Key epilepsy gene gets further phenotypic delineation

In this issue of Neurology®, a study from a neurogenetics group in Belgium¹ traces the genetic defect in a 4-generation Bulgarian family with febrile seizures and epilepsy associated with varying degrees of cognitive impairment related to a microdeletion encompassing the SCN1A gene. Typically, SCN1A mutations that predict truncation or a highly abnormal protein (including microdeletions) are associated with severe childhood epileptic encephalopathies, specifically the syndrome of severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and related disorders.^2,3

Dravet syndrome is an epileptic encephalopathy with low reproductive fitness due to the usual outcome of moderate to severe intellectual disability and increased mortality in childhood. The novelty in the report by Suls et al.¹ is the fact that the epileptic syndrome and the associated intellectual disability were not so severe to prevent procreation, which is counter to other currently published cases with such microdeletions. The observations are framed in the context of Dravet syndrome, which is the usual consequence of haploinsufficiency of SCN1A, whether due to a truncation mutation …