Abstracts

Rationale: Golgi SNAP receptor complex member 2 (GOSR2) is a SNARE protein involved in Golgi vesicle transportation. Homozygous mutations in GOSR2 (c430G >T) have been linked to North Sea progressive myoclonus epilepsy (NSPME) with normal muscle biopsy while compound heterozygous mutations in GOSR2 were recently described with different clinical phenotypes including progressive myoclonic epilepsy (PME) and severe muscular dystrophy. Heterozygous GOSR2 mutations are rare with only a handful of cases described in the literature with both PME and muscular dystrophy.

Methods: We describe a 3-year-old boy with heterozygous bi-allelic GOSR2 mutations (c 430G >T and c336+ 1 G >A). He presented with motor delay and was initially diagnosed with muscular dystrophy. After he presented with myoclonic absence epilepsy, the correct molecular diagnosis was identified. We describe EEG findings, seizure semiology, MRI and muscle biopsy.

Results: A year-old boy with no significant family history and normal birth presented with hypotonia, motor delay, and a brief episode of generalized shaking before the age of 6 months. Evaluation was unremarkable and physical and occupational therapy was started. A brain MRI at 14 months revealed mild left posterior plagiocephaly. Creatine kinase level was elevated (9,116 U/L) which subsequently lead to neuromuscular evaluation. He had a myopathic EMG. Muscle biopsy at 17 months revealed a dystrophic process with absent dystroglycan staining indicative of severe dystrophic myopathy with abnormal immunostaining of sarcolemmal proteins. However, neuromuscular gene panel testing was negative.

At the age of 25-months, he developed new episodes of head nods and drop attacks occurring more frequently during drowsiness and early sleep. Video-electroencephalogram (V-EEG) showed frequent 2-3 Hz generalized spike-wave discharges and high amplitude disorganized slow background activity consistent with possible epileptic encephalopathy. In addition, multiple seizure types were captured including absence; myoclonic with jerks of both arms; and atonic with drop attacks. Levetiracetam was started, but then switched to ethosuximide and sodium valproate with improved seizure control. A follow up EEG after treatment showed occasional bilateral shifting occipital spikes and occipital intermittent rhythmic delta activity (OIRDA). A commercial epilepsy gene panel revealed heterozygous trans mutations in GOSR2.

Conclusions: Autosomal recessive GOSR2 disorder is a rare disorder that encompasses both muscular dystrophy as well as epileptic encephalopathy. The gene should be included in both gene panels for neuromuscular as well as epilepsy syndromes. Our case also revealed associated absence and myoclonic epilepsy and expands the phenotypic spectrum of this rare disorder.

Funding: Please list any funding that was received in support of this abstract.: NA.