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Title
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Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Annals of neurology. - Boston, Mass.
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Publication
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Boston, Mass.
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2016
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ISSN
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0364-5134
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DOI
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10.1002/ANA.24580
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Volume/pages
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79
:3
(2016)
, p. 428-436
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ISI
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000371896800009
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Pubmed ID
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26677014
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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