title: Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation.
abstract: X-linked myotubular myopathy is a severe congenital myopathy in males, caused by mutations in the myotubularin (MTM1) gene on chromosome Xq28. In heterozygous carriers of MTM1 mutations, clinical symptoms are usually absent or only mild. We report a 6-year-old girl presenting at birth with marked hypotonia and associated feeding and respiratory difficulties. A muscle biopsy performed at 5 months suggested a diagnosis of myotubular myopathy. On examination at 6 years she had marked facial weakness with bilateral ptosis and external ophthalmoplegia, severe axial and proximal weakness and a mild scoliosis. Muscle magnetic resonance imaging showed a distinctive pattern of muscle involvement. Molecular genetic investigation of the MTM1 gene identified a heterozygous mutation in exon 12. X-inactivation studies in lymphocytes showed an extremely skewed pattern (97:3). This case emphasizes that investigation of the MTM1 gene and X-inactivation studies are indicated in isolated females with histopathological and clinical findings suggestive of myotubular myopathy.
authors.affiliation: Department of Paediatrics, Dubowitz Neuromuscular Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jungbluth
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: A
authors.initials: A
authors.lastname: Buj-Bello
authors.forename: M
authors.initials: M
authors.lastname: Kristiansen
authors.forename: K H
authors.initials: KH
authors.lastname: Ørstavik
authors.forename: A
authors.initials: A
authors.lastname: Kelsey
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: C
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D002648:Child; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D009123:Muscle Hypotonia; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000473:pathology; D009886:Ophthalmoplegia; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012729:Sex Chromosome Aberrations
chemical_list: D017027:Protein Tyrosine Phosphatases