Denise M Kay1, Colleen F Stevens2, April Parker2, Carlos A Saavedra-Matiz2, Virginia Sack2, Wendy K Chung3,4, Claudia A Chiriboga5, Kristin Engelstad5, Emma Laureta6, Osman Farooq7, Emma Ciafaloni8, Bo Hoon Lee8, Sohail Malek9, Simona Treidler10, Yaacov Anziska11, Leslie Delfiner12, Ai Sakonju13, Michele Caggana2. 1. Newborn Screening Program, Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, NY, USA. denise.kay@health.ny.gov. 2. Newborn Screening Program, Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, NY, USA. 3. Department of Pediatrics, Columbia University, New York, NY, USA. 4. Department of Medicine, Columbia University, New York, NY, USA. 5. Division of Child Neurology, Department of Neurology, Columbia University, New York, NY, USA. 6. Cohen Children's Medical Center, New Hyde Park, NY, USA. 7. Department of Neurology, Jacobs School of Medicine & Biomedical Sciences, University of Buffalo, Buffalo, NY, USA. 8. Department of Neurology, University of Rochester, Rochester, NY, USA. 9. Albany Medical Center, Albany, NY, USA. 10. Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA. 11. SUNY Downstate Medical Center, Brooklyn, NY, USA. 12. Montefiore Medical Center, Bronx, NY, USA. 13. SUNY Upstate Medical Center, Syracuse, NY, USA.
Abstract
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.
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.
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Authors: Katerina S Kucera; Jennifer L Taylor; Veronica R Robles; Kristin Clinard; Brooke Migliore; Beth Lincoln Boyea; Katherine C Okoniewski; Martin Duparc; Catherine W Rehder; Scott M Shone; Zheng Fan; Melissa Raspa; Holly L Peay; Anne C Wheeler; Cynthia M Powell; Donald B Bailey; Lisa M Gehtland Journal: Int J Neonatal Screen Date: 2021-03-21