Congenital myasthenic syndrome in Israel: Genetic and clinical characterization

- Congenital myasthenic syndromes (CMS) are rare and diverse neuromuscular disorders. There are 20 known CMS-causing genes.
- Information about the genetic etiology is of the utmost importance for both diagnosis and treatment decisions.
- Next generation sequencing (NGS) is currently cost-prohibitive. Thus, mutation-targeted testing can assist in diagnosis.
- In our cohort of 45 ethnically-diverse CMS patients, mutations in RAPSN were the most common cause of CMS, followed by COLQ.
- Specific mutations in RAPSN, CHRNE and COLQ occur in specific ethnic groups and should be considered when CMS is suspected.

The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin. All medical records were reviewed and clinical data, genetic mutations and outcomes were recorded. Forty-five patients with genetic mutations in known CMS genes from 35 families were identified. Mutations in RAPSN were identified in 13 kinships in Israel. The most common mutation was c.-38A>G detected in 8 patients of Iranian and/or Iraqi Jewish origin. Four different recessive mutations in COLQ were identified in 11 kinships, 10 of which were of Muslim-Arab descent. Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort. Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations and should be taken into account when the diagnosis of a CMS is suspected.