Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil.
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Authors
Estephan, Eduardo de Paula
Zambon, Antonio Alberto
Marchiori, Paulo Eurípedes
da Silva, André Macedo Serafim
Caldas, Vitor Marques
Moreno, Cristiane Araújo Martins
Reed, Umbertina Conti
Töpf, Ana
Lochmüller, Hanns
Zanoteli, Edmar
Publication Date
2018-11Journal Title
Neuromuscul Disord
ISSN
0960-8966
Publisher
Elsevier BV
Volume
28
Issue
11
Pages
961-964
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Estephan, E. d. P., Zambon, A. A., Marchiori, P. E., da Silva, A. M. S., Caldas, V. M., Moreno, C. A. M., Reed, U. C., et al. (2018). Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil.. Neuromuscul Disord, 28 (11), 961-964. https://doi.org/10.1016/j.nmd.2018.08.007
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.
Keywords
Humans, Myasthenic Syndromes, Congenital, Disease Progression, Muscle Proteins, DNA Mutational Analysis, Phenotype, Mutation, Alleles, Adolescent, Adult, Child, Brazil, Female, Male
Sponsorship
European Commission (305121)
Medical Research Council (MR/N025431/2)
Identifiers
External DOI: https://doi.org/10.1016/j.nmd.2018.08.007
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287729
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
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