Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation.
Ann Neurol
; 79(3): 428-36, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26677014
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.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.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.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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coreia
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Predisposição Genética para Doença
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Epilepsia Neonatal Benigna
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Polimorfismo de Nucleotídeo Único
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Canal de Sódio Disparado por Voltagem NAV1.6
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Ann Neurol
Ano de publicação:
2016
Tipo de documento:
Article