Clinical characteristics and genetic analysis of patients with SCN1A gene pathological variant-related disorders: a single-center retrospective study

SCN1A Gene pathological variants can lead to a spectrum of epilepsy phenotypes ranging from mild genetic epilepsy with febrile seizures plus (GEFS+) to severe Dravet syndrome (DS). As most pathological variants are de novo variants, early prediction of phenotypes and prognosis is challenging, and the genotype-phenotype correlation remains unclear. We retrospectively analyzed the clinical and genetic data of 50 children with SCN1A variant-related epilepsy to explore the relationship between variant characteristics (location, in silico prediction scores), seizure characteristics, and phenotypes. This study included 50 children with SCN1A variant-related epilepsy, among whom 86.0% (43/50) had onset before the age of 1, 86.0% (43/50) exhibited fever sensitivity, and 68.0% (34/50) were accompanied by developmental delay; 36.0% (18/50) experienced status epilepticus(SE), 56.0% (28/50) had cluster seizures, and 48.0% (24/50) showed abnormal electroencephalogram(EEG) within one year of onset. Genetic analysis revealed that missense mutations accounted for 62.0% (31/50), with 78.0% (39/50) being de novo variants, and 24 previously unreported pathogenic variants were identified. The DS group (16 cases) had a significantly higher incidence of SE compared to the non-DS group (P = 0.041), while the non-DS group had a higher proportion of missense mutations (P = 0.014). Variant region analysis indicated that N-terminal variants were strongly associated with SE, and variants in the S2-S3/S3-S4 regions were prone to causing EEG abnormalities. In terms of treatment, the ketogenic diet was effective in 80.0% (4/5) of the children, while sodium channel blockers exacerbated seizures in 66.6% (4/6) of the children. The genotype-phenotype correlation in SCN1A-related epilepsy is crucial for early diagnosis and management: missense mutations are more prevalent in non-DS phenotypes, while DS phenotypes carry a higher risk of SE. Previously unreported variant sites expand the genetic spectrum. Ketogenic diet (KD) may be an effective treatment option, and the use of Sodium channel blocker(SCB) requires caution.