Congenital Myasthenic Syndrome: Long‐Term Outcomes up to 60 Years, Molecular Characterization, and Eight Novel Variants

Congenital myasthenic syndrome (CMS) refers to a rare heterogeneous group of hereditary disorders characterized by fatigue and muscle weakness due to impairment in neuromuscular transmission. A total of 40 genes have been identified in the pathogenesis of CMSs. The study assessed 22 patients (14 females and 8 males) with CMS of childhood onset with their phenotypes and genotypes. Genetic analysis revealed variations in the following eight genes: CHRNE, DOK7, GFPT1, COLQ, SLC25A1, CHAT, MUSK, and MYO9A. Eight novel variations were detected involving SLC25A1, MUSK, DOK7, GFPT1, and CHRNE. The median age was 14 years (range: 0.5-67 years). The median age of onset of symptoms was 8 months (range: 0-16 years). The longest time after the onset of symptoms was 62 years. The most common initial symptoms were weakness of extremities (n = 9) and ptosis (n = 8). Respiratory symptoms were present in 11 patients (50%), which showed progression, multiphasic disease course, and amelioration in 45.4%, 18.1%, and 36.3% of patients, respectively. Motor symptoms showed a progressive worsening in 68.1%, stationary course in 13.6%, multiphasic disease course in 13.6%, and amelioration in 4.5% of patients. Thanks to next-generation sequencing, diagnoses of CMS have been increasing over the recent years; so has the number of novel variants.