Family Genetic Risk Communication and Reverse Cascade Testing in the BabySeq Project

Genet Med. 2024 Dec 24:101350. doi: 10.1016/j.gim.2024.101350. Online ahead of print.

Abstract

Purpose: Genomic sequencing of newborns (NBSeq) can initiate disease surveillance and therapy for children, and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and had a risk for autosomal dominant disease identified.

Methods: We conducted semi-structured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely-pathogenic (P/LP) variant associated with an autosomal dominant (AD) childhood- and/or adult-onset disease returned. We utilized directed content analysis to derive themes.

Results: From 11 families, all first-degree relatives (n=32, 100%), 29 second-degree relatives (SDRs) (76%), and 26 third-degree relatives (TDRs) (43%) were informed of their risk. All parents (n=22, 69% of FDRs), four (11%) SDRs, and 1 (2%) TDR underwent cascade testing. Most parents preferred to handle risk communication themselves. Parents with positive cascade testing but no associated symptoms were less inclined to share findings with relatives, but highly motivated to share results if the variant's associated disease severity was high, as perceived with adult-onset conditions. One new subtheme, "family member traits," was identified and defined as a relative's propensity to anxiety/concern following risk communication, but did not diminish risk communication.

Conclusion: Findings can inform more effective notification and testing practices for families of newborns at risk for hereditary genetic conditions.

Keywords: Pediatrics; cascade testing; genetic risk communication; qualitative research.