X-Linked Centronuclear Myopathy

ABSTRACT

We report the cases of two male preterm newborns with X-linked centronuclear myopathy (CNM). This is the most severe type of CNM. Each of them presented with generalized hypotonia, weakness, difficulty in swallowing, and respiratory distress at birth. Physical examination of both newborns revealed long thin face, high-arched palate, mild bilateral ptosis, frog-leg posture, and absence of deep tendon reflex. Diagnosis of the disease was made according to fetal history, family history, muscle histopathology, electron microscopy, and genetic analysis. Subdural hemorrhage of brain and subcapsular hematoma of the liver were found at autopsy of Case 1. The results of molecular analysis of Case 2 and his family favored the diagnosis of X-linked CNM. Molecular studies can be easily performed with only minute amount of DNA of patients, and may help the clinician to predict which patients may be at the risk for medical complications.

KEYWORDS

X-linked centronuclear myopathy - histopathology - molecular analysis

REFERENCES

• 1 Spiro A J, Shy G M, Gonatas N K. Myotubular myopathy.  Arch Neurol . 1966;  14 1-14
• 2 De Angelis S M, Palmucci L, Leone M, Doriguzzi C. Centronuclear myopathy: clinical, morphological and genetic characters: a review of 288 cases.  J Neurol Sci . 1991;  103 2-9
• 3 Barth P G, Van Wijngaarden K G, Bethlem J. X-linked myotubular myopathy with fatal neonatal asphyxia.  Neurology . 1975;  25 531-536
• 4 Kunkel L M, Smith K D, Boyer S H. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants.  Proc Natl Acad Sci U S A . 1977;  74 1245-1249
• 5 Li P, Thompson J N, Wang X, Song L. Analysis of common mutations and associated haplotypes in Chinese patients with glucose-6-phosphate dehydrogenase deficiency.  Biochem Mol Biol Int . 1998;  46 1135-1143
• 6 Vincent M C, Guiraud-Chaumeil C, Laporte J, Manouvrier-Hanu S, Mandel J L. Extensive germinal mosaicism in a family with X linked myotubular myopathy simulates genetic heterogeneity.  J Med Genet . 1998;  35 241-243
• 7 Sher J M, Rimalovski A B, Athanassiades T J, Aronson S M. Familial centronuclear myopathy: a clinical and pathological study.  Neurology . 1967;  17 727-742
• 8 Goebel H H, Anderson J R. Structural congenital myopathies (excluding nemaline myopathy, myotubular myopathy and desminopathies): 56th European Neuromuscular Centre (ENMC) sponsored International Workshop, December 12-14, 1997, Naarden, The Netherlands.  Neuromuscul Disord . 1999;  9 50-57
• 9 Tsai C H, Huang W S, Tsai F J, Lee C C, Chen S S. X-linked recessive myotubular myopathy proven by muscle biopsy.  J Formos Med Assoc . 1996;  95 153-156
• 10 Goebel H H. Congenital myopathies.  Semin Pediatr Neurol . 1996;  3 152-161
• 11 Moosa A, Dawood A A. Centronuclear myopathy in black African children: report of 4 cases.  Neuropediatrics . 1987;  18 213-217
• 12 Collins J E, Collins A, Radford M R, Weller R O. Perinatal diagnosis of myotubular (centronuclear) myopathy: a case report.  Clin Neuropathol . 1983;  2 79-82
• 13 Bruyland M, Liebaers I, Sacre L, Vandeplas Y, De Meirleir L, Martin J J. Neonatal myotubular myopathy with a probable X-linked inheritance: observations on a new family with a review of the literature.  J Neurol . 1984;  231 220-222
• 14 Sarnat H B, Roth S I, Jimenez J F. Neonatal myotubular myopathy: neuropathy and failure of postnatal maturation of fetal muscle.  Can J Neurol Sci . 1981;  8 313-320
• 15 Keppen L D, Husain M M, Woody R C. X-linked myotubular myopathy: intrafamilial variability and normal muscle biopsy in a heterozygous female.  Clin Genet . 1987;  32 95-99
• 16 Hu L J, Laporte J, Kress W, Dahl N. Prenatal diagnosis of X-linked myotubular myopathy: strategies using new and tightly linked DNA markers.  Prenat Diagn . 1996;  16 231-237
• 17 Myung K, Chen C, Kolodner R D. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae.  Nature . 2001;  411 1073-1076
• 18 Laporte J, Hu L J, Kretz C. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.  Nat Genet . 1996;  13 175-182
• 19 Herman G E, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy.  J Pediatr . 1999;  134 206-214