Clinical and molecular genetics of myoclonic-astatic epilepsy and severe myoclonic epilepsy in infancy (Dravet syndrome)

The majority of severe epileptic encephalopathies of early childhood are sy mptomatic where a clear etiology is apparent. There is a small subgroup, ho wever, where no etiology is found on imaging and metabolic studies, and gen etic factors are important. Myoclonic-astatic epilepsy (MAE) and severe myo clonic epilepsy in infancy (SMEI), also known as Dravet syndrome, are epile ptic encephalopathies where multiple seizure types begin in the first few y ears of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a gen etic basis. MAE was originally identified as part of the genetic epilepsy s yndrome generalized epilepsy with febrile seizures plus (GEFS(+)). Recent c linical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defe cts in three sodium channel subunit genes and a GABA subunit gene. Molecula r defects of these genes have been identified in patients with MAE and SMEI . Interestingly, the molecular defects in MAE have been found in the settin g of large GEFS(+) pedigrees, whereas, more severe truncation mutations ari sing de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.