P164 – 2586: Congenital myasthenic syndrome in Israel: Genetic and clinical characterization

Abstract

Objective Congenital myasthenic syndromes (CMS) are a rare heterogeneous group of inherited neuromuscular disorders associated with distinctive clinical, electrophysiological and genetic abnormalities. Mutations in various genes of the neuromuscular junction may cause presynaptic, synaptic or postsynaptic defects. In this study, the genetic and clinical characteristics of Israeli patients with CMS were evaluated. Methods Twentysix patients with CMS from 16 independent families in whom genetic mutation was detected were diagnosed in two Israeli medical centers. Genetic evaluation was initially performed depending on patients' clinical symptoms and known CMS genes were sequenced. Patients of Jewish Iranian or Iraqi ethnic origin were screened directly for a known 38 A-G mutation in RAPSYN. In two patients, whole exome sequencing was analyzed. All patients' medical records were reviewed and their clinical data, electrophysiological studies and outcome were recorded. Results The diagnosis of CMS was confirmed in 26 patients of 16 families. Among these patients, 8 patients of 4 families had recessive mutations in COLQ, eight patients of 5 families, mutations in CHRNE, and eight patients of 5 families, mutations in RAPSN. CHRND was diagnosed in 2 patients from one family. The mean age of onset of clinical symptoms was 6 months. Ptosis, ophthalmoplegia and feeding problems were the most common symptoms. Conclusions RAPSYN and CHRNE are the most common causes of CMS in our cohort. The second most common cause is COLQ. Specific mutations in RAPSYN, CHRNE and COLQ are detected in unique ethnic populations in Israel.