脊髓性肌肉萎縮症是一種體染色體隱性基因疾病,病患有兩個缺失或突變的SMN1基因,從父親及母親身上各遺傳一個4:

基因檢測是診斷SMA很重要的工具

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建議將SMN1基因缺失試驗作為疑似患有脊髓性肌肉萎縮症患者的第一診斷步驟。

可以經由聚合酶鍊式反應 (PCR) 測定來確定兩個染色體上的SMN1第七外顯子7是否缺失,此缺失在95%的SMA病患中發生。dPCR能夠可靠且準確地測量的SMN1SMN2基因數量(即0-6個拷貝數)。5,9

目前可選擇SMA新生兒篩檢。SMA的診斷時間至關重要。根據疾病的自然病史,早期診斷之後的早期介入可能有助於改善SMA患者的預後。15

References

1. Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155-165. 2. Kolb SJ, Kissel JT. Spinal muscular atrophy. Arch Neurol. 2011;68(8):979-984. 3. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133. 4. National Organization for Rare Diseases. Spinal muscular atrophy. 5. Prior TW. Spinal muscular atrophy: newborn and carrier screening. Obstet Gynecol Clin N Am. 2010;37(1):23-36. 6. Prior TW; Professional Practice Guidelines Committee. Carrier screening for spinal muscular atrophy. Genet Med. 2008;10(11):840-842. 7. Wang CH, Finkel RS, Bertini ES, et al; and Participants of the International Conference on SMA Standard of Care. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. 8. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis.2011;6:71. 9. Butchbach ME. Copy number variations in the survival motor neuron genes: implications for spinal muscular atrophy and other neurodegenerative diseases. Front Mol Biosci. 2016;3:7. 10. Pyatt RE, Mihal DC, Prior TW. Assessment of liquid microbead arrays for the screening of newborns for spinal muscular atrophy. Clin Chem. 2007;53(11):1879-1885. 11. Allele Diagnostics. Congenital hypotonia panel: DMPK repeat analysis, methlyation 15q, SMN1, uniparental disomy 14. https://www.allelediagnostics.com/services/tests/19/congenital-hypotonia-panel/. Accessed March 15, 2017. 12. EGL Genetics. Congenital hypotonia panel: spinal muscular atrophy deletions, Prader-Willi/Angelman syndrome methylation, myotonic dystrophy, and uniparental disomy 14. https://genetics.emory.edu/egl/tests/HY. Accessed March 15, 2017. 13. Saint Francis Center for Genetic Testing. Newborn hypotonia panel (DM1, PWS and SMA). https://www.saintfrancis.com/genetics/pages/laboratory-services/molecular-genetics/available-molecular-genetics-tests/newborn-hypotonia-panel.aspx. Accessed March 15, 2017. 14. NCBI. Congenital hypotonia panel. https://www.ncbi.nlm.nih.gov/gtr/tests/503277/. Updated June 15, 2016. Accessed March 15, 2017. 15. Rothwell E, Anderson RA, Swoboda KJ, Stark L, Botkin JR. Public attitudes regarding a pilot study of newborn screening for spinal muscular atrophy. Am J Med Genet A. 2013;161A(4):679-686. 16. Lin CS, Kalb SJ, Wei-Shi Y. Delay in diagnosis of spinal muscular atrophy: a systematic literature review. Pediatr Neurol. 2015;53:293-300. 17. Qian Y, McGraw S, Henne J, Jarecki J, Hobby K, Yeh WS. Understanding the experiences and needs of individuals with Spinal Muscular Atrophy and their parents: a qualitative study. BMC Neurol. 2015;15:217. doi:10.1186/s12883-015-0473-3. 18. Lawton SL, Hickerton C, Archibald AD, McClaren BJ, Metcalfe SA. A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy. Eur J Hum Genet. 2015;23(5):575-580. 19. RTI International. RTI Center on newborn screening, ethics, and disability studies. https://www.rti.org/impact/strengthening-newborn-screening-programs. Accessed March 15, 2017. 20. RTI to offer free genetic disease tests for North Carolina newborns. https://smanewstoday.com/2017/01/26/rti-international-to-offer-free-genetic-disease-testing-for-spinal-muscular-atrophy. Published January 26, 2017. Accessed March 15, 2017. 21. Cure SMA. Cure SMA launches newborn screening coalition. http://www.curesma.org/news/cure-sma-launches-newborn.html. Published February 10, 2017. Accessed March 15, 2017. 22. Leyenaar J, Camfield P, Camfield C. A schematic approach to hypotonia in infancy. Paediatr Child Health. 2005;10(7):397-400. 23. Peredo DE, Hannibal MC. The floppy infant: evaluation of hypotonia. Pediatr Rev. 2009;30(9):e66-e76. 24. Gowda V, Parr J, Jayawant S. Evaluation of the floppy infant. Paediatr Child Health. 2007;18:1. 25. Bodensteiner JB. The evaluation of the hypotonic infant. Semin Pediatr Neurol. 2008;15(1):10-20. 26. North KN. Clinical approach to the diagnosis of congenital myopathies. Semin Pediatr Neurol. 2011;18(4):216-220. 27. Van Toorn R. Clinical approach to the floppy child. CME: Your SA Journal of CPD. 2004;22(8):449-455. 28. McDonald CM. Clinical approach to the diagnostic evaluation of hereditary and acquired neuromuscular diseases. Phys Med Rehabil Clin N Am. 2012:23(3):495-563. 29. Darras BT, Royden Jones H Jr, Ryan MM, De Vivo DC, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd ed. London, UK: Elsevier; 2015. 30. Deenen JCW, Horlings CGC, Vershuuuren JJGM, et al. The epidemiology of neuromuscular disorders: a comprehensive overview of the literature. J Neuro Dis. 2015;73-85

診斷過程如何與父母/照護者的觀點不同?

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