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Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation.
- Source :
-
Annals of neurology [Ann Neurol] 2016 Mar; Vol. 79 (3), pp. 428-36. Date of Electronic Publication: 2016 Feb 13. - Publication Year :
- 2016
-
Abstract
- Objective: Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as infantile convulsions and paroxysmal choreoathetosis (ICCA)-are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified as the major gene in all 3 conditions, found to be mutated in 80 to 90% of familial and 30 to 35% of sporadic cases.<br />Methods: We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed cliniconeurophysiological workup.<br />Results: In 3 families with a total of 16 affected members, we identified the same, cosegregating heterozygous missense mutation (c.4447G>A; p.E1483K) in SCN8A, encoding a voltage-gated sodium channel. A founder effect was excluded by linkage analysis. All individuals except 1 had normal cognitive and motor milestones, neuroimaging, and interictal neurological status. Fifteen affected members presented with afebrile focal or generalized tonic-clonic seizures during the first to second year of life; 5 of them experienced single unprovoked seizures later on. One patient had seizures only at school age. All patients stayed otherwise seizure-free, most without medication. Interictal electroencephalogram (EEG) was normal in all cases but 2. Five of 16 patients developed additional brief paroxysmal episodes in puberty, either dystonic/dyskinetic or "shivering" attacks, triggered by stretching, motor initiation, or emotional stimuli. In 1 case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortical involvement.<br />Interpretation: Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum of combined epileptic and dyskinetic syndromes.<br /> (© 2016 American Neurological Association.)
- Subjects :
- Child
Child, Preschool
Chorea diagnosis
Epilepsy, Benign Neonatal diagnosis
Female
Humans
Male
Mutation genetics
Chorea genetics
Epilepsy, Benign Neonatal genetics
Genetic Predisposition to Disease genetics
NAV1.6 Voltage-Gated Sodium Channel genetics
Polymorphism, Single Nucleotide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1531-8249
- Volume :
- 79
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Annals of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 26677014
- Full Text :
- https://doi.org/10.1002/ana.24580