Spinal Muscular Atrophy: Genetic Screening

Spinal Muscular Atrophy: Genetic Screening

Spinal Muscular Atrophy (SMA) is an incurable, autosomal recessive inherited neuromuscular disease typified by progressive weakness and, in the most severe forms, death due to respiratory failure.1 SMA is the second most common congenital disease with an estimated worldwide incidence of approximately 1 in 10,000 live births.2 The reliability and diminishing cost of genetic testing makes widespread genetic screening for SMA technically feasible and cost-effective.3 The SMA genetic screening is a test for a homozygous deletion in exon 7 of the gene SMN1, the most common genetic finding associated with any form of SMA.4

Genetic screening for SMA can occur for several reasons:

  • Carrier screening for family planning purposes
  • Prenatal/preconception screening in a family with a history of SMA or known SMA carrier status
  • As part of a newborn screening program
  • Screening of an asymptomatic sibling of a patient with SMA

With respect to carrier screening in SMA, The American College of Obstetricians and Gynecologists (ACOG), among other medical organizations, currently recommends that, “All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for… spinal muscular atrophy….”5 Published research has confirmed that such pan-ethnic carrier screening is both useful for families and informative to the medical community.6,7

When a patient seeks advice in the setting of having a family history of SMA, ACOG advises that, in the absence of a confirmed test report for the affected individual or the results of carrier testing in the related parent, that SMA screening testing be offered to the low risk partner.8 The relative ease and widespread availability of SMA screening reinforces the importance awareness of ethical issues such as carrier status being revealed directly or indirectly to individuals who do not wish to know.9

SMA is not included in universal blood spot newborn screening performed on all newborns in the United States, but blood spot testing can identify SMN1 deletions.4,10 A pilot study of newborn screening for SMA in New York City had a 93% opt-in rate and identified one newborn with a severe genotype who subsequently had a successful early intervention.3 United States citizens desire universal newborn screening for SMA. Approximately 80% of respondents in a United States-based poll indicated a willingness to pay for newborn SMA screening even without a cure being available;11 similar results were obtained in a poll in the United Kingdom.12

Generally, genetic screening of asymptomatic siblings of patients with congenital diseases is discouraged on ethic grounds until the individual is mature enough to be involved in the choice to undergo testing.13 Carrier testing of siblings does occur despite recommendations against such testing with generally positive sentiments in families who receive results.14 The ethical argument against testing asymptomatic individuals at risk of having SMA were predicated on there being no intervention available to justify pre-symptomatic identification of a serious disease.15 With approved SMA treatments, this stance against early detection may be less defensible in public opinion.12


1. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet journal of rare diseases. 2011;6:71.

2. Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet journal of rare diseases. 2017;12(1):124.

3. Kraszewski JN, Kay DM, Stevens CF, et al. Pilot study of population-based newborn screening for spinal muscular atrophy in new york state. Genet Med. 2018;20(6):608-613.

4. Kato N, Sa’Adah N, Ar Rochmah M, et al. Sma screening system using dried blood spots on filter paper: Application of cop-pcr to the smn1 deletion test. Kobe J Med Sci. 2015;60(4):E78-85.

5. Committee opinion no. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40.

6. Sugarman EA, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20(1):27-32.

7. Wood SL, Brewer F, Ellison R, Biggio JR, Edwards RK. Prenatal carrier screening for spinal muscular atrophy. American journal of perinatology. 2016;33(12):1211-1217.

8. Committee opinion no. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.

9. Skirton H, Goldsmith L, Chitty LS. An easy test but a hard decision: Ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders. Eur J Hum Genet. 2015;23(8):1004-1009.

10. Taylor JL, Lee FK, Yazdanpanah GK, et al. Newborn blood spot screening test using multiplexed real-time pcr to simultaneously screen for spinal muscular atrophy and severe combined immunodeficiency. Clinical chemistry. 2015;61(2):412-419.

11. Lin PJ, Yeh WS, Neumann PJ. Willingness to pay for a newborn screening test for spinal muscular atrophy. Pediatr Neurol. 2017;66:69-75.

12. Boardman FK, Sadler C, Young PJ. Newborn genetic screening for spinal muscular atrophy in the uk: The views of the general population. Molecular genetics & genomic medicine. 2018;6(1):99-108.

13. Carre A, Empey C. Review of spinal muscular atrophy (sma) for prenatal and pediatric genetic counselors. Journal of genetic counseling. 2016;25(1):32-43.

14. Vears DF, Delany C, Massie J, Gillam L. Parents’ experiences with requesting carrier testing for their unaffected children. Genet Med. 2016;18(12):1199-1205.

15. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049.