To identify and describe the phenotypical and  genotypical characterstics of Congenital Myasthenic Syndromes in Saudi Arabia.

Congenital myasthenic disorders are a group of rare hereditary disorders affecting the neuromuscular junction with heterogenous phenotypes and numerous genotypes. Few case reports and case series have been reported in the GCC region and included mutations in CHRNE, SLC25A1, COLQ, ALG2, VAMP1 and DOK7 genes.

This is a single center retrospective cross sectional study utilized CMS data from clinical practitioners and the institutional genetic data base. 42 patients were initially identified. However, 18 patients were excluded due to either absence of clinical diagnosis, lack of genetic confirmation, or insufficient clinical data. Ultimately, 24 patients met criteria.

This study includes 24 patients with clinically and genetically confirmed CMS. 62% were males, and 37% were females. All were ethnically Arab, 20% were from the northern region, 29% were from the central region, and the rest were equally distributed across other regions. Disease onset occurred in infancy in 60%, childhood 36%. Mutations in 12 different genes were identified including CHRNE (28%), PREPL (20%), COLQ (8%), ALG2 (8%), DOK7 (4%), SCN4A (4%), RAPSN (4%), GFPT1 (4%), SLC5A7(4%), ARGN (4%), VAMP (4%),  and PRX (4%). Common clinical variables included limb weakness (70%), ptosis/diplopia (75%), and Respiratory symptoms (40%). Fatiguability was reported in 83%. 37% were underweight at presentation, and mean height SD was 35 percentile.

There is significant heterogenicity of CMS genotypes in Saudi Arabia. Of the included cases, majority of patients were from the central and northern regions, however patients from all major regions of SA were identified. Fatiguability, limb weakness, and ocular findings were the most commonly reported clinical findings. Short stature and low body mass were common upon presentation. This study further emphasizes the importance genetic testing in suspected cases of CMS.