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Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation.
Gardella, Elena; Becker, Felicitas; Møller, Rikke S; Schubert, Julian; Lemke, Johannes R; Larsen, Line H G; Eiberg, Hans; Nothnagel, Michael; Thiele, Holger; Altmüller, Janine; Syrbe, Steffen; Merkenschlager, Andreas; Bast, Thomas; Steinhoff, Bernhard; Nürnberg, Peter; Mang, Yuan; Bakke Møller, Louise; Gellert, Pia; Heron, Sarah E; Dibbens, Leanne M; Weckhuysen, Sarah; Dahl, Hans Atli; Biskup, Saskia; Tommerup, Niels; Hjalgrim, Helle; Lerche, Holger; Beniczky, Sándor; Weber, Yvonne G.
Afiliación
  • Gardella E; Danish Epilepsy Center-Filadelfia, Dianalund, Denmark.
  • Becker F; Institute of Regional Health Research, University of South Denmark, Odense, Denmark.
  • Møller RS; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Schubert J; Danish Epilepsy Center-Filadelfia, Dianalund, Denmark.
  • Lemke JR; Institute of Regional Health Research, University of South Denmark, Odense, Denmark.
  • Larsen LH; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  • Eiberg H; Institute of Human Genetics, University Hospitals, University of Leipzig, Leipzig, Germany.
  • Nothnagel M; Amplexa Genetics, Odense, Denmark.
  • Thiele H; RC-LINK, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Altmüller J; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Syrbe S; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Merkenschlager A; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Bast T; Department of Woman and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
  • Steinhoff B; Department of Woman and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
  • Nürnberg P; Epilepsy Center Kork, Kork, Germany.
  • Mang Y; Epilepsy Center Kork, Kork, Germany.
  • Bakke Møller L; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Gellert P; Wilhelm Johannsen Center for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Heron SE; Danish Epilepsy Center-Filadelfia, Dianalund, Denmark.
  • Dibbens LM; Danish Epilepsy Center-Filadelfia, Dianalund, Denmark.
  • Weckhuysen S; Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
  • Dahl HA; Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
  • Biskup S; Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
  • Tommerup N; Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
  • Hjalgrim H; Neurogenetics Group, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium.
  • Lerche H; Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
  • Beniczky S; Amplexa Genetics, Odense, Denmark.
  • Weber YG; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Ann Neurol ; 79(3): 428-36, 2016 Mar.
Article en En | MEDLINE | ID: mdl-26677014
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Corea / Predisposición Genética a la Enfermedad / Epilepsia Benigna Neonatal / Polimorfismo de Nucleótido Simple / Canal de Sodio Activado por Voltaje NAV1.6 Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Ann Neurol Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Corea / Predisposición Genética a la Enfermedad / Epilepsia Benigna Neonatal / Polimorfismo de Nucleótido Simple / Canal de Sodio Activado por Voltaje NAV1.6 Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Ann Neurol Año: 2016 Tipo del documento: Article País de afiliación: Dinamarca