Universal newborn genetic screening for pediatric cancer predisposition syndromes: model-based insights

Genet Med. 2021 Jul;23(7):1366-1371. doi: 10.1038/s41436-021-01124-x. Epub 2021 Mar 25.


Purpose: Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs.

Methods: We developed a simulation model to evaluate universal screening for a CPS panel. Cohorts of US newborns were simulated under universal screening versus usual care. Using data from clinical studies, ClinVar, and gnomAD, the presence of pathogenic/likely pathogenic (P/LP) variants in RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, and PHOX2B were assigned at birth. Newborns with identified variants underwent guideline surveillance. Survival benefit was modeled via reductions in advanced disease, cancer deaths, and treatment-related late mortality, assuming 100% adherence.

Results: Among 3.7 million newborns, under usual care, 1,803 developed a CPS malignancy before age 20. With universal screening, 13.3% were identified at birth as at-risk due to P/LP variant detection and underwent surveillance, resulting in a 53.5% decrease in cancer deaths in P/LP heterozygotes and a 7.8% decrease among the entire cohort before age 20. Given a test cost of $55, universal screening cost $244,860 per life-year gained; with a $20 test, the cost fell to $99,430 per life-year gained.

Conclusion: Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Child
  • Cost-Benefit Analysis
  • DEAD-box RNA Helicases
  • Early Detection of Cancer
  • Genetic Testing
  • Humans
  • Infant, Newborn
  • Mass Screening
  • Neonatal Screening*
  • Neoplasms* / diagnosis
  • Neoplasms* / genetics
  • Ribonuclease III
  • Syndrome
  • Young Adult


  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases