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

Denise M. Kay, Colleen F. Stevens, April Parker, Carlos A. Saavedra-Matiz, Virginia Sack, Wendy K. Chung, Claudia A. Chiriboga, Kristin Engelstad, Emma Laureta, Osman Farooq, Emma Ciafaloni, Bo Hoon Lee, Sohail Malek, Simona Treidler, Yaacov Anziska, Leslie Delfiner, Ai Sakonju, Michele Caggana

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1296-1302
Number of pages7
JournalGenetics in Medicine
Issue number8
StatePublished - Aug 1 2020


  • Recommended Uniform Screening Panel (RUSP)
  • SMN1
  • carrier screening
  • newborn screening (NBS)
  • spinal muscular atrophy (SMA)

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'Implementation of population-based newborn screening reveals low incidence of spinal muscular atrophy'. Together they form a unique fingerprint.

Cite this