Abstract
The majority of severe epileptic encephalopathies of early childhood are symptomatic
where a clear etiology is apparent. There is a small subgroup, however, where no etiology
is found on imaging and metabolic studies, and genetic factors are important. Myoclonic–astatic
epilepsy (MAE) and severe myoclonic epilepsy in infancy (SMEI), also known as Dravet
syndrome, are epileptic encephalopathies where multiple seizure types begin in the
first few years of life associated with developmental slowing. Clinical and molecular
genetic studies of the families of probands with MAE and SMEI suggest a genetic basis.
MAE was originally identified as part of the genetic epilepsy syndrome generalized
epilepsy with febrile seizures plus (GEFS+). Recent clinical genetic studies suggest that SMEI forms the most severe end of
the spectrum of the GEFS+. GEFS+ has now been associated with molecular defects in three sodium channel subunit genes
and a GABA subunit gene. Molecular defects of these genes have been identified in
patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been
found in the setting of large GEFS+ pedigrees, whereas, more severe truncation mutations arising 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.
Keywords
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Article info
Publication history
Accepted:
July 12,
2001
Received in revised form:
July 9,
2001
Received:
June 22,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
