="ref-vol">380</span>:1674–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23020937" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23020937</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.scheffer.2017.512">Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. <span><span class="ref-journal">Epilepsia. </span>2017;<span class="ref-vol">58</span>:512–21.</span> [<a href="/pmc/articles/PMC5386840/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5386840</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28276062" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28276062</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.suls.2013.967">Suls A, Jaehn JA, Kecskes A, Weber Y, Weckhuysen S, Craiu DC, Siekierska A, Djemie T, Afrikanova T, Gormley P, von Spiczak S, Kluger G, Iliescu CM, Talvik T, Talvik I, Meral C, Caglayan HS, Giraldez BG, Serratosa J, Lemke JR, Hoffman-Zacharska D, Szczepanik E, Barisic N, Komarek V, Hjalgrim H, Moller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, Kuhlenbaumer G, Crawford AD, Lehesjoki AE, de Witte PA, Palotie A, Lerche H, Esguerra CV, De Jonghe P, Helbig I. De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome. <span><span class="ref-journal">Am J Hum Genet. </span>2013;<span class="ref-vol">93</span>:967–75.</span> [<a href="/pmc/articles/PMC3824114/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3824114</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24207121" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24207121</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.thomas.2015.951">Thomas RH, Zhang LM, Carvill GL, Archer JS, Heavin SB, Mandelstam SA, Craiu D, Berkovic SF, Gill DS, Mefford HC, Scheffer IE. CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures. <span><span class="ref-journal">Neurology. </span>2015;<span class="ref-vol">84</span>:951–8.</span> [<a href="/pmc/articles/PMC4351660/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4351660</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25672921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25672921</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.trivisano.2015.53">Trivisano M, Striano P, Sartorelli J, Giordano L, Traverso M, Accorsi P, Cappelletti S, Claps DJ, Vigevano F, Zara F, Specchio N. CHD2 mutations are a rare cause of generalized epilepsy with myoclonic-atonic seizures. <span><span class="ref-journal">Epilepsy Behav. </span>2015;<span class="ref-vol">51</span>:53–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26262932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26262932</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="chd2-dis.REF.truty.2019.397">Truty R, Patil N, Sankar R, Sullivan J, Millichap J, Carvill G, Entezam A, Esplin ED, Fuller A, Hogue M, Johnson B, Khouzam A, Kobayashi Y, Lewis R, Nykamp K, Riethmaier D, Westbrook J, Zeman M, Nussbaum RL, Aradhya S. Possible precision medicine implications from genetic testing using combined detection of sequence and intragenic copy number variants in a large cohort with childhood epilepsy. <span><span class="ref-journal">Epilepsia Open. </span>2019;<span class="ref-vol">4</span>:397–408.</span> [<a href="/pmc/articles/PMC6698688/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6698688</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31440721" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31440721</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK333201_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Gemma L Carvill</span>, PhD<div class="affiliation small">Department of Neurology<br />Northwestern University<br />Evanston, Illinois<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.nretsewhtron@llivrac.ammeg" class="oemail">ude.nretsewhtron@llivrac.ammeg</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Heather C Mefford</span>, MD, PhD<div class="affiliation small">Professor, Center for Pediatric Neurological Disease Research<br />Department of Cellular and Molecular Biology<br />St Jude Children's Research Hospital<br />Memphis, Tennessee<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="gro.edujts@droffem.rehtaeh" class="oemail">gro.edujts@droffem.rehtaeh</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">December 10, 2015</span>; Last Update: <span itemprop="dateModified">January 21, 2021</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. 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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Carvill GL, Mefford HC. CHD2-Related Neurodevelopmental Disorders. 2015 Dec 10 [Updated 2021 Jan 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/chchd10-dis/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/chd4-ndd/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobchd2disTmoleculargenetictestinguse"><div id="chd2-dis.T.molecular_genetic_testing_use" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>CHD2</i>-Related Neurodevelopmental Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.T.molecular_genetic_testing_use/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.T.molecular_genetic_testing_use_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a <i>CHD2</i> Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CHD2</i>
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</td><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">129/139 (93%) <sup>4</sup></td></tr><tr><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">CMA <sup>5</sup></td><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10/139 (7%) <sup>6</sup></td></tr><tr><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>7</sup></td><td headers="hd_h_chd2-dis.T.molecular_genetic_testing_use_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="chd2-dis.TF.1.1"><p class="no_margin">See <a href="/books/NBK333201/?report=reader#chd2-dis.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="chd2-dis.TF.1.2"><p class="no_margin">See <a href="#chd2-dis.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="chd2-dis.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="chd2-dis.TF.1.4"><p class="no_margin">Data derived from author review of variants reported in the literature, large-scale cohort exome studies, and data from genetic testing companies [Author, personal communication]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="chd2-dis.TF.1.5"><p class="no_margin">Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including <i>CHD2</i>) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the 15q26 region. CMA designs in current clinical use target the 15q26 region.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="chd2-dis.TF.1.6"><p class="no_margin">Individuals with features of <i>CHD2-</i>related disorders who have deletions encompassing <i>CHD2</i> (with or without deletion of <i>RGMA)</i> have been reported [<a class="bibr" href="#chd2-dis.REF.dhamija.2011.60" rid="chd2-dis.REF.dhamija.2011.60">Dhamija et al 2011</a>, <a class="bibr" href="#chd2-dis.REF.capelli.2012.132" rid="chd2-dis.REF.capelli.2012.132">Capelli et al 2012</a>, <a class="bibr" href="#chd2-dis.REF.ch_nier.2014.9" rid="chd2-dis.REF.ch_nier.2014.9">Chénier et al 2014</a>, <a class="bibr" href="#chd2-dis.REF.courage.2014.520" rid="chd2-dis.REF.courage.2014.520">Courage et al 2014</a>, <a class="bibr" href="#chd2-dis.REF.pinto.2014.677" rid="chd2-dis.REF.pinto.2014.677">Pinto et al 2014</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="chd2-dis.TF.1.7"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="chd2-dis.TF.1.8"><p class="no_margin">No intragenic <i>CHD2</i> multiexon deletions or duplications have been reported.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchd2disTselectfeaturesofchd2relate"><div id="chd2-dis.T.select_features_of_chd2relate" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Select Features of <i>CHD2</i>-Related Neurodevelopmental Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.T.select_features_of_chd2relate/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.T.select_features_of_chd2relate_lrgtbl__"><table><thead><tr><th id="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th></tr></thead><tbody><tr><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Seizures</td><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">96% (108/113)</td></tr><tr><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental delay / Intellectual disability</td><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">95% (81/85)</td></tr><tr><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Autism spectrum disorder</td><td headers="hd_h_chd2-dis.T.select_features_of_chd2relate_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">56% (39/70)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchd2disTrecommendedevaluationsfollo"><div id="chd2-dis.T.recommended_evaluations_follo" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.T.recommended_evaluations_follo/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.T.recommended_evaluations_follo_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neurologic eval</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">EEG</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To assess degree of epileptic encephalopathy</div></li><li class="half_rhythm"><div>May lead to more focused use of ASMs</div></li></ul>
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</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">MRI</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To differentiate genetic epilepsy from lesional epilepsy</div></li><li class="half_rhythm"><div>May lead to intensified conservative treatment rather than presurgical work up</div></li></ul>
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</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Developmental assessment</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>To incl motor, adaptive, cognitive, & speech/language eval</div></li><li class="half_rhythm"><div>Eval for early intervention / special education</div></li></ul>
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</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
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<br />
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<b>Behavioral</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Neuropsychiatric eval</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">For persons age >12 mos: screening for behavior concerns incl sleep disturbances, ADHD, anxiety, aggression, &/or traits suggestive of ASD</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
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<br />
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<b>counseling</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & their families re nature, MOI, & implications of <i>CHD2-</i>related neurodevelopmental disorders to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family support</b>
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<br />
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<b>& resources</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
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<ul><li class="half_rhythm"><div>Community or <a href="#chd2-dis.Resources">online resources</a> such as <a href="https://www.p2pusa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Parent to Parent</a>;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
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</td><td headers="hd_h_chd2-dis.T.recommended_evaluations_follo_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; ASMs = anti-seizure medications; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="chd2-dis.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, or certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchd2disTtreatmentofmanifestationsi"><div id="chd2-dis.T.treatment_of_manifestations_i" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.T.treatment_of_manifestations_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.T.treatment_of_manifestations_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Epilepsy</b>
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</td><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standardized treatment w/ASM by experienced neurologist</td><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Many ASMs may be effective; none have been demonstrated effective specifically for this disorder. <sup>1, 2</sup></div></li><li class="half_rhythm"><div>Education of parents/caregivers <sup>3</sup></div></li></ul>
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</td></tr><tr><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Developmental delay / Intellectual disability</b>
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</td><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#chd2-dis.Developmental_Delay__Intellectu">Developmental Delay / Intellectual Disability Management Issues</a>.</td><td headers="hd_h_chd2-dis.T.treatment_of_manifestations_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ASMs = anti-seizure medications</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="chd2-dis.TF.4.1"><p class="no_margin">Most individuals remain refractory to treatment and require multiple ASMs.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="chd2-dis.TF.4.2"><p class="no_margin">Although a ketogenic diet may be a treatment option, it was not effective in three affected individuals [<a class="bibr" href="#chd2-dis.REF.thomas.2015.951" rid="chd2-dis.REF.thomas.2015.951">Thomas et al 2015</a>].</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="chd2-dis.TF.4.3"><p class="no_margin">Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see <a href="https://www.epilepsy.com/tools-resources/forms-resources#Epilepsy-Foundation-Toolbox" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Epilepsy Foundation Toolbox</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchd2disTrecommendedsurveillancefor"><div id="chd2-dis.T.recommended_surveillance_for" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with <i>CHD2-</i>Related Neurodevelopmental Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.T.recommended_surveillance_for/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.T.recommended_surveillance_for_lrgtbl__"><table><thead><tr><th id="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Neurologic</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor those w/seizures as clinically indicated & assess for new-onset seizures.</td><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">At each visit</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Development</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor developmental progress & educational needs.</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Psychiatric/</b>
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<br />
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<b>Behavioral</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess behavior for anxiety, attention, & aggressive or self-injurious behavior.</td></tr><tr><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Family/</b>
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<br />
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<b>Community</b>
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</td><td headers="hd_h_chd2-dis.T.recommended_surveillance_for_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobchd2dismolgenTA"><div id="chd2-dis.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>CHD2-Related Neurodevelopmental Disorders: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_chd2-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_chd2-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_chd2-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_chd2-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_chd2-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_chd2-dis.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/1106" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CHD2</i>
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</a>
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</td><td headers="hd_b_chd2-dis.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1106" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">15q26<wbr style="display:inline-block"></wbr>​.1</a>
|
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</td><td headers="hd_b_chd2-dis.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/O14647" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Chromodomain-helicase-DNA-binding protein 2</a>
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</td><td headers="hd_b_chd2-dis.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CHD2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHD2</a>
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</td><td headers="hd_b_chd2-dis.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CHD2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CHD2</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="chd2-dis.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobchd2dismolgenTB"><div id="chd2-dis.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for CHD2-Related Neurodevelopmental Disorders (<a href="/omim/602119,615369" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK333201/table/chd2-dis.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__chd2-dis.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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