Genetic Spectrum and Its Treatment Implications In Congenital Myasthenic Syndrome

INTRODUCTION : CMS is a group of diverse inherited disorders of neuromuscular transmission presenting with motor delay and associated fatigable weakness. We reviewed the phenotypic and genotypic characteristics of CMS patients for better understanding of long term outcome. METHOD : We performed a multicentric study across India from 2015 to 2021,enrolled 72 patients with CMS and studied their clinical characteristics, diagnostic modalities, genetic results and treatment outcomes. RESULTS : Out of 72, male: female ratio 1:1. Median age of presentation 13 years (0-46 years). The most common presenting complaints were ptosis (50%), ophthalmoplegia (28%), motor weakness (28%), motor developmental delay (24%), respiratory involvement (14%) and bulbar symptoms with nasal regurgitation and feeding difficulties (7%). Many patients had a combination of these complaints. The genetic mutations were CHRNE (44), COLQ (10), DOK7 (6), CHRNA1 (3), RAPSN (2), MUSK (2), GFPT1 (2), CHRND (1), DAPGT1 (1) and AGRN (1). Pyridostigmine was used for treatment in 50 patients, 30 had good response while 2 COLQ, 1 DOK7 and 3 CHRNE worsened with it. 14/50 had no to partial benefit. Salbutamol was used in 27 patients, 20 had good response while 2 worsened and 5 had no benefit. Out of 6 patients treated with Fluoxetine, 3 with COLQ and 1 with DOK7 had good response. Two children with COLQ died at home of respiratory failure.

CONCLUSION : Genetic results have therapeutic implications in CMS as compared to most other neuromuscular disorders.