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Spinal muscular atrophy is an autosomal recessive genetic disease in which an individual inherits 2 deleted or mutated SMN1 genes—1 from each parent4:

The American College of Medical Genetics and Genomics (ACMG) recommends that because SMA is found in all populations, carrier screening should be offered to couples of all races and ethnicities. The ACMG suggests that the testing be performed either before conception or early in pregnancy to allow carriers to make informed reproductive choices.6

Molecular genetic testing is an important tool in the diagnosis of spinal muscular atrophy7,8

The SMN1 gene deletion test is recommended as the first diagnostic step for a patient suspected to have spinal muscular atrophy.

The deletion status can be tested by using polymerase chain reaction (PCR) to determine if both copies of SMN1 exon 7 are absent, which occurs in 95% of affected individuals. PCR can reliably and accurately measure SMN1 and SMN2 copy numbers over a wide range (ie, 0-6 copies).5,9

Although newborn screening is not yet standard practice, time to diagnosis is critical. Based on the natural history of the disease, earlier diagnosis leading to earlier intervention may help improve outcomes for individuals with SMA.15


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. 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. Accessed March 15, 2017. 13. Saint Francis Center for Genetic Testing. Newborn hypotonia panel (DM1, PWS and SMA). Accessed March 15, 2017. 14. NCBI. Congenital hypotonia panel. 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. Accessed March 15, 2017. 20. RTI to offer free genetic disease tests for North Carolina newborns. Published January 26, 2017. Accessed March 15, 2017. 21. Cure SMA. Cure SMA launches newborn screening coalition. 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

How might the diagnostic process differ from the perspective of a parent/caregiver?

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