Implementation of population-based newborn screening reveals low incidence of spinal muscular atrophy

Genet Med. 2020 Aug;22(8):1296-1302. doi: 10.1038/s41436-020-0824-3. Epub 2020 May 18.


Purpose: Spinal muscular atrophy (SMA) was added to the Recommended Uniform Screening Panel (RUSP) in July 2018, following FDA approval of the first effective SMA treatment, and demonstration of feasibility of high-throughput newborn screening using a primary molecular assay. SMA newborn screening was implemented in New York State (NYS) on 1 October 2018.

Methods: Screening was conducted using DNA extracted from dried blood spots with a multiplex real-time quantitative polymerase chain reaction (qPCR) assay targeting the recurrent SMN1 exon 7 gene deletion.

Results: During the first year, 225,093 infants were tested. Eight screened positive, were referred for follow-up, and confirmed to be homozygous for the deletion. Infants with two or three copies of the SMN2 gene, predicting more severe, earlier-onset SMA, were treated with antisense oligonucleotide and/or gene therapy. One infant with ≥4 copies SMN2 also received gene therapy.

Conclusion: Newborn screening permits presymptomatic SMA diagnosis, when treatment initiation is most beneficial. At 1 in 28,137 (95% confidence interval [CI]: 1 in 14,259 to 55,525), the NYS SMA incidence is 2.6- to 4.7-fold lower than expected. The low SMA incidence is likely attributable to imprecise and biased estimates, coupled with increased awareness, access to and uptake of carrier screening, genetic counseling, cascade testing, prenatal diagnosis, and advanced reproductive technologies.

Keywords: Recommended Uniform Screening Panel (RUSP); SMN1; carrier screening; newborn screening (NBS); spinal muscular atrophy (SMA).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Homozygote
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Muscular Atrophy, Spinal* / diagnosis
  • Muscular Atrophy, Spinal* / epidemiology
  • Muscular Atrophy, Spinal* / genetics
  • Neonatal Screening*
  • New York
  • Pregnancy
  • Survival of Motor Neuron 1 Protein / genetics


  • Survival of Motor Neuron 1 Protein