CHRNE-related congenital myasthenic syndrome in Iran: Clinical and molecular insights

Variants in the CHRNE gene can lead to a condition called congenital myasthenic syndrome (CMS), which affects the neuromuscular junction (NMJ). CHRNE mutations are the most common cause of CMS. Seventy-seven patients with a possible diagnosis of CMS were referred to the neuromuscular clinic of Shariati Hospital affiliated with the Tehran University of Medical Sciences. We performed whole-exome sequencing (WES) to determine the underlying defect in a group of individuals with a possible diagnosis of CMS. Clinical features and morphological and molecular data on 33 patients with mutations in CHRNE were described. Age of onset, age at diagnosis, consanguinity, family history, motor milestone delay, ophthalmoparesis, generalized fatigue, dysphagia, neurophysiologic findings, and response to treatment of the patients were assessed. Nineteen CHRNE variants including 10 novel ones were identified. The most common mutations were c.1327del; (p.Glu443LysfsTer64) in four different families and c.1252-1267dup; (p.Cys423SerfsTer38) in three families. Clinical onset was mostly at birth or under one year with bilateral fatigable ptosis, ophthalmoplegia, bulbar weakness, and proximal muscle weakness. All patients were treated with pyridostigmine ± salbutamol, which resulted in improvement of motor function, dysphagia, and breathing.