CHD2 – a 2016 update

Updates. Our “Beyond the Ion Channel” blog has been in existence for over 3 years, during which we have seen many advances in our knowledge of epilepsy genetics and done our best to share them with you. We hope that we have contributed to making epilepsy research more understandable. Recently, we have been pondering what we can do to make the emerging Epilepsiome knowledge base more useful for our readers, including clinicians, researchers, and families alike. Read further to see our first round of changes to our Epilepsiome Gene Pages that we have applied to our CHD2 Gene Page.

Schematic of CHD2 illustrating its functional (chromo, DEXDc, DNA-binding and ATP helicase) domains, the location of previously-reported variants and the unique variants in both cases and controls identified in this study (modified under a Creative Commons Licence from

Schematic of CHD2 illustrating its functional (chromo, DEXDc, DNA-binding and ATP helicase) domains, the location of previously-reported variants and the unique variants in both cases and controls identified in this study (modified with permission from

Let the changes begin. Our updated Epilepsiome Gene Pages will include the following features that we will add with the next round of reviews for each gene.

Improved navigation. New section headings and formatting allow you to more easily identify the information you seek.

New topics. We have started to add sections on inheritance, prevalence & penetrance; cell/animal models; the clinical perspective, including recurrence risk and therapy; variant interpretation; and research studies.

Reference links. Reference links in the text and a reference section at the bottom of the page allow you to more easily find a reference of interest.

CHD2. We started our changes with a relatively new player in the field, CHD2. Although CHD2 mutations have only been known to be associated with epilepsy for a few years, they seem to have an important role in the epileptic encephalopathies. Let’s point out a few changes that we have updated on CHD2. First, we have added a reference list, including a link to the recently published CHD2 GeneReviews page, as well as a description of the existing animal models. Second, we have reviewed the current literature on CHD2 as of February 2016. Not much changed in the world of CHD2 since our last update. Our updated CHD2 page can be found here.

Share your knowledge. If you have knowledge or an idea about a topic related to an epilepsy gene that you think we should share on our blog, let us know. We want the blog to be a way for us to communicate new information as rapidly as possible and to grow our community’s understanding and collaboration.

Elizabeth Dechene

Elizabeth DeChene is a senior genetic counselor in the Division of Genomic Diagnostics at the Children’s Hospital of Philadelphia. Elizabeth joined the Division in 2012, serving as the Project Coordinator for a study focused on understanding the use of exome sequencing in clinical care and later transitioning to a role in the clinical Genomic Diagnostic Laboratory. After obtaining her Master’s degree in Genetic Counseling at Brandeis University in 2004, Elizabeth focused in pediatric genetic disease at the Boston Children’s Hospital, providing clinical genetic counseling for a variety of genetic conditions and managing a research study on rare neuromuscular disease.

2 thoughts on “CHD2 – a 2016 update

  1. We recently identified a de novo heterozygous CHD2 variant in a nine-year-old male with a diagnosis of autism spectrum disorder (ASD). He had no known clinical seizures, but digital dense array electroencephalography (dEEG) found recurrent multifocal spike and slow wave discharges without any electroclinical associations or observations (“subclinical spikes”). MRI was unremarkable. The child’s neurobehavioral profile is consistent with “autonomic over-responsivity” leading to sudden mood changes and aggressive outbursts. Courtagen epiSEEK® sequencing panel identified the de novo variant: c.4492C>T; p.Gln1498Ter. Treatment of the child with lamotrigine led to decreased spike burden on dEEG, and has been associated with better attention and concentration in the school environment, along with a marked decrease in the intensity and duration of anger episodes. Based on the reports of CHD2 variants, the child may be prodromal for developing florid epilepsy as he grows, but it appears from previous reports that most probands presented with seizures at a much younger age. Thus, this case expands the phenotype of CHD2-related disease to include patients with neurodevelopmental disability without clinical epilepsy, but an epileptiform dEEG that may provide for a treatment target. The genetic lines between neurodevelopmental disabilities and epilepsies are becoming increasingly blurred, and large “neurodevelopmental disability” sequencing panels should consider expanded inclusion of epilepsy-related genes.

    • Thank you very much for sharing this interesting case. It is intriguing to see how our knowledge of the phenotypes associated with genetic conditions continues to expand. This case is a great reminder that we need to be mindful of this when pursuing genetic testing in both the research and clinical settings.

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