Severe epilepsy syndromes of early childhood: the link between genetics and pathophysiology with a focus on SCN1A mutations.
Advances in genetics have increased our understanding of the underlying pathophysiologic mechanisms that cause severe epilepsy syndromes of early childhood. Many of the mutations associated with these syndromes are located in genes coding for ion channels or their accessory subunits, giving rise to the concept of epilepsy ;;channelopathies.'' In particular, the SCN1A gene coding for the pore-forming a-subunit of the voltage-gated sodium channel Na(V)1.1 appears to be a common target for epilepsy syndrome-specific mutations. An SCN1A mutation can potentially result in either a gain or loss of sodium channel function. Epilepsies linked to SCN1A mutations range from a relatively benign syndrome called generalized epilepsy with febrile seizures plus to severe childhood epilepsies such as severe myoclonic epilepsy of infancy (Dravet syndrome). The availability of genetic tests for SCN1A mutations is expanding awareness of the spectrum of diseases mediated by this gene and is beginning to permit genotype- phenotype correlations. Eventually, such information might enable clinicians to select an appropriate therapeutic regimen for patients with specific epilepsy gene mutations.
Stafstrom
Carl E
CE
University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA. stafstrom@neurology.wisc.edu
D001923:Brain Chemistry / Q000235:genetics; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006580:Genetic Carrier Screening; D005817:Genetic Counseling / Q000639:trends; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels