Parents' perspectives of non-informative germline genetic testing in children with Juvenile Polyposis Syndrome

Juvenile Polyposis Syndrome (JPS) is a hereditary gastrointestinal polyposis condition characterized by the development of multiple juvenile-type hamartomatous polyps. Approximately half of individuals meeting clinical diagnostic criteria for JPS have an identifiable germline pathogenic variant in SMAD4 or BMPR1A, while the remaining individuals have non-informative genetic results. For pediatric cases, the proportion of children with an identifiable causative variant is likely much lower, with one study noting only 22% of pediatric patients having informative genetic testing. This qualitative study utilized surveys and interviews to explore the impact of non-informative germline genetic results for JPS on parents' understanding of their child's diagnosis and prognosis, as well as recurrence risk and familial screening uptake. Coding reliability thematic analysis of transcripts was completed through open inductive coding. Common parental experiences emerging from interviews with eight parents of seven children with JPS included emotional turmoil throughout the diagnostic process, prognostic unpredictability, and limited familial screening uptake. While the majority of participants (n = 7/8, 87.5%) correctly recalled their child's genetic testing results, those that did not receive genetic counseling (n = 3/8, 37.5%) described feeling confused and uninformed in the pre- and post-test setting. A majority of participants (n = 6/8, 75%) questioned the permanence, natural history, and severity of their child's JPS, while those with more time to cope felt greater clarity and less concern. Such parental perceptions were noted to be heavily influenced by differences in polyp burden over time, genetic testing results, and initial acceptance of the clinical diagnosis. The desire for a genetic diagnosis to increase clarity in their child's long-term management recommendations was noted by some participants (n = 2/8, 25%). Our findings highlight the importance of timely and clear education surrounding prognosis, early incorporation of a genetic counselor in the diagnostic process, and providing follow-up appointments to address misconceptions and resolve uncertainty.