Identification of a Novel MTM1 Mutation Associated with X-Linked Myotubular Myopathy: Clinical and Molecular Insights for Prenatal Diagnosis

Given the clinical heterogeneity and generally poor prognosis of X-linked myotubular myopathy (XLMTM), the identification of prenatal indicators and relevant medical history is imperative. However, studies specifically addressing the prenatal manifestations of this condition remain limited. Therefore, we investigated a case of XLMTM characterized by persistent polyhydramnios and conducted a comprehensive literature review. A neonate diagnosed with XLMTM was identified at the Fujian Provincial Maternity and Children’s Hospital, Fuzhou, China. Genetic analysis, including whole exome sequencing (WES) and Sanger sequencing, was performed on the infant and his parents. Pathogenic variants were classified following American College of Medical Genetics and Genomics criteria. A literature review examined prenatal features of polyhydramnios in male infants with XLMTM. The mother experienced persistent idiopathic polyhydramnios and underwent amniotic fluid reduction and prenatal diagnosis. Despite normal fetal karyotyping and single nucleotide polymorphism-array findings, the neonate, born at 36 weeks, had severe respiratory failure and died 1.5 h post-resuscitation. WES identified a pathogenic hemizygous frameshift mutation within exon 10 of MTM1 (c.968_969delinsT, p.K323Mfs*2). A literature review revealed phenotypic variability in XLMTM, with single-nucleotide variations being the most common mutation type. The novel MTM1 mutation (c.968_969delinsT, p.K323Mfs*2) caused XLMTM in this case. The prenatal characteristics exhibited by the mother, including persistent amniotic fluid and reduced fetal movement, highlight the need for WES in high-risk pregnancies, offering critical insights for prenatal diagnosis and genetic counselling.