Q&A: Genetic-based screening may provide insight into rare forms of epilepsy
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Genetic-based screening tests among children with epilepsy may provide knowledge into the clinical characteristics of molecular diagnoses of rarer forms of the disorder, researchers found.
SCN8A-related epilepsy is caused by pathogenic variants in the SCN8A gene, which can lead to a variety of neurological conditions, including mild to severe seizures, developmental and cognitive impairment, autism spectrum disorder and movement disorders, according to the Children’s Hospital of Philadelphia.
Researchers from Neurocrine Biosciences Inc. conducted a study among children aged 7 years and younger in the United States and Canada who had at least one or more unprovoked seizures. They analyzed genetic testing results, as well as patient demographic, clinical history and treatment information.
Healio spoke with Neurocrine Chief Medical Officer Eiry W. Roberts, MD, to gain insight on the study.
Healio: What was the aim of the study for you and your colleagues?
Roberts: We wanted to better understand the demographics, disease presentation, seizure history and treatment of pediatric patients with SCN8A-related epilepsies. Children living with rare pediatric epilepsies, such as SCN8A developmental and epileptic encephalopathy (SCN8A-DEE), are at a higher risk of sudden unexpected death in epilepsy or SUDEP. Unfortunately, there are currently no approved therapies for this form of pediatric epilepsy. Neurocrine is committed to advancing research and the development of potential new treatment options for children and adults with SCN8A-DEE.
Healio: What did you and your colleagues find?
Roberts: Data analysis demonstrated that 36 of the 17,843 children participating in the study had an SCN8A variant that was classified as pathogenic (P) or likely pathogenic (LP). Of 24 unique P/LP SCN8A variants identified, 14 were classified as P, and 10 were LP. In patients with a P/LP SCN8A variant, mean (± SD) age at seizure onset was 1.4 (± 1.4) years and mean age at testing was 2.1 (± 2.4) years.
We were also able to collect information regarding the types of seizures and developmental delays experienced by these patients. The most common type of seizure — reported by 50% of patients — was generalized onset motor, followed by 30% reporting focal onset seizures and 13.9% generalized non-motor seizures. We also found that the most common developmental delay was language. In addition, over half (58.3%) of patients were reported to have experienced at least one convulsive seizure in the last month, and almost half (44.5%) of patients experienced at least one prolonged seizure, over 5 minutes, in the last 6 months.
We also observed upon screening that 77.8% of patients were reported to be taking one to three antiseizure medications (ASMs), and almost one-fifth (19.4%) had previously discontinued one to three ASMs.
Healio: What are the clinical implications of these findings?
Roberts: Genetic screening-based studies such as this one may inform clinical trial design and provide insights into the clinical characteristics of patients with specific molecular diagnoses. Further analysis will clarify the role that variants identified in two or more epilepsy-associated genes play in shaping these results.
Healio: What more needs to be done in the future?
Roberts: It is essential that we continue advancing research around rare pediatric epilepsies such as SCN8A-DEE and support the testing and diagnosis of patients burdened by unprovoked seizures.
We are committed to supporting this ongoing effort, which is why Neurocrine Biosciences is a sponsor of and participant in Invitae’s Behind the Seizure program in the United States and Canada, which provides free access to comprehensive testing for epilepsy-related genetic variations to any child under 8 years old who has had an unprovoked seizure.
References:
- Demographic and clinical characteristics of pediatric patients with scn8a-related epilepsies: Results from a no-change epilepsy gene panel. https://cms.aesnet.org/abstractslisting/demographic-and-clinical-characteristics-of-pediatric-patients-with-scn8a-related-epilepsies--results-from-a-no-charge-epilepsy-gene-panel. Published Dec. 4, 2022. Accessed Dec. 19, 2022.
- SCN8A-related epilepsy. Children’s Hospital of Philadelphia. https://www.chop.edu/conditions-diseases/scn8a-related-epilepsy#:~:text=SCN8A%2DRelated%20Epilepsy%3F-,What%20is%20SCN8A%2DRelated%20Epilepsy%3F,disorders%20with%20or%20without%20epilepsy. Accessed Dec. 20, 2022.