Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening

J Pediatr. 2017 Nov:190:124-129.e1. doi: 10.1016/j.jpeds.2017.06.042. Epub 2017 Jul 12.


Objective: To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS).

Study design: We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample.

Results: Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2.

Conclusion: Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives.

Trial registration: NCT02123186.

Keywords: SMN1; newborn screening; real-time PCR; recombination; spinal muscular atrophy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Early Diagnosis
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Muscular Atrophy, Spinal / diagnosis*
  • Neonatal Screening / methods*
  • Pilot Projects
  • Real-Time Polymerase Chain Reaction / methods
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 2 Protein / genetics
  • Taiwan


  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein

Associated data