The spectrum of SCN1A-related infantile epileptic encephalopathies.
The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.
Harkin
Louise A
LA
Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia.
McMahon
Jacinta M
JM
Iona
Xenia
X
Dibbens
Leanne
L
Pelekanos
James T
JT
Zuberi
Sameer M
SM
Sadleir
Lynette G
LG
Andermann
Eva
E
Gill
Deepak
D
Farrell
Kevin
K
Connolly
Mary
M
Stanley
Thorsten
T
Harbord
Michael
M
Andermann
Frederick
F
Wang
Jing
J
Batish
Sat Dev
SD
Jones
Jeffrey G
JG
Seltzer
William K
WK
Gardner
Alison
A
Sutherland
Grant
G
Berkovic
Samuel F
SF
Mulley
John C
JC
Scheffer
Ingrid E
IE
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004828:Epilepsies, Partial / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010290:Parents; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels