Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Survival analysis of spinal muscular atrophy type I

  • Park, Hyun-Bin (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Lee, Soon-Min (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Lee, Jin-Sung (Department of Clinical Genetics, Yonsei University College of Medicine) ;
  • Park, Min-Soo (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Park, Kook-In (Department of Pediatrics, Yonsei University College of Medicine) ;
  • NamGung, Ran (Department of Pediatrics, Yonsei University College of Medicine) ;
  • Lee, Chul (Department of Pediatrics, Yonsei University College of Medicine)
  • Received : 2010.08.30
  • Accepted : 2010.10.19
  • Published : 2010.11.15
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Abstract

Purpose: The life expectancy of patients with spinal muscular atrophy (SMA) type I is generally considered to be less than 2 years. Recently, with the introduction of proactive treatments, a longer survival and an improved survival rate have been reported. In this study, we analyzed the natural courses and survival statistics of SMA type I patients and compared the clinical characteristics of the patients based on their survival periods. Methods: We reviewed the medical records of 14 pediatric patients diagnosed with SMA type I during a 9-year period. We examined the demographic and clinical characteristics of these patients, calculated their survival probabilities, and plotted survival curves as on the censoring date, January 1, 2010. We also compared the characteristics of the patients who died before the age of 24 months (early-death, ED group) and those who survived for 24 months or longer (long-survival, LS group). Results: The mean survival time was $22.8{\pm}2.0$ months. The survival probabilities at 6 months, 12 months, 18 months, 24 months, and 30 months were 92.9%, 92.9%, 76.0%, 76.0%, and 65.1%, respectively. Birth weight was the only factor that showed a statistically significant difference between the ED and LS groups ($P$=0.048). Conclusion: In this study, the survival probabilities at 2 years were far greater than expected. Because of the limited number of patients and information in this study, the contribution of improved supportive care on longer survival could not be clarified; this may be elucidated in larger cohort studies.

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References

  1. Cobben JM, Lemmink HH, Snoeck I, Barth PA, van der Lee JH, de Visser M. Survival in SMA type I: a prospective analysis of 34 consecutive cases. Neuromuscul Disord 2008;18:541-4. https://doi.org/10.1016/j.nmd.2008.05.008
  2. Wirth B, Herz M, Wetter A, Moskau S, Hahnen E, Rudnik-Schoneborn S, et al. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet 1999;64:1340-56. https://doi.org/10.1086/302369
  3. Pearn JH. The gene frequency of acute Werdnig-Hoffmann disease (SMA type 1). A total population survey in North-East England. J Med Genet 1973;10:260-5. https://doi.org/10.1136/jmg.10.3.260
  4. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet 1978;15:409-13. https://doi.org/10.1136/jmg.15.6.409
  5. Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics 2004;114:e548-53. https://doi.org/10.1542/peds.2004-0668
  6. Chung B, Wong V, Ip P. Prevalence of neuromuscular diseases in Chinese children: a study in southern China. J Child Neurol 2003;18:217-9. https://doi.org/10.1177/08830738030180030201
  7. Zerres K, Davies KE. 59th ENMC International Workshop: Spinal Muscular Atrophies: recent progress and revised diagnostic criteria 17-19 April 1998, Soestduinen, The Netherlands. Neuromuscul Disord 1999;9:272-8. https://doi.org/10.1016/S0960-8966(99)00016-4
  8. Munsat TL. Workshop report International SMA Collaboration. Neuromuscul Disord 1991;1:81. https://doi.org/10.1016/0960-8966(91)90052-T
  9. Borkowska J, Rudnik-Schoneborn S, Hausmanowa-Petrusewicz I, Zerres K. Early infantile form of spinal muscular atrophy (Werdnig-Hoffmann disease) with prolonged survival. Folia Neuropathol 2002;40:19-26.
  10. Nadeau A, D'Anjou G, Debray G, Robitaille Y, Simard LR, Vanasse M. A newborn with spinal muscular atrophy type 0 presenting with a clinicopathological picture suggestive of myotubular myopathy. J Child Neurol 2007;22:1301-4. https://doi.org/10.1177/0883073807307105
  11. Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat 2000;15:228-37. https://doi.org/10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9
  12. Oskoui M, Levy G, Garland CJ, Gray JM, O'Hagen J, De Vivo DC, et al. The changing natural history of spinal muscular atrophy type 1. Neurology 2007;69:1931-6. https://doi.org/10.1212/01.wnl.0000290830.40544.b9
  13. Byers RK, Banker BQ. Infantile muscular atrophy. Arch Neurol 1961;5:140-64. https://doi.org/10.1001/archneur.1961.00450140022003
  14. Ignatius J. The natural history of severe spinal muscular atrophy--further evidence for clinical subtypes. Neuromuscul Disord 1994;4:527-8. https://doi.org/10.1016/0960-8966(94)90094-9
  15. Thomas NH, Dubowitz V. The natural history of type I (severe) spinal muscular atrophy. Neuromuscul Disord 1994;4:497-502. https://doi.org/10.1016/0960-8966(94)90090-6
  16. Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 1995;52:518-23. https://doi.org/10.1001/archneur.1995.00540290108025
  17. Bach JR, Baird JS, Plosky D, Navado J, Weaver B. Spinal muscular atrophy type 1: management and outcomes. Pediatr Pulmonol 2002;34:16-22. https://doi.org/10.1002/ppul.10110
  18. Ioos C, Leclair-Richard D, Mrad S, Barois A, Estournet-Mathiaud B. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest 2004;126:831-7. https://doi.org/10.1378/chest.126.3.831
  19. Mannaa MM, Kalra M, Wong B, Cohen AP, Amin RS. Survival probabilities of patients with childhood spinal muscle atrophy. J Clin Neuromuscul Dis 2009;10:85-9. https://doi.org/10.1097/CND.0b013e318190310f
  20. Feldkotter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 2002;70:358-68. https://doi.org/10.1086/338627
  21. Wirth B, Brichta L, Schrank B, Lochmuller H, Blick S, Baasner A, et al. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Hum Genet 2006;119:422-8. https://doi.org/10.1007/s00439-006-0156-7
  22. Burghes AH. When is a deletion not a deletion? when it is converted. Am J Hum Genet 1997;61:9-15. https://doi.org/10.1086/513913
  23. Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, et al. Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy. Brain Dev 2009;31:42-5. https://doi.org/10.1016/j.braindev.2008.08.012
  24. Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 1999;8:1177-83. https://doi.org/10.1093/hmg/8.7.1177
  25. Lorson CL, Strasswimmer J, Yao JM, Baleja JD, Hahnen E, Wirth B, et al. SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 1998;19:63-6. https://doi.org/10.1038/ng0598-63
  26. Lorson CL, Androphy EJ. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet 2000;9:259-65. https://doi.org/10.1093/hmg/9.2.259
  27. Helmken C, Hofmann Y, Schoenen F, Oprea G, Raschke H, Rudnik-Schoneborn S, et al. Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1. Hum Genet 2003;114:11-21. https://doi.org/10.1007/s00439-003-1025-2

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