Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation
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 t...
Saved in:
Published in: | Annals of neurology Vol. 79; no. 3; pp. 428 - 436 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Blackwell Publishing Ltd
01-03-2016
|
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | 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. ANN NEUROL 2016;79:428–436 |
---|---|
Bibliography: | University of Tübingen - No. AKF 297-0-0, S.Bi. ark:/67375/WNG-572K3D38-K No Epilep Foundation European Science Foundation/German Research Foundation - No. EuroEPINOMICS, H.L.; Le1030/11-1; No. P.N.; Nu50/8-1 istex:7DE2C4C717862923634E39E5DCC6A6C5777F8B44 German Federal Ministry for Education and Research - No. NGFNplus/EMINet, H.L., P.N.; No. 01GS08123; No. 01GS08120; No. IonNeurONet, H.L.; 01GM1105 ArticleID:ANA24580 German Research Foundation - No. WE4896/3-1, Y.G.W. German Society for Epileptology ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0364-5134 1531-8249 |
DOI: | 10.1002/ana.24580 |