Objective: We endeavored to evaluate a cohort of patients diagnosed with SCN8A-related epilepsy in a multi-disciplinary clinic and to create a bio-repository. Methods: We recruited patients with epilepsy due to SCN8A variants at Children's National Medical Center, through family organizations, or SCN8A.net. Study procedures included medical record review, review of EEG and MRI data, clinical evaluation, the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), DNA extraction, and preparation of peripheral blood mononuclear cells. Results: Seventeen patients (9 months - 19 years) completed the study. Age at seizure onset was 1 day to 4 years old (median age 4 months). Epilepsy phenotype ranged from mild epilepsy to severe developmental and epileptic encephalopathy. Medications targeting the voltage-gated sodium channel were most often effective, while levetiracetam resulted in worsening seizures and/or developmental regression in 7/16 (p < 0.05). VABS-3 scores were below age expectations for most children; older children had lower scores. Neurological examination revealed hypotonia (13), spastic quadriparesis (1), ataxia (9), dyskinesia (2)/ dystonia (7), and four non-ambulatory. Conclusions: This is the first report of a large series of patients with epilepsy due to SCN8A variants evaluated in a single multi-disciplinary clinic. By utilizing a more comprehensive and consistent evaluation, we clarify specific seizure and epilepsy types, describe a distinct epilepsy phenotype in a patient with a nonsense variant, delineate patterns of developmental delay, language, and swallow function (specifically anomic aphasia and flaccid dysarthria), identify and characterize movement disorders, report common findings on physical exam, and demonstrate clinical worsening with levetiracetam.
- Epileptic encephalopathy
- Ion channel gene defects
- Neuropsychological assessment
ASJC Scopus subject areas
- Clinical Neurology