The "plus" side of epilepsy phenotyping

The first clinical description of generalized epilepsy with febrile seizures plus (GEFS+) by Scheffer and Berkovic1 in their landmark Brain article of 1997 represented a major step forward in the understanding of the genetic basis of the epilepsies. Coming 2 years after their identification, with collaborators, of the genetic basis for a relatively homogenous syndrome, autosomal dominant nocturnal frontal lobe epilepsy, the detailed phenotypic description of a single large Australian family with heterogeneous febrile seizure plus epilepsy phenotypes and a clear dominant pattern of inheritance put a novel perspective on genotype–phenotype relationships in the epilepsies.2 Shortly after, the SCN1A and SCN1B genes were linked to the syndrome, and subsequently the last 2 decades has confirmed that the majority of epilepsy genes show phenotypic heterogeneity and the majority of syndromes reveal genetic heterogeneity.3 Why one individual in a GEFS+ family has a severe developmental and epileptic encephalopathy such as Dravet syndrome and another has simple self-limited febrile seizures is unknown, but is likely to be determined by other genetic factors influencing the SCN1A, or other major genes identified in a family.
Source: Neurology - Category: Neurology Authors: Tags: All Clinical Neurology, All Epilepsy/Seizures, Generalized seizures, Partial seizures EDITORIALS Source Type: research