Pediatric reporting of genomic results study (PROGRESS): a mixed-methods, longitudinal, observational cohort study protocol to explore disclosure of actionable adult- and pediatric-onset genomic variants to minors and their parents

Abstract

Abstract Background Exome and genome sequencing are routinely used in clinical care and research. These technologies allow for the detection of pathogenic/likely pathogenic variants in clinically actionable genes. However, fueled in part by a lack of empirical evidence, controversy surrounds the provision of genetic results for adult-onset conditions to minors and their parents. We have designed a mixed-methods, longitudinal cohort study to collect empirical evidence to advance this debate. Methods Pediatric participants in the Geisinger MyCode® Community Health Initiative with available exome sequence data will have their variant files assessed for pathogenic/likely pathogenic variants in 60 genes designated as actionable by MyCode. Eight of these genes are associated with adult-onset conditions (Hereditary Breast and Ovarian Cancer Syndrome (HBOC), Lynch syndrome, MUTYH-associated polyposis, HFE-Associated Hereditary Hemochromatosis), while the remaining genes have pediatric onset. Prior to clinical confirmation of results, pediatric MyCode participants and their parents/legal guardians will be categorized into three study groups: 1) those with an apparent pathogenic/likely pathogenic variant in a gene associated with adult-onset disease, 2) those with an apparent pathogenic/likely pathogenic variant in a gene associated with pediatric-onset disease or with risk reduction interventions that begin in childhood, and 3) those with no apparent genomic result who are sex- and age-matched to Groups 1 and 2. Validated and published quantitative measures, semi-structured interviews, and a review of electronic health record data conducted over a 12-month period following disclosure of results will allow for comparison of psychosocial and behavioral outcomes among parents of minors (ages 0–17) and adolescents (ages 11–17) in each group. Discussion These data will provide guidance about the risks and benefits of informing minors and their family members about clinically actionable, adult-onset genetic conditions and, in turn, help to ensure these patients receive care that promotes physical and psychosocial health. Trial registration ClinicalTrials.gov Identifier: NCT03832985. Registered 6 February 2019