A novel de novo SCN1A missense mutation in Severe Myoclonic Epilepsy Borderland.

In this report we describe a novel missense SCN1A mutation in a patient affected by Severe Myoclonic Epilepsy Borderland (SMEB). This three and a half year-old female patient experienced prolonged febrile seizures at the age of 14 months, followed by generalized tonic-clonic seizures, atonic seizures, atypical absences almost in a cluster and triggered by fever. Cognitive and motor development was normal. The case was suggestive for SMEB. SCN1A analysis revealed an unknown de novo point mutation: a heterozygous replacement of nucleotide G with nucleotide T in position 4183 of the coding region of the gene (c.4183 G>T) in exon 21. This mutation causes the replacement of aspartic acid with tyrosine in 1395 (p.D1396Y). Even if other SCN1A missense mutations localized in the same region are associated to SMEB, a definite genotype-phenotype correlation has not yet been found, probably because other factors are involved in the pathogenesis of this type of epilepsy.