Familial SCN1A missense mutation over three generations, from febrile seizures to severe myoclonic epilepsy in infancy

Abstract

Mutations of the sodium channel alpha subunit type 1 gene (SCN1A) gene, encoding the voltage gated sodium channel alpha-subunit, represent the most frequent genetic cause of severe myoclonic epilepsy in infancy (SMEI). So far over 250 SMEI related SCN1A mutations have been identified of which 95% are considered de novo. We report a familial SCN1A missense mutation over three generations with extremely variable phenotypes, from simple febrile seizures to SMEI. Severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome is an age-dependent epileptic en- cephalopathy with onset during the first year of life. Common manifestations of the disorder are often pro- longed hemiclonic or generalized tonic-clonic seizures, usually associated with fever, in previously healthy in- fants with normal psychomotor development. Inter- ictal electroencephalography (EEG) shows no sign of epileptic activity in the early course of the disease. The condition evolves with a variety of afebrile or fever- induced seizure types (myoclonic, atonic, absence and partial seizures) in the second year of life. Develop- mental stagnation occurs with many children showing ataxia and slowing in speech development; cognitive outcome is poor with a high risk of mental retarda-