Prognostic challenges of SCN1A genetic mutations: report of two children with mild features

Mutations in the gene encoding the α-1 subunit of the voltage-gated sodium channel (SCN1A) are associated with variable but usually severe clinical course, both for the epileptic seizures and the cognitive impairment. The purpose of the present study was to retrospectively review two patients affected by seizures and two different types of SCN1A gene mutations (microdeletion and point mutation). The children (a 4-year-old girl and a 3-year-old boy) were affected by generalized tonic-clonic seizures and myoclonic jerks plus unilateral seizures, respectively. Genetic analyses showed, in the girl, the presence of a 4 MB deletion involving SCN1A and four other genes, and a point mutation in the boy. Both the patients showed a mild clinical course, with a good pharmacological control of the crises and sufficient scholastic performances. At present, the role of the combination of SCN1A mutations and the related clinical manifestations is not very clear. Prognostic counseling is particularly challenging given that, in many cases, the clinical course of these patients is independent of the genotype and its severity is difficult to predict.