Analiza genetyczna rodzinnej, samoograniczającej się epilepsji niemowląt spowodowanej zmianami w genie PRRT2 u pacjentów indyjskich

INTRODUCTION: Self-limiting familial infantile epilepsy (SeLFIE) is an epilepsy syndrome characterized by recurrent focal motor seizures. It follows an autosomal dominant inheritance pattern. Phenotypic and genetic heterogeneity of SeLFIE are associated with the PRRT2 gene, with the most common mutation being the frameshift variant c.649dupC. This study broadens the mutation spectrum of PRRT2 associated with SeLFIE. OBJECTIVE: To analyze the genotypic and phenotypic spectrum of SeLFIE in relation to PRRT2 gene variants. METHODOLOGY: A cohort of fifteen pediatric probands diagnosed with SeLFIE was clinically evaluated and genetically screened for PRRT2 mutations using Sanger sequencing. Pathogenicity of the variants was classified according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Twelve out of fifteen patients (80%) harbored the common hotspot frameshift mutation c.649dupC (p.Arg217Profs*8) in the PRRT2 gene. Three exhibited different PRRT2 gene variants, including a frameshift c.649delC (p.Arg217Glufs*12), a missense c.696C>G (p.His232Gln), and a nonsense variant c.649C>T (p.Arg217*). Initially, all patients were treated with either sodium channel blockers or in combination with other antiseizure medications like levetiracetam/sodium valproate. Later, changed to sodium channel blockers (oxcarbazepine, phenytoin or carbamazepine) in all cases and achieved seizure-free status in all the patients. CONCLUSION: Our study findings broaden the variant spectrum of PRRT2 in SeLFIE, while oxcarbazepine remains highly effective treatment for seizure control. Early-stage genetic analysis plays a crucial role in minimizing unnecessary diagnostic procedures and in guiding more effective disease management in SeLFIE patients.