Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?
Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) can both arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel. GEFS+ refers to a familial epilepsy syndrome where at least two family members have phenotypes that fit within the GEFS+ spectrum. The GEFS+ spectrum comprises a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome. Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing and poor outcome. More than 70% of patients with Dravet syndrome have mutations of SCN1A; these include both truncation and missense mutations. In contrast, only 10% of GEFS+ families have SCN1A mutations and these comprise missense mutations. GEFS+ has also been associated with mutations of genes encoding the sodium channel beta 1 subunit, SCN1B, and the GABA(A) receptor gamma 2 subunit, GABRG2. The phenotypic heterogeneity that is characteristic of GEFS+ families is likely to be due to modifier genes. Interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype. Early recognition of Dravet syndrome is important as aggressive control of seizures may improve developmental outcome.
Scheffer
Ingrid E
IE
Department of Medicine, The University of Melbourne, Austin Health, Victoria, Australia. scheffer@unimelb.edu.au
Zhang
Yue-Hua
YH
Jansen
Floor E
FE
Dibbens
Leanne
L
D001923:Brain Chemistry / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004829:Epilepsy, Generalized / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics; D003294:Seizures, Febrile / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
C546279:GABRG2 protein, human; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C568242:SCN1A protein, human; C470379:SCN1B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit