Abstract
BackgroundIncidental and secondary findings (IFs and SFs) are subject to ongoing discussion as potential consequences of clinical exome sequencing (ES). International policy documents vary on the reporting of these findings. Discussion points include the practice of unintentionally identified IFs versus deliberately pursued SFs, patient opt-out possibilities and the spectrum of reportable findings. The heterogeneity of advice permits a non-standardised disclosure but research is lacking on actual reporting practices. Therefore, this study assessed national reporting practices for IFs and SFs in clinical ES and the underlying professional perspectives.MethodsA qualitative focus group study has been undertaken, including professionals from Belgian centres for medical genetics (CMGs). Data were analysed thematically.ResultsAll Belgian CMGs participated in this study. Data analysis resulted in six main themes, including one regarding the reporting criteria used for IFs. All CMGs currently use ES-based panel testing. They have limited experience with IFs in clinical ES and are cautious about the pursuit of SFs. Two main reporting criteria for IFs were referred to by all CMGs: the clinical significance of the IF (including pathogenicity and medical actionability) and patient-related factors (including the patient’s preference to know and patient characteristics). The consensus over the importance of these criteria contrasted with their challenging interpretation and application. Points of concern included IFs’ pathogenicity in non-symptomatic persons, IFs concerning variants of uncertain significance, the requirement and definition of medical actionability and patient opt-out possibilities. Finally, reporting decisions were guided by the interaction between the clinical significance of the IF and patient characteristics. This interaction questions the possible disclosure of findings with context-dependent and personal utility, such as IFs concerning a carrier status. To evaluate the IF’s final relevance, a professional and case-by-case deliberation was considered essential.ConclusionsThe challenging application of reporting criteria for IFs results in diversified practices and policy perspectives within Belgian CMGs. This echoes international concerns and may have consequences for effective policy recommendations.
Highlights
Incidental and secondary findings (IFs and SFs) are subject to ongoing discussion as potential consequences of clinical exome sequencing (ES)
When considering the reporting of Incidental findings (IFs), Belgian centres for medical genetics (CMGs) referred to two major criteria: the clinical significance of the IF and patient-related factors
Clinical significance of the IF Currently, Belgian CMGs do not analyse the full exome in clinical ES and mainly use exome-based panels, hitherto resulting in a rather limited experience with IFs in clinical ES
Summary
Incidental and secondary findings (IFs and SFs) are subject to ongoing discussion as potential consequences of clinical exome sequencing (ES). According to the ACMG, screening for (likely) pathogenic variants in the diagnostically unrelated gene panel should occur in every case of clinical exome and genome sequencing, as a realisation of the professional duty to avoid harm [2, 3, 10, 13] This opportunistic screening has been criticised and the American Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) notes how it might entail additional health risks, overwhelm patients with (ambivalent) information and stimulate a trend of medicalisation [5]. They advocate a strictly necessary and proportional application of ES and, if possible, (exome or genome-based) targeted panel testing, which only analyses a subset of known disease-associated genes and minimises the possibility of diagnostically unrelated IFs [1, 4, 7]
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