Parents, their children, whole exome sequencing and unsolicited findings: growing towards the child's future autonomy.

Aad Tibben,Eva Brilstra,Ineke Bolt,Nine Knoers,Wybo Dondorp,Candice Cornelis,Marieke Van Summeren

doi:10.1038/s41431-020-00794-6

Abstract

In a previous study we found that parents of children with developmental delay (DD) favoured acceptance of unsolicited findings (UFs) for medically actionable conditions in childhood, but that preferences diverged for UFs with no medical actionability, or only in adulthood, and regarding carrier status. Sometimes the child's future autonomy formed a reason for withholding UFs for the present, despite an unfavourable prognosis concerning the child's cognitive capabilities. This might be different for children undergoing whole exome sequencing (WES) for reasons other than DD and who are expected to exert future autonomy. This is the focus of the current study. We conducted nine qualitative, semi-structured interviews with parents of children, ages <1-15, after consenting to WES, but prior to feedback of results, and with three adolescent children. Several parents wished to receive any information that might in whatever way be relevant to the health and well-being of their child, and to a lesser extent wished the inclusion of information about non-actionable disorders and information concerning carrier status of autosomal recessive disorders. Although parents understood the rationale behind the centre's UFs disclosure policy, they also felt that they needed this information in order to be able to exert their parental responsibility and take good care of a child still dependent on them. Parents reason from their notion of parental responsibility but are also inclined to take adolescent children's preferences seriously and acknowledge the child's incipient autonomy as a ground for granting an increasing degree of self-determination on the road to adulthood.

Highlights

Compared with traditional methods, whole exome sequencing (WES) enables rapid mapping of DNA for reaching a diagnosis in cases of suspected, yet unclarified, genetic disorders
Given the relevance of culture-related family dynamics, similar studies need to be conducted with families from other ethnic backgrounds. In this exploratory study of the preferences and considerations of parents of children undergoing WES for reasons other than developmental delay, we have observed a strongly shared view that any information that might in whatever way be relevant to the health and well-being of their child in the course of its further life, should be available to them to enable them to exercise their parental responsibility
Parents appreciated the restrictions imposed by the policy of the institution, they felt that information about non-actionable disorders, and information concerning carrier status of autosomal recessive disorders and later-onset conditions, should be an option in case parents felt they needed the information in order to care for their child and to protect their child’s best interests

Summary

Introduction

Whole exome sequencing (WES) enables rapid mapping of DNA for reaching a diagnosis in cases of suspected, yet unclarified, genetic disorders. WES provides the opportunity to achieve a diagnosis [1, 2], often does not end a diagnostic odyssey [3]. Even though WES may reveal a finding, these findings often have no significance for the course of treatment. Apart from diagnostic findings, WES has the potential for generating additional findings, known as incidental findings, beyond those related to the indication for sequencing [4]. In this paper we have adopted the European Society of Human Genetics’ preferred term: unsolicited findings (UFs) [5]. WES’s potential for revealing unsolicited findings raises the issue of how UFs should be disclosed/withheld, and under what conditions. How should UFs be presented during pre-test counselling so that informed consent is safeguarded [4, 6,7,8]?

Objectives

Methods

Results

Discussion

Conclusion