title: Clinical correlations of mutations in the SCN1A gene: from febrile seizures to severe myoclonic epilepsy in infancy.
abstract: Mutations in the alpha-subunit of the first neuronal sodium channel gene SCN1A have been described in isolated patients with severe myoclonic epilepsy in infancy or Dravet syndrome and in families with generalized epilepsy with febrile seizures plus. To find phenotype/genotype correlations, we reviewed all published cases of mutations in SCN1A in addition to four new patients reported here. A total of 60 mutations were observed. Approximately 52% (31/60) are truncating mutations correlating with de novo cases of classical Dravet syndrome in 32 of 34 (94%) patients. Missense mutations in the pore-forming part constitute 27% (16/60) and correspond to a classical type in 12 of 16 (75%) patients. Missense mutations in the voltage sensor were present in 12% (7/60) and correlate with a clinical picture ranging from febrile seizures plus to severe myoclonic epilepsy in infancy. Outside these regions missense mutations are rare and account for only 10% (6/60), corresponding mostly with febrile seizures plus. These results illustrate that the clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy, and confirm the clinical experience that severe myoclonic epilepsy in infancy is the most severe form on this spectrum.
authors.affiliation: Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium.
authors.forename: Berten P G M
authors.initials: BP
authors.lastname: Ceulemans
authors.forename: Lieve R F
authors.initials: LR
authors.lastname: Claes
authors.forename: Lieven G
authors.initials: LG
authors.lastname: Lagae
mesh_terms: D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels