Broad Clinical and Genetic Spectrum of Scn1a Mutation: A Multicenter Study From The Eastern Mediterranean Region of Turkey

Objectives SCN1A mutations can be seen in a broad spectrum changing from simple febrile seizures to severe myoclonic epilepsy of infancy (SEMI). The purpose of the study is to describe the clinical characteristics of Turkish children with SCN1A mutations as well as possible genotype-phenotype relationships.

Methods We thoroughly investigated demographic, clinical, and genetic data of 56 patients with SCN1A mutations from 4 different Pediatric Neurology Centers in the Eastern Mediterranean region of Turkey.

Results Among the 56 patients, 30(53.5 %) were girls, with a mean age of 8.1 ±6.75 years (13 months-24 years). Thirty-five(62.5%) patients had their first seizure during the course of an infection and 11 had after vaccination.The mean age of onset of seizure was 8.08± 4.47 months (1-26) and 90% of all patients had seizure onset under 12 months of age. The time from the first seizure to the genetic diagnosis ranged from 1 month to 20 years. 31 patients were diagnosed with SMEI, 10 with borderline SMEI, 2 with refractory epilepsy, 9 with recurrent FS, and 4 with febrile convulsion plus generalized epilepsy. Eight novel mutations in the SCN1A gene were identified. 30 of the patients had parental genetic screening and 17 had de novo mutation(SMEI:8,SMEB:5). Conclusions The present study showed that the age of onset of seizures was less than 1 year in 90% of the cases with different clinical phenotypes in SCN1A pathogenic variants. Being aware of this clinical spectrum and early onset of seizures is important for the early genetic diagnosis.