Incidental Findings from Clinical Genome‐Wide Sequencing: A Review

Abstract

There are several unresolved challenges associated with the clinical application of genome-wide sequencing technologies. One of the most discussed issues is incidental findings (IF), which are defined as discoveries made as a result of genetic testing that are unrelated to the indication for the test. The discussion surrounding IF began in the context of research, which we have used to frame consideration of IF in the clinical context. There is growing consensus that analytically valid and medically actionable IF should be offered to patients, but whether and to what extent clinicians should disclose other kinds of IF is debated. While others have systematically reviewed the literature concerning genetic IF, previous reviews focus on ethical and research-related issues and do not consider the implications for the genetic counseling profession specifically. This review discusses the practical considerations, ethical concerns and genetic counseling issues related to IF, with a particular focus on clinical genome-wide sequencing. To date, the bulk of the literature with respect to IF in the clinical context consists of commentaries, reviews and case reports. There is a need for more empirical studies to provide a foundation for institutional protocols and evidence-based clinical practice standards.

Research participants in NGS studies want to know about incidental findings

“…17 In a review of IFs Lohn et al 17 have listed arguments against the disclosure of IFs as discussed by others. Abbreviations: A, disclosure of all IFs; B, disclosure of actionable variants; C, no disclosure of IFs; n, number of participants.…”

“…However, the authors conclude that non-disclosure may be unethical and that an intermediate disclosure policy between full and non-disclosure may be considered to guide disclosure decisions. 17 Most of these arguments are based on theoretical considerations and were not derived from studies of research participants. A systematic review on the ethical reflections on IFs was also conducted by Christenhusz et al 18 Considerations of WES in minors and the suggestion that parents could decide to learn about the risk for adult-onset diseases in their children have been raised as risks to an open future.…”

Compare and contrast: a cross-national study across UK, USA and Greek experts regarding return of incidental findings from clinical sequencing

“…While reflecting long-term practice, in today's world this raises the possibility of 'a potential conflict between patient autonomy and clinical paternalism'. 47 Autonomy was discussed by experts here and it appears that is perceived in different ways as has been suggested elsewhere. 48,49 Clinicians suggested that guidance, in any form it might take, should be topic specific but not too constraining, allowing clinicians and genetic counsellors to act according to their professional judgement when necessary.…”

Genome-Wide Sequencing for Prenatal Detection of Fetal Single-Gene Disorders

“…Guidelines need to be developed for the prenatal use of these new diagnostic modalities to address the circumstances in which they are best offered, how pre-and post-test counseling should proceed, what the most optimal ways are to obtain informed consent, which categories of results should be reported, and who decides on this within the informed consent process (Lohn et al 2013;Appelbaum et al 2014;Bui et al 2014;Holm et al 2014).…”