'North Sea' progressive myoclonus epilepsy: Phenotype of subjects with GOSR2 mutation

Lysa Boissé Lomax, Marta A. Bayly, Helle Hjalgrim, Rikke S. Møller, Annemarie M. Vlaar, Kari M. Aaberg, Iris Marquardt, Luke C. Gandolfo, Michèl Willemsen, Erik Jan Kamsteeg, John D. O'Sullivan, G. Christoph Korenke, Bastiaan R. Bloem, Irenaeus F. De Coo, Judith M.A. Verhagen, Ines Said, Trine Prescott, Asbjørg Stray-Pedersen, Magnhild Rasmussen, Danya F. VearsAnna Elina Lehesjoki, Mark A. Corbett, Melanie Bahlo, Jozef Gecz, Leanne M. Dibbens, Samuel F. Berkovic

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1146-1154
Number of pages9
Issue number4
Publication statusPublished or Issued - Apr 2013


  • GOSR2
  • creatine kinase
  • electroencephalography
  • progressive myoclonus epilepsy
  • scoliosis

ASJC Scopus subject areas

  • Clinical Neurology

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