Quantitative Biology Colloquium
Epilepsy is one of the most common childhood neurological conditions affecting roughly 1% of children younger than the age of 15 years. Epileptic events that occur early in a child’s life can range in severity from ‘benign’ instances where a child outgrows their seizures to more severe cases with drug-resistant seizures. In fact, there are over 50 forms of early infantile epileptic encephalopathies (EIEE) caused by different genes several of which are within voltage-gated ion channels such as SCN8A. SCN8A variants are associated with intractable epilepsy beginning in infancy with seizure onset occurring within the first 18 months of life. The phenotypic spectrum of SCN8A also ranges from mild to severe with onset of developmental delay occurring anywhere from just after birth to just after seizure onset. It is currently unknown which variants lead to benign or severe developmental outcomes. Current in silico variant prediction models, like PolyPhen-2, are being used to predict the pathogenicity of variants based on evolutionary conservation, however these tools often miss the mark. Finding patterns and trends in the variant position and developmental acquisition in these children are key in understanding SCN8A-related disorders.