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

Andreia Carvalho; Carmen Costa; Miguel Pinto; Ricardo Taipa; Ana Gonçalves; Márcia E. Oliveira; Sofia Ferreira; Joana Afonso Ribeiro

doi:10.1055/s-0041-1728745

Journal of Pediatric Genetics, Table of Contents

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

¹Neurology Department, Centro Hospitalar de Vila Nova de Gaia–Espinho, Portugal

,

Carmen Costa

²Pediatric Neurology Department, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

,

Miguel Pinto

³Neuropathology Unit, Hospital de Santo António - Centro Hospitalar Universitário do Porto, Porto, Portugal

,

Ricardo Taipa

³Neuropathology Unit, Hospital de Santo António - Centro Hospitalar Universitário do Porto, Porto, Portugal

⁴Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

,

Ana Gonçalves

⁴Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

⁵Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal

,

Márcia E. Oliveira

⁴Unit for Multidisciplinary Research In Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

⁵Molecular Genetics Unit, Centro de Genética Médica Dr. Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal

,

Sofia Ferreira

⁶Pulmonology Department, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

,

Joana Afonso Ribeiro

²Pediatric Neurology Department, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

› Author Affiliations

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

Full Text

References

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