Implications for paediatric biobanks of professional guidelines on genetic testing in children

The discovery of the Huntingtin gene in 1993 meant that accurate predictive or pre-symptomatic genetic testing for Huntington's disease was possible.

This single-gene adult-onset neurodegenerative condition is dominant and highly penetrant. Meaning that if a person has the gene variant then they will develop the condition. There would also be a 50 percent chance of any of their children inheriting the altered gene. At the time of the identification of the gene there was no effective treatment available, although today there is active research interest with the development of treatment trials.

The possibility of such predictive or pre-symptomatic genetic testing led to consideration of issues in offering testing to a child or young person. This 'new' type of testing and in particular valid consent formed the basis of developing professional guidelines on testing children and young people for later onset inherited conditions.

The original guidelines in the UK (1994) and also internationally, recommended that predictive or pre-symptomatic genetic testing was relevant in childhood if it offered the opportunity for medical intervention. However, predictive testing for adult-onset disorders should not be performed until the child was an adult. The main argument being this enabled the child to give informed consent and preserved their future autonomy.

Of course, a genetic test can offer timely and important benefits, for example establishing a diagnosis or determining treatment options. Professional concerns are primarily related to genetic analysis that gives information about future illnesses either in the medium or the long term. These potential illnesses are not evident at the time of any testing.

With the growth of biobanks that contain genomic data, more and more people are having their whole genome, or parts of their genome sequenced and analysed for research purposes.

The recent announcement that a paediatric biobank will be launched to obtain and analyse genomic data from children and young people in the UK, by the UK's National Institute of Health Research's undoubtedly meets an important research need. The information materials from the DNA, Children + Young People's Health Resource (D-CYPHR) are clear that at the current time they do not intend returning individual genetic information to participants. However, the consent is broad and it is possible that future studies will include investigation of particular genetic variants and risk of future disease.

Research analysis is different from performing a genetic test on a child for medical reasons. Genomic analysis and genetic testing in children in the clinical world has been an active area for discussion over the last 30 years and the subject of many professional guidelines. Original guidelines were cautious but as the possibilities for genetic testing have increased, they have been revised and updated. The latest guidance for clinical practice on genetic testing in childhood was published in November 2022 by the Royal College of Physicians.

Although D-CYPHR is a paediatric genomic biobank, it is relevant to consider the issues raised by these guidelines.

As the most recent UK Guidelines above acknowledge, professional concerns about conditions that present in childhood or testing for carrier status have lessened. Discussions regarding a condition in childhood where testing could alleviate familial concerns, may focus on when is the best time to test and how to involve the child. Discussions about carrier testing which will be relevant when the child themselves comes to have children may also take into account aspects such as when should the child be involved in decisions, how is the result communicated and kept so that the information can be used when it is relevant. For some conditions being a carrier may also mean that you develop some aspects of the disorder. These conversations can be complex.

The principles underpinning decision making regarding genetic testing in childhood are clearly set out in current guidelines. The first principle is that the child's best interest is paramount and this includes identifying the child's autonomy rights and including them in the discussion. All medical testing (and also participation in research) should be authorised by appropriate consent. In clinical practice, a child is assumed to have capacity to give consent to treatment, which includes testing from the age of 16. Before that, parents or formal guardians have a legal responsibility to give consent for a child under the age of 16 unless the child is deemed 'Gillick' competent, in the UK.

The guidelines support that generally it is in the best interest of the child to delay a predictive test for an adult-onset disorder with no implications during childhood until the child themselves can be involved in the decision and give valid consent.

How does this predominantly clinical landscape relate to the new D-CYPHR?

Consideration of the child's best interest and understanding their rights to autonomy underpin children's participation in research. Although the intention may be not to return individual results from genetic research, there is a growing literature exploring this. The majority of the published literature is from the USA and indicates interest from adult participants in receiving such results, and more cautious interest from researchers in returning them.

In opinion pieces and ethical analyses regarding child participants, the basic principles in professional guidelines that results of adult-onset disorders should generally not be returned are accepted. However also in line with professional guidelines, discussions regarding treatable or actionable conditions presenting in childhood are more nuanced. Again principles of involving child participants in decision making was recommended when this was visited in 2013 in Nature.  

A major issue for long-term resources such as the proposed D-CYPHR biobank is how to maintain the valid consent status of the participant recruited as a child. Recommended practice supported by the Health Research Authority in the UK and professional guidelines is for the child to give consent for continued participation in a longitudinal cohort at the age of 16. Re-consenting all participants is a significant challenge for researchers. An additional issue is that in some research projects, not all child participants will attain capacity and be able to give their consent in their own right. This is discussed from the perspective of participants in Nature, by the chair of the participant panel of the 100,000 Genomes Project, whose child has a rare genetic disorder diagnosed through the Project.

Although not the subject of this commentary, it is also important to consider that valid consent to participation in any research study underpins policies and principles of how data access and potential use by other researchers across different jurisdictions is managed and facilitated. This is currently an area of great interest as evidenced in the Goldacre Review, as there is a desire to facilitate such data access and use for research. Of course, this should not impact on the confidentiality, privacy and also expectations of research participants. For all biobanks, it is necessary to work with participants and other stakeholders including researchers, clinicians, policymakers and others to develop processes that comply with the commitments that have been made and also with accepted good practice. This is a significant operational challenge to maintain at scale and needs to be planned for at the beginning of the project.

Professional guidelines on genetic testing in children at first glance might not seem to be relevant to a resource that is not planning to return individual results, such as the D-CYPHR project. However, there may be specific circumstances, for example a desire to return results with significant health implications where treatment is available, where this policy changes in the future. Awareness of guidelines and good practice in this area will aid in navigating these difficult decisions.

The research value of such paediatric biobanks is contingent on participants with appropriate consent continuing to allow their data and samples to be accessed and used by a wide range of researchers.

Maintaining valid consent requires both engagement and involvement of participants in decisions being made and, in addition, building a resource where assurance that only data from individuals who have given current appropriate consent is accessible. This will go towards protecting the current and future autonomy of those individuals who became participants during childhood, and who allow access to their data and samples by researchers, possibly across their whole lifespan and beyond.