Congenital Myasthenia Syndrome: Correlation between clinical features and genetics from North India

Objective: To describe the clinical features, genetics subtypes and outcome of children with Congenital Myasthenic Syndrome (CMS) from North India. Methodology: Study design: single-centre case series. Children with a diagnosis of CMS were identified from the clinic record, details of demography, clinical findings, investigations, and the therapeutic response was recorded in a case record proforma. Results: A total of 12 genetically confirmed cases of CMS were registered between the years 2012-2021 and included in the study. The three clinical phenotypes were observed: Marked ptosis and external ophthalmoplegia was seen among 8 (75%) children with CHRNE, limb-girdle weakness with mild ptosis and no ophthalmoplegia was observed in one patient each with DOK7, and CHRND gene. Marked weakness in the neonatal age, apnoea, ptosis, ophthalmoplegia and facial weakness was observed in one patient with COL6 gene among 12 children with CMS, 4 families had two affected siblings. The repetitive nerve stimulation test showed a decremental response in 8/12 (75%) cases. In children with AchR receptor defects with CHRNE, CHRND genes showed a good response to pyridostigmine therapy. Children with DOK7, COL6 and CHRND slow channel defects showed partial response to salbutamol. A single base pair deletion in the CHRNE gene at c.1327del p. Glu443LysfsTer64 was the most common genetic variant in this series. Conclusion: Ptosis, external ophthalmoplegia, recurrent respiratory infections are the most common presenting features of CMS. AchR receptor defect due to CHRNE gene variant is the most frequent CMS subtype and showed sustained response to pyridostigmine and salbutamol.