CHD2 variants were first reported in relation to autosomal dominant epileptic encephalopathies in 2013 (PMID:23708187). CHD2 alters gene expression by affecting chromatin regulation and acetylation. Patients with variants in CHD2 have been reported to have intellectual disability ranging in severity, autism spectrum disorder, seizures (including generalized myoclonic, atonic, bilateral tonic-clonic, etc.), myoclonus, status epilepticus, and ataxia. The ClinGen Epilepsy GCEP decided to curate variants in this gene for “complex neurodevelopmental disorder” to encompass the variability in severity, age of onset, and clinical presentations.
There are 10 unique variants (nonsense, frameshift, splice-site, and missense) reported in 10 probands in 3 publications (PMIDs:23934111, 23708187, 24207121) included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.
This gene-disease relationship is also supported by functional alteration of mouse neuronal progenitor cells (PMIDs:25786798).
In summary, there is definitive evidence to support the gene-disease relationship between CHD2 and autosomal dominant complex neurodevelopmental disorder. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on July 18, 2018. As of July 2022, this record underwent administrative updates to include an evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.