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Whole Genome Sequencing at Birth: What Should Be Looked For? What Should Be Fed Back?

22 November 2021
By Dr Jess Buxton
Dr Jess Buxton, Senior Lecturer in Medical Genetics, Kingston University
Appeared in BioNews 1122

Advances in human genetics have continued apace in recent years, thanks to ever-cheaper and faster genome sequencing technologies. The UK's 100,000 Genomes Project explored how best to use genomic data to improve diagnosis and effective interventions for people affected by rare genetic conditions and cancer. Following on from this, a new ethics-approved research pilot study embedded in the NHS will next explore whether and how to offer whole genome sequencing (WGS) to newborn babies.

The Newborn Genomes Programme will examine the practical, ethical and societal questions raised by the possibility of expanding the current newborn screening programme in the UK, which currently tests for just nine conditions. Could this list be greatly expanded to detect a wide range of rare childhood-onset genetic disorders? If so, which conditions and variants should be screened for, and what information should be fed back to parents? Should the list be limited to conditions for which an existing effective therapy already exists, or should it also include conditions for which promising treatments are on the horizon? These questions were addressed at 'Whole Genome Sequencing at Birth: What Should Be Looked For? What Should Be Fed Back?', an event produced by the Progress Educational Trust (the charity that publishes BioNews) in partnership with Genomics England.

The event, chaired by PET's director Sarah Norcross, started with an overview of the Newborn Genomes Programme from Dr Richard Scott, chief medical officer at Genomics England and consultant in clinical genetics at Great Ormond Street Hospital for Children. He set the scene by emphasising that the planned work will be 'human-centred, ethical and translatable', and will explore three main areas: early diagnosis and care for rare genetic conditions; enabling research and new treatments for NHS patients; and the potential benefits, risks and other implications of having a lifetime genomic record.

On the question of which conditions should be tested for in newborns, Dr Scott first spoke of the public dialogue commissioned by Genomics England and the UK National Screening Committee (NSC), which found broad support for the use of WGS in newborn screening (see BioNews 1103). But he also pointed out that the views of families affected by rare genetic conditions may be very different to those held by the 'general' public. Providing a tantalising glimpse of what may one day be possible, he cited a recently created compendium of genetic disorders for which some form of treatment exists. When the compendium was launched a year ago, it contained entries for 633 of the thousands of diseases caused by pathogenic genetic variants.

The next speaker, Dr Charles Steward, provided both a professional and personal perspective. He is lead for Patient Advocacy and Engagement at Congenica, and also the parent of two children with severe neurological disorders who participated in the 100,000 Genomes Project. Due to his family circumstances, he contributed to the debate through a prerecorded interview with Norcross (the interview is available to watch on BioNews). Dr Steward spoke of the expert knowledge and valuable insights that families affected by rare diseases can often bring to those who care for them, in some cases even diagnosing their own child's condition following their own research into the symptoms.

Both of Dr Steward's children are affected by the same type of cerebral palsy, but the underlying cause is currently unknown. When asked by Norcross if the list of conditions screened for in newborns should be updated to add those with promising new therapies, Dr Steward said it should, and provided a very practical explanation for his answer: what better way to encourage companies to develop new treatments for such conditions than to include them in a screening panel?

Professor Frances Flinter, an emeritus professor of clinical genetics at King's College London and trustee at PET, spoke next. She considered both the pros and cons of expanding the newborn screening programme through the use of WGS data. For conditions in which detection would provide 'actionable results', the advantages would include early diagnosis and intervention. Another potential benefit would be the establishment and expansion of large genetic databases that would speed up research into new treatments. However, Professor Flinter also emphasised that the list of conditions screened for needs to be driven by clinical need and the most appropriate test currently available. For example, some metabolic conditions are more accurately diagnosed using techniques such as mass spectrometry, rather than WGS.

One of the potential downsides of WGS screening at birth highlighted by Professor Flinter is that the NHS currently has insufficient capacity to counsel parents about the implications of any findings. She also raised the issues of whether and how inconclusive findings should be communicated; the risk of worry caused by false positive results; and the risk of harm caused by false negative results. In addition to these questions (which could apply to the communication of genetic test results at any age), she said there is also a risk of damaging the parents' relationships with their infant, if they embark on a diagnostic journey during these crucial early days.

The last speaker was Dr Emma Baple, a consultant in clinical genetics at the Royal Devon and Exeter Hospital and a member of the Newborn Genomes Programme's NHS Steering Group. She started by emphasising the guiding principles of the WGS pilot study, particularly its co-development with patients and public groups, and stressed the need to balance what should be done with what can be done. She went on to describe in greater detail how the conditions and genetic variants screened for will be chosen, in light of both their clinical utility and their clinical validity.

Dr Baple then spoke of the inevitable grey areas that may arise when these principles are put into practice. Returning to the compendium of genetic conditions that could potentially be treated, she showed that some of these conditions arise in childhood and are substantially reversible if treated early. However, there are also conditions that meet only one of these criteria, or that meet neither of these criteria, because there is currently no effective treatment and/or because symptoms occur later in life. Such conditions pose greater challenges.

The four well-balanced and very informative expert presentations were followed by a panel discussion of questions submitted by the audience. These questions focused on a wide range of issues including ways of ensuring patient involvement in the pilot through effective public engagement, technical developments to improve WGS diagnostic rates, the challenges posed by uncertain results (particularly in asymptomatic individuals), and legal and ethical challenges including a child's right 'not to know'.

PET is grateful to Genomics England and its Newborn Genomes Programme for supporting this event. Our next online events will be:

22 November 2021 - by BioNews 
A conversation between Sarah Norcross (director of the Progress Educational Trust) and Dr Charles Steward (lead for patient advocacy and engagement at Congenica, and parent of two children with severe neurological disorders)...
15 November 2021 - by Joseph Hawkins 
Whole genome sequencing of NHS patients with rare diseases can provide diagnoses that could lead to more personalised care or treatment and potentially save the NHS money, a study has shown...
15 November 2021 - by Christina Burke 
Outcomes for child cancer patients could be dramatically improved by sequencing their genomes, a study has shown...
8 November 2021 - by Dr Yvonne Collins 
Currently, only nine conditions are screened for in the UK, which is fewer than many other high-income countries. Although many patient groups advocate for new conditions to be added to the list, this has not happened...
31 August 2021 - by Jen Willows 
Offering healthy people genetic screening could provide clinically important information in over 15 percent of cases...
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