Conclusions (2), Conclusions | Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews

Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews · Conclusions

Conclusions (2)

CC BY 4.0 · National Institute for Health and Care Research · approximately 1 min read

A traditional approach to systematic reviewing for WGS of newborns is unfeasible, and the review does not reveal a new way to evaluate WGS for newborn screening in a single mechanism. There are two reasons for this: (1) there was insufficient evidence on each condition to allow a conventional UK NSC assessment and (2) the variations in penetrance, natural history, test accuracy and effectiveness of treatments mean that an aggregate is not informative. Our review highlights the main evidence gaps and informs the direction of future research efforts.

We propose a series of possible research approaches undertaken in large joined-up collaborations to produce the evidence that is needed for policy advisors before an evaluation of WGS is feasible. This may include a co-ordinated international approach to collecting penetrance data. This could be followed by a staged approach of evaluation considering only pathogenic variants with a very high penetrance for screening.

Attribution. Karoline Freeman; Jacqueline Dinnes; Bethany Shinkins; Corinna Clark; Inès Kander; Katie Scandrett et al. (2025). Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews. National Institute for Health and Care Research. Copyright © 2025 Freeman et al. Licensed under CC BY 4.0. NCBI Bookshelf NBK619683. CC BY 4.0. Original source ↗. Text reproduced from the Bookshelf XML without changing wording; figures, images and supplements are not reproduced.