Further Evidence of Epilepsy Association with Inherited Myoclonus Dystonia Linked to Mutation in the Epsilon-Sarcoglycan Gene (SGCE) (P03.058)

OBJECTIVE: We report on a Tunisian family with MD related to a novel mutation in SCGE gene in which generalized epilepsy is a prominent feature. BACKGROUND: Epilepsy and/or EEG abnormalities have been initially considered as an exclusion criterion for the diagnosis of Myoclonus Dystonia (M-D). Report of two MD families associated with epilepsy questionned these criteria and suggested that epilepsy may be part of the phenotype linked to mutation of the SGCE gene. DESIGN/METHODS: The pedigree consists in 26 family members spanning three generations. Seven living individuals with clinical M-D were identified. Neurological examination, electrophysiological recordings and genetic testing were performed in 3 individuals. RESULTS: In the index case, his sister and his daughter, the clinical picture associated early upper limbs myoclonus with cervical dystonia (respectively at the age of 10, 6 and 3 year-old) and delayed generalized epilepsy (at the age of 32, 35 and 7 year-old). Electrophysiology recorded myoclonic bursts without cortical premyoclonus potential, negative C-reflex response and lack of giant somatosensory evoked potentials. Intercritical EEG showed spikes at the fronto-temporal region in the affected sister. A heterozygous splicing mutation c.662+1G>A in intron 5 of the SGCE gene was found in the three cases resulting in a skipping of exon 5. CONCLUSIONS: We report the third family in the literature with M-D associated with epilepsy related to a nonsense mutation of the SGCE. Clinical features of this pedigree with a new mutation are close to the clinical picture of myoclonic epilepsies. Expression of the epsilon-sarcoglycan in the cortex raises the question of a cortical pattern added to the known subcortical origin in M-D. This suggests that epilepsy, in some M-D families, is an extended phenotype of the SGCE mutation. Disclosure: Dr. Clot has nothing to disclose. Dr. Clot has nothing to disclose. Dr. Ben Djebara has nothing to disclose. Dr. Kacem has nothing to disclose. Dr. Gargouri has nothing to disclose. Dr. Clot has nothing to disclose. Dr. Clot has nothing to disclose. Dr. Leguern has nothing to disclose. Dr. Gouider has nothing to disclose.