PRRT2 variants and effectiveness of various antiepileptic drugs in self-limited familial infantile epilepsy

Abstract

Purpose: Self-limited familial infantile epilepsy (SFIE) is largely associated with variants in proline-rich transmembrane protein 2 (PRRT2). However, the detailed phenotype–genotype correlations are unclear, along with the efficacy of various antiepileptic drugs in the treatment of this epilepsy syndrome. In this study, we analysed the PRRT2 variants associated with SFIE in Chinese patients, and the efficacy of different antiepileptic drugs prescribed during follow-up.Methods: We retrospectively included 20 patients diagnosed with SFIE and reviewed their clinical characteristics, genetic variants, and treatment responses.Results: Eighteen of the 20 (90%) patients harboured the common heterozygous variant of PRRT2 c.649dupC p.(Arg217fs). One patient had two heterozygous variants of PRRT2, c.640G>C p.(Ala214Pro) and c.955G>T p.(Val319Leu), and the other patient harboured a novel c.606delA (p.Pro203Hisfs) variant. Nine patients who had first-line treatment of oxcarbazepine (OXC) became seizure-free. However, initial treatment with levetiracetam (LEV) or sodium valproate (VPA) in eight and three patients, respectively, was not effective even after increasing the dosage, and seizure-free status was only achieved after changing the treatment to OXC. The treatment responses suggested a significant difference (P < 0.001) between OXC and other anti-epileptic drugs.Conclusion: OXC as a sodium channel blocker may have a better effect than LEV and VPA in the treatment of PRRT2-associated SFIE. PRRT2 variants may be used as a biomarker to help select antiepileptic drugs for SFIE.