Opportunistic genomic screening. Recommendations of the European Society of Human Genetics

Abstract

If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that ‘actionable’ genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings—so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.

Next-Generation Sequencing in Newborn Screening: A Review of Current State

“… Evans et al (2013) propose only a few of the genes from the ACMG list, for example, genes associated with Lynch syndrome, some highly penetrant cancer predisposition genes (e.g., APC , BRCA1 , BRCA2 , MYH , PTEN , and VHL ), genes associated with high risk for preventable vascular catastrophe (e.g., FBN1 , COL3A1 , and MYH11 ), and possibly genes for familial hypercholesterolemia ( Evans et al, 2013 ; Klančar et al, 2015 ; Groselj et al, 2018 ). The European Society of Human Genetics (ESHG) published recommendations on opportunistic genomic screening, where for minors they approve reporting of variants only for genes of conditions that are actionable early in life (such as MEN type 2A and hereditary arrhythmias such as long QT and Brugada syndrome) ( de Wert et al, 2020 ). Recently, Milko et al (2019) published a novel method to assess the potential actionability of genomic sequencing for certain conditions based on age.…”

“…A revised version of ACMG recommendations for reporting of secondary findings in clinical exome and genome sequencing is the first document that recommends reporting of information on select few actionable late-onset conditions in minors, with the explanation that this information could prove invaluable for the health of the parents ( Kalia et al, 2017 ). The ESHG published recommendations for opportunistic genomic screening in which they do not object to reporting of population pharmacogenomics (PGx) variants and variants leading to early onset actionable conditions ( de Wert et al, 2020 ). Despite professional guidelines deferring asymptomatic testing, carrier testing, or testing for late-onset diseases in minors, the public opinion may be in favor, as studies suggest ( Shkedi-Rafid et al, 2015 ; Waisbren et al, 2015 ).…”

“…Currently, all genetic testing requires informed consent to be obtained from the patient, parents, or legal guardian during a genetic counseling session performed by a medical geneticist or similar, before the testing ( ACMG Board of Directors, 2013 ). Many authors argue that if NBS will be based on genetic testing, some form of informed consent will be necessary ( Friedman, 2015 ; Howard et al, 2015 ; Berg et al, 2017 ; de Wert et al, 2020 ). Others propose solutions such as a panel of core conditions with proven benefits for the child for which no consent would be necessary ( Tarini and Goldenberg, 2012 ; Friedman, 2015 ).…”

“…The proposed benefits of testing a minor or in the case of NBS a newborn for an adult-onset disease would be a benefit of the parent or sibling who could become ill with the disease in question and could benefit from the NBS results of the child. The result could also enable parents to make informed decisions about future pregnancies ( McGuire et al, 2013 ; Wilfond et al, 2015 ; de Wert et al, 2020 ). Reporting of such variants would inevitably put enormous strain on the health system, with entire families requiring some form of management.…”

“…Wilson and Jungner proposed 10 criteria that should be met for the disease to be included in screening programs, which were later further revised ( Wilson et al, 1968 ; Andermann, 2008 ). Since the first idea of using NGS in the framework of NBS, several concerns have been raised, among them technical, medical, legal, economical, ethical, psychological, and sociological ( Friedman, 2015 ; Howard et al, 2015 ; Reinstein, 2015 ; Berg et al, 2017 ; Murray et al, 2018 ; Bouvier and Giguère, 2019 ; de Wert et al, 2020 ). In this review, we will discuss the recent advances in the use of NGS in the context of NBS, the remaining obstacles in its implementation in NBS, and the wider implications of its use in the NBS program.…”