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

Accepted version
Peer-reviewed

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Type

Article

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Authors

Estephan, Eduardo de Paula 
Zambon, Antonio Alberto 
Marchiori, Paulo Eurípedes 
da Silva, André Macedo Serafim 
Caldas, Vitor Marques 

Abstract

Mutations in RAPSN are an important cause of congenital myasthenic syndrome (CMS), leading to endplate acetylcholine receptor deficiency. We present three RAPSN early-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 of RAPSN early-onset CMS, with patient 3, despite severe onset, revealing an almost complete reversal of myasthenic symptoms, not limited to apneic episodes. Moreover, it suggests that RAPSN CMS may be underdiagnosed in non-European countries.

Description

Keywords

Congenital myasthenia, Congenital myasthenic syndrome, RAPSN, neuromuscular, rapsyn, Adolescent, Adult, Alleles, Brazil, Child, DNA Mutational Analysis, Disease Progression, Female, Humans, Male, Muscle Proteins, Mutation, Myasthenic Syndromes, Congenital, Phenotype

Journal Title

Neuromuscul Disord

Conference Name

Journal ISSN

0960-8966
1873-2364

Volume Title

28

Publisher

Elsevier BV
Sponsorship
European Commission (305121)
Medical Research Council (MR/N025431/2)