Disclosures: Clarisse San Juan, MD: No financial relationships or conflicts of interest

Case Diagnosis: X-linked myotubular myopathy manifested from infancy in a female

Case Description: A 5-year-old African American female presented for developmental delay and generalized weakness. Delayed milestones were noted in infancy, with sitting at 9 months, walking, pulling to stand, and speaking monosyllables at 18 months. She had difficulty walking, climbing and getting up from a sitting position, but no issues with fine motor tasks. At age 6, she needed help getting into a car, toileting, bathing and dressing. She frequently tripped and fell while running. At age 9, she had difficulties running due to dyspnea and weakness — pulmonary function tests showed a reduced forced vital capacity. She had delayed speech despite speech therapy since 18 months. Physical exam showed left-sided facial droop with hypoplasia, proximal asymmetrical weakness, absent reflexes, hypotonia, wide-based waddling gait and positive Gower sign. She has a younger sister who is asymptomatic.

Setting: ClinicAssessment/

Results: MRI brain at another facility was normal. Labs showed a normal TSH, CPK and aldolase. She had a negative genetic test at another facility at 18 months of age (2012). In 2017, limb-girdle muscular dystrophy panel (EGL Genetics) was negative. In 2018, right deltoid muscle biopsy was non-diagnostic, showing chronic myopathic features, with myofiber atrophy, internalized nuclei and endomysial fibrosis, however, staining for dystrophy-associated proteins was negative. Invitae neuromuscular panel identified a pathogenic variant in MTM1, associated with X-linked centronuclear myopathy, with gross deletion of the genomic region encompassing the full coding sequence of the MTM1 gene.

Discussion: X-linked myotubular myopathy almost exclusively manifests in males. The pathogenic MTM1 gene manifested most likely due to X-inactivation of the normal allele causing predominant expression of the pathogenic allele.

Conclusion: X-inactivation is the likely determinant of X-linked myotubular myopathy progression and severity and X-inactivation studies to determine the degree of skewing may elucidate its association to disease severity.

Level of Evidence: Level V

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PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/x-linked-recessive-myotubular-myopathy-in-a-female-child-a-case-report/