The full spectrum of ethical issues in pediatric genome-wide sequencing: a systematic qualitative review

Abstract

Background The use of genome-wide sequencing in pediatric medicine and research is growing exponentially. While this has many potential benefits, the normative and empirical literature has highlighted various ethical issues. There have not been, however, any systematic reviews of these issues. The aim of this systematic review is to determine systematically the spectrum of ethical issues that is raised for stakeholders in in pediatric genome-wide sequencing. Methods A systematic review in PubMed and Google Books (publications in English or German between 2004 and 2021) was conducted. Further references were identified via reference screening. Data were analyzed and synthesized using qualitative content analysis. Ethical issues were defined as arising when a relevant normative principle is not adequately considered or when two principles come into conflict. Results Our literature search retrieved 3175 publications of which 143 were included in the analysis. Together these mentioned 106 ethical issues in pediatric genome-wide sequencing, categorized into five themes along the pediatric genome-wide sequencing lifecycle. Most ethical issues identified in relation to genome-wide sequencing typically reflect ethical issues that arise in general genetic testing, but they are often amplified by the increased quantity of data obtained, and associated uncertainties. The most frequently discussed ethical aspects concern the issue of unsolicited findings. Conclusion Concentration of the debate on unsolicited findings risks overlooking other ethical challenges. An overarching difficulty presents the terminological confusion: both with regard to both the test procedure/ the scope of analysis, as well as with the topic of unsolicited findings. It is important that the genetics and ethics communities together with other medical professions involved work jointly on specific case related guidelines to grant the maximum benefit for the care of the children, while preventing patient harm and disproportionate overload of clinicians and the healthcare system by the wealth of available options and economic incentives to increase testing.

Hope, but never expect? Comparing parents' pre‐ and post‐disclosure attitudes toward return of results from diagnostic exome sequencing for their child

“…The reasoning they offered for this was that they had had high expectations that a diagnosis, or at least a VUS, would be achieved with WES. The finding that disappointment occurs, or even increases, when persons have heightened or unrealistic expectations about the type of result they will receive, is consistent with insights of other empirical studies and points to acknowledging expectation management as part of the informed consent process (Bos & Bunnik, 2022;Donohue et al, 2021;Eichinger et al, 2023;Peter et al, 2022;Wynn et al, 2018). However, our results show that this observation should be built upon further, since parents who adopted a hopeful stance about what WES might offer them reported being ultimately more satisfied with the whole sequencing experience than the couple in our study who expected a certain outcome or answers from WES and thus reported being disappointed.…”

“…A simple reminder that hopes are inherently different from expectations may help protect against overly optimistic assumptions and disappointment. This finding can be added to insights generated on expectation management found elsewhere that have stressed the need to mitigate against false hopes and unrealistic expectations through various strategies, such as encouraging parents to take some extra time to reflect on their choices in more detail before actually obtaining written consent for sequencing (Bos & Bunnik, 2022;Eichinger et al, 2023;Gore et al, 2019;Wynn et al, 2018).…”

Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center

“…Notably, in Turkey, the formal establishment of genetic counseling as a profession is yet to be realized, resulting in clinical geneticists assuming the responsibility of guiding patients through both preand post-test phases. This task, which can be particularly challenging, has been referred to as a "nightmare" in other countries (Eichinger et al, 2023).…”

Experiences of pediatric cancer patients (age 12–18 years) with extensive germline sequencing for cancer predisposition: a qualitative study

“…Testing children for cancer predisposition is a topic of ongoing ethical debate [ 5 ]. This debate encompasses various issues, including what information should be provided during the consent process, what appropriate timing of consent would be, how children should be involved in decision-making, and whether re-consent is desirable when children reach the age of majority.…”