title: Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.
abstract: We recently reported mutations in the sodium channel gene SCN2A in two families with benign familial neonatal-infantile seizures (BFNISs). Here, we aimed to refine the molecular-clinical correlation of SCN2A mutations in early childhood epilepsies. SCN2A was analyzed in 2 families with probable BFNIS, 9 with possible BFNIS, 10 with benign familial infantile seizures, and in 93 additional families with various early childhood epilepsies. Mutations effecting changes in conserved amino acids were found in two of two probable BFNIS families, in four of nine possible BFNIS families, and in none of the others. Our eight families had six different SCN2A mutations; one mutation (R1319Q) occurred in three families. BFNIS is an autosomal dominant disorder presenting between day 2 and 7 months (mean, 11.2 +/- 9.2 weeks) with afebrile secondarily generalized partial seizures; neonatal seizures were not seen in all families. The frequency of seizures varied; some individuals had only a few attacks without treatment and others had clusters of many per day. Febrile seizures were rare. All cases remitted by 12 months. Ictal recordings in four subjects showed onset in the posterior quadrants. SCN2A mutations appear specific for BFNIS; the disorder can now be strongly suspected clinically and the families can be given an excellent prognosis.
authors.affiliation: Epilepsy Research Centre and Department of Medicine, University of Melbourne, Austin Health, Victoria, Australia. s.berkovic@unimelb.edu.au
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.forename: Lucio
authors.initials: L
authors.lastname: Giordano
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kaplan
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Grinton
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Dean
authors.forename: Laura
authors.initials: L
authors.lastname: Bordo
authors.forename: Bree L
authors.initials: BL
authors.lastname: Hodgson
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography / Q000379:methods; D020936:Epilepsy, Benign Neonatal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; D015222:Sodium Channels