Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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X-linked recessive myotubular myopathy with MTM1 mutations

  • Han, Young-Mi (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Kwon, Kyoung-Ah (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Lee, Yun-Jin (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Nam, Sang-Ook (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Park, Kyung-Hee (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Byun, Shin-Yun (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Clinic and Laboratory, Asan Medical Center Children's Hospital) ;
  • Yoo, Han-Wook (Medical Genetics Clinic and Laboratory, Asan Medical Center Children's Hospital)
  • Received : 2011.09.07
  • Accepted : 2012.08.02
  • Published : 2013.03.15
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Abstract

X-linked recessive myotubular myopathy (XLMTM) is a severe congenital muscle disorder caused by mutations in the MTM1 gene and characterized by severe hypotonia and generalized muscle weakness in affected males. It is generally a fatal disorder during the neonatal period and early infancy. The diagnosis is based on typical histopathological findings on muscle biopsy, combined with suggestive clinical features. We experienced a case of a newborn who required intubation and ventilator care because of profound hypotonia and respiratory difficulty. The preliminary diagnosis at the time of request for retrieval was hypoxic ischemic encephalopathy, but the infant was clinically reevaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size and centrally located nuclei in nearly all the fibers. We detected an MTM1 gene mutation of c.1261-1C>A in the intron 10 region, and diagnosed the neonate with myotubular myopathy. The same mutation was detected in his mother.

Keywords

References

  1. Laporte J, Hu LJ, Kretz C, Mandel JL, Kioschis P, Coy JF, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet 1996;13:175-82. https://doi.org/10.1038/ng0696-175
  2. Wallgren-Pettersson C, Jungbluth H. Congenital myopathies. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR, editors. Emery and Rimoin's principles and practice of medical genetics. 5th ed. London: Churchill Livingstone, 2007:2971-3.
  3. Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol 2005;64:555-64. https://doi.org/10.1097/01.jnen.0000171653.17213.2e
  4. Beggs AH, Bohm J, Snead E, Kozlowski M, Maurer M, Minor K, et al. MTM1 mutation associated with X-linked myotubular myopathy in Labrador Retrievers. Proc Natl Acad Sci U S A 2010; 107:14697-702. https://doi.org/10.1073/pnas.1003677107
  5. McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M, et al. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord 2002;12:939-46. https://doi.org/10.1016/S0960-8966(02)00153-0
  6. Tanner SM, Schneider V, Thomas NS, Clarke A, Lazarou L, Liechti-Gallati S. Characterization of 34 novel and six known MTM1 gene mutations in 47 unrelated X-linked myotubular myopathy patients. Neuromuscul Disord 1999;9:41-9. https://doi.org/10.1016/S0960-8966(98)00090-X
  7. Laporte J, Biancalana V, Tanner SM, Kress W, Schneider V, Wallgren-Pettersson C, et al. MTM1 mutations in X-linked myotubular myopathy. Hum Mutat 2000;15:393-409. https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<393::AID-HUMU1>3.0.CO;2-R
  8. Chi JG. Myotubular myopathy: a case report. Korean J Pathol 1986;20:328-31.
  9. Hwang H, Kwon HJ, Chai JH, Kim KJ, Hwang YS. Familial myotubular myopathy occurred in a sibling. J Korean Child Neurol Soc 2001;9:425-9.
  10. Jeon JH, Namgung R, Park MS, Park KI, Lee C, Lee JS, et al. X- linked myotubular myopathy in a family with two infant siblings: a case with MTM1 mutation. Yonsei Med J 2011;52:547-50. https://doi.org/10.3349/ymj.2011.52.3.547
  11. Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis 2008;3:26. https://doi.org/10.1186/1750-1172-3-26
  12. Barth PG, Dubowitz V. X-linked myotubular myopathy: a long-term follow-up study. Eur J Paediatr Neurol 1998;2:49-56. https://doi.org/10.1016/1090-3798(98)01004-9
  13. Herman GE, Kopacz K, Zhao W, Mills PL, Metzenberg A, Das S. Characterization of mutations in fifty North American patients with X-linked myotubular myopathy. Hum Mutat 2002;19:114-21. https://doi.org/10.1002/humu.10033
  14. de Gouyon BM, Zhao W, Laporte J, Mandel JL, Metzenberg A, Herman GE. Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy. Hum Mol Genet 1997;6:1499-504. https://doi.org/10.1093/hmg/6.9.1499
  15. Laporte J, Guiraud-Chaumeil C, Vincent MC, Mandel JL, Tanner SM, Liechti-Gallati S, et al. Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center. Hum Mol Genet 1997;6:1505-11. https://doi.org/10.1093/hmg/6.9.1505
  16. Bijarnia S, Puri RD, Jain M, Kler N, Roy S, Urtizberea JA, et al. Mutation studies in X-linked myotubular myopathy in three Indian families. Indian J Pediatr 2010;77:431-3. https://doi.org/10.1007/s12098-010-0057-6
  17. Fujimura-Kiyono C, Racz GZ, Nishino I. Myotubular/centronuclear myopathy and central core disease. Neurol India 2008;56: 325-32. https://doi.org/10.4103/0028-3886.43451
  18. Herman GE, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy. J Pediatr 1999;134:206-14. https://doi.org/10.1016/S0022-3476(99)70417-8
  19. Yu S, Manson J, White S, Bourne A, Waddy H, Davis M, et al. X-linked myotubular myopathy in a family with three adult survivors. Clin Genet 2003;64:148-52. https://doi.org/10.1034/j.1399-0004.2003.00118.x

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