Abstract Details

Title 'North Sea' Progressive Myoclonus Epilepsy: Phenotype of Subjects with GOSR2 Mutation

Topic Epilepsy

Presentation(s) (-)

Poster/Presentation
Number 008

Objective

Background The PMEs are a group of devastating genetic disorders characterized by myoclonus, generalized tonic-clonic seizures, and progressive deterioration. We recently identified a novel homozygous mutation in the Golgi SNAP receptor complex 2 gene (GOSR2) in 6 patients with PME. To better define the syndrome, we analyzed the clinical and electrophysiological phenotype in 12 patients with GOSR2 mutation, including 6 new unrelated subjects.

Design/Methods We screened 159 patients with PME in whom no cause had been found despite appropriate investigations, for mutations in GOSR2. We then systematically collected and analyzed clinical data, EEGs, and laboratory investigations.

Results All 12 cases had the same variant (c.430G>T, G144W) and haplotype analyses confirmed a founder effect. All cases originated from countries bounding the North Sea. We found a homogenous clinical presentation with early onset ataxia (mean age 2 years), followed by myoclonic seizures (mean age 6.5 years), scoliosis, and chronically elevated creatine kinase (median 734IU). Other seizures types included absence and generalized tonic clonic seizures. All patients became wheelchair bound (mean age 13 years; range 8-27 years). There was a striking preservation of cognition in the context of severe motor disability. Electroencephalography revealed photosensitive generalized spike and wave discharges with a posterior predominance, with focal EEG features seen in 7 patients. At last evaluation, 4 patients were deceased (age range 24-32 years) due to respiratory compromise or status epilepticus.

Conclusions 'North Sea' PME is a novel clinical entity with a homogeneous presentation. Clinical clues for recognition amongst other PMEs are early ataxia around 2 years, myoclonus onset around 6 years, raised creatine kinase and the presence of scoliosis.

Authors/Disclosures
Lysa Boissé Lomax, MD (Queen'S University) PRESENTER	Dr. Boissé Lomax has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Boissé Lomax has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB, Eisai, Sunovion. Dr. Boissé Lomax has received personal compensation in the range of $0-$499 for serving as an Expert Witness for Correctional Service Canada. The institution of Dr. Boissé Lomax has received research support from UCB.
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Anna Maria M. Vlaar, MD, PhD	No disclosure on file
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Irene L. Katzan, MD (Cleveland Clinic, Neurology)	Dr. Katzan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring . The institution of Dr. Katzan has received research support from TEVA Pharmaceuticals.
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Bastiaan R. Bloem, MD, PhD (Radboud University Nijmegen Medical Centre)	No disclosure on file
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Samuel F. Berkovic, MD, FRACP (Epilepsy Research Centre)	No disclosure on file

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