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J Pediatr Genet 2023; 12(03): 258-262
DOI: 10.1055/s-0041-1728745
Case Based Review

X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy

Andreia Carvalho 
1   Neurology Department, Centro Hospitalar de Vila Nova de Gaia–Espinho, Portugal
,
Carmen Costa
2   Pediatric Neurology Department, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
,
Miguel Pinto
3   Neuropathology Unit, Hospital de Santo António - Centro Hospitalar Universitário do Porto, Porto, Portugal
,
Ricardo Taipa
3   Neuropathology Unit, Hospital de Santo António - Centro Hospitalar Universitário do Porto, Porto, Portugal
4   Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
,
Ana Gonçalves
4   Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
5   Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal
,
Márcia E. Oliveira
4   Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
5   Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal
,
Sofia Ferreira
6   Pulmonology Department, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
,
Joana Afonso Ribeiro
2   Pediatric Neurology Department, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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Abstract

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232–25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

Keywords

centronuclear myopathy - mild phenotype - MTM1 gene - myotubularin - X-linked myotubular myopathy


Publication History

Received: 13 December 2020

Accepted: 09 March 2021

Article published online:
01 June 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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