SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures

Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A mm gene, We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy - including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI - mostly without myoclonic-astatic seizures - were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5G -> C) and a missense mutation in the conserved pore region (40736 C -> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.