Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil

摘要

Mutations inRAPSNare an important cause of congenital myasthenic syndrome (CMS), leading to endplate acetylcholine receptor deficiency. We present threeRAPSNearly-onset CMS patients (from a Brazilian cohort of 61 CMS patients). Patient 1 and patient 2 harbor the mutation p.N88K in homozygosity, while patient 3 harbors p.N88K in compound heterozygosity with another pathogenic variant (p.V165M; c.493G?≥?A). At onset, patient 3 presented with more severe symptoms compared to the other two, showing generalized weakness and repeated episodes of respiratory failure in the first years of life. During adolescence, she became gradually less symptomatic and does not require medication anymore, presenting better long-term outcomes than patients 1 and 2. This case series illustrates the variability ofRAPSNearly-onset CMS, with patient 3, despite severe onset, revealing an almost complete reversal of myasthenic symptoms, not limited to apneic episodes. Moreover, it suggests thatRAPSNCMS may be underdiagnosed in non-European countries.