title: 'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.
abstract: We previously identified a homozygous mutation in the Golgi SNAP receptor complex 2 gene (GOSR2) in six patients with progressive myoclonus epilepsy. To define the syndrome better we analysed the clinical and electrophysiological phenotype in 12 patients with GOSR2 mutations, including six new unrelated subjects. Clinical presentation was remarkably similar with early onset ataxia (average 2 years of age), followed by myoclonic seizures at the average age of 6.5 years. Patients developed multiple seizure types, including generalized tonic clonic seizures, absence seizures and drop attacks. All patients developed scoliosis by adolescence, making this an important diagnostic clue. Additional skeletal deformities were present, including pes cavus in four patients and syndactyly in two patients. All patients had elevated serum creatine kinase levels (median 734 IU) in the context of normal muscle biopsies. Electroencephalography revealed pronounced generalized spike and wave discharges with a posterior predominance and photosensitivity in all patients, with focal EEG features seen in seven patients. The disease course showed a relentless decline; patients uniformly became wheelchair bound (mean age 13 years) and four had died during their third or early fourth decade. All 12 cases had the same variant (c.430G>T, G144W) and haplotype analyses confirmed a founder effect. The cases all came from countries bounding the North Sea, extending to the coastal region of Northern Norway. 'North Sea' progressive myoclonus epilepsy has a homogeneous clinical presentation and relentless disease course allowing ready identification from the other progressive myoclonus epilepsies.
authors: Epilepsy Research Centre, University of Melbourne, Austin Health, Heidelberg, Australia.
authors: Lysa
authors: L
authors: Boissé Lomax
authors: Marta A
authors: MA
authors: Bayly
authors: Helle
authors: H
authors: Hjalgrim
authors: Rikke S
authors: RS
authors: Møller
authors: Annemarie M
authors: AM
authors: Vlaar
authors: Kari M
authors: KM
authors: Aaberg
authors: Iris
authors: I
authors: Marquardt
authors: Luke C
authors: LC
authors: Gandolfo
authors: Michèl
authors: M
authors: Willemsen
authors: Erik-Jan
authors: EJ
authors: Kamsteeg
authors: John D
authors: JD
authors: O'Sullivan
authors: G Christoph
authors: GC
authors: Korenke
authors: Bastiaan R
authors: BR
authors: Bloem
authors: Irenaeus F
authors: IF
authors: de Coo
authors: Judith M A
authors: JM
authors: Verhagen
authors: Ines
authors: I
authors: Said
authors: Trine
authors: T
authors: Prescott
authors: Asbjørg
authors: A
authors: Stray-Pedersen
authors: Magnhild
authors: M
authors: Rasmussen
authors: Danya F
authors: DF
authors: Vears
authors: Anna-Elina
authors: AE
authors: Lehesjoki
authors: Mark A
authors: MA
authors: Corbett
authors: Melanie
authors: M
authors: Bahlo
authors: Jozef
authors: J
authors: Gecz
authors: Leanne M
authors: LM
authors: Dibbens
authors: Samuel F
authors: SF
authors: Berkovic
mesh_terms: D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology; D002648:Child; D004569:Electroencephalography; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D009659:North Sea; D010641:Phenotype; D050766:Qb-SNARE Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C491344:GOSR2 protein, human; D050766:Qb-SNARE Proteins