Broadening the scope on Whole-Exome Sequencing (WES) in pediatric practice: decision-making in parents of (expected-) competent children

Whole exome sequencing (WES) maps the protein coding regions of the genome and can be used to unravel suspected, yet unclarified, genetic disorders. WES may reveal to diagnosis but may also lead to incidental findings (IF). Such findings can be either medically actionable, either immediately or only in the future, or non-actionable, may have reproductive significance and consequences for family members. Besides IF, WES may also lead to variants of unknown/unclear significance (VUS) that may only become interpretable with future scientific insights. WES raises ethical questions regarding the disclosure of incidental findings and an optimal informed consent procedure. In our previous ZonMw project (ZonMw 731010005, completed in October 2015), we conducted an empirical-ethical study of parents’ views and experiences regarding the informed consent procedure for WES for their children. However, as WES was first introduced into clinical pediatric practice at UMC Utrecht (UMCU) for the indications intellectual disability with/without multiple congenital abnormalities, these children were not expected to develop into competent adults, meaning that their future autonomy rights were, in so far, not at stake. The UMCU has now expanded the range of indications for WES beyond conditions involving intellectual disability. The use of WES in this context raises ethical questions that differ from the context of incompetent children. Since the child cannot decide upon the testing, the parents are asked to give their proxy consent. Competent adults may have the right to remain ignorant of genetic information regarding themselves but do parents have ‘the right not to know’ with regard to certain IF that may results from WES about their child? Is it morally acceptable to give parents the option of indicating that they do not want to be informed about IF, with no further qualification or condition? Should parents be informed if the condition is treatable but not yet in childhood? Do parents have the right to know in case of a severe, untreatable late onset disorder? Or does such a right to know infringe upon the right to an open future of the child? Furthermore, is there a difference being a parent of a very young child versus being parent of an older child? When can children be qualified as competent to play a role in the decision-making process? In other words, what may parents decide for their children who are expected to become competent? Finally, are parents capable to understand and oversee the complex information and consequences of WES? And what are the practical limitations or concerns that need to be taken into account when devising concrete informed consent procedures? This research proposal is a follow-up study regarding parental experiences of (expected-)competent (EC) children, the scope and limits of parental autonomy and parental en professional responsibility, a right (not) to know, and children’s interests and (future) autonomy. This project focuses on how the possibility of future autonomous decision-making of the child further complicates decision-making process for diagnostic WES, as investigated in the previous project. An empirical study using focus groups into the views and experiences of parents of EC children will inform the ethical analysis. Together with the results of the previous study, both projects will provide guidelines how a responsible informed consent policy for WES in pediatrics including counseling en re-contact procedures should designed.