Clinical and genetic analysis of epilepsy in children with SCN8A gene variants

To analyse the clinical and genetic characteristics of children with epilepsy associated with SCN8A gene variants.

High-throughput whole-exome sequencing was performed on children suspected of having gene variant-related epilepsy. A total of 14 children with seizures caused by SCN8A gene variants were identified. A retrospective analysis was conducted to collect and summarise the medical records and genetic results of these children.

Eleven cases were identified with de novo variants and three with inherited heterozygous variants. The earliest age of onset was 10 min after birth, and the maximum age of onset was 2 years. Three patients were treated with a single drug, four were treated with two anti-seizure medicines (ASMs), seven were treated with three or more ASMs and two were treated with a ketogenic diet, but the efficacy was not satisfactory. Eight patients responded to sodium channel blockers, with doses ranging from higher than the standard paediatric dosage. Except for one case with a normal electroencephalogram, all others showed abnormalities, mainly characterised by multifocal and widespread discharges.

Typically, SCN8A gene variants cause early-onset childhood epilepsy, often within the first year of life, even in the neonatal period, and most cases are caused by de novo variants. Sodium channel blockers show some efficacy, but often require higher doses, and single-drug therapy is usually insufficient. The clinical phenotype of de novo variants is severe, with frequent seizures. Most patients still experience seizures despite treatment with 3-4 drugs, and focal or focal secondary generalised seizures are common. Seizure types such as spasms and myoclonus are rare.