When Owen Everitt reached his first birthday, his parents, Sarah and Rob, were already wondering if there might be a problem with his development.
“He hadn’t really started to crawl or talk, he wasn’t starting to babble as many babies usually do between nine and twelve months, and he wasn’t sitting up, so that’s when I began to have concerns,” says Sarah.
Although they went to see several paediatricians, none were able to diagnose Owen with any specific condition.
“We spent many hours in hospital waiting rooms, being referred from one department to another, but all the tests, some of which were quite invasive, came back negative every time,” says 44-year old Sarah.
Owen was having difficulty eating and often had constipation or diarrhoea, and doctors prescribed medication for anaemia and then growth hormone treatment, but these only had a limited benefit.
When Owen was five, they were referred to a consultant at St Mary’s Hospital in Paddington, west London, who suggested they take part in the 100,000 Genomes Project, a national initiative to sequence and study the role our genes play in health and disease, run by Genomics England. Finally, they found some answers. Owen’s genome was sequenced, and in 2018, at the age of six, he was diagnosed with THRA-related congenital hypothyroidism, a rare genetic condition where the thyroid gland fails to work properly, affecting growth and development.
Owen was only the sixth person in the UK, and the 30th in the world, to be diagnosed with the gene disorder, which is not inherited, but due to a spontaneous mutation in a person’s DNA.
Though his condition is rare, studies have shown there are at least 7,000 single gene disorders, most of which develop during early childhood. Many families face years of tests and uncertainty before receiving a diagnosis, as symptoms often develop slowly, and by the time a diagnosis is confirmed the condition may have progressed considerably.
Owen now takes a daily pill called levothyroxine, which replaces a hormone normally produced by the thyroid, and is doing well at school and at home. “In his early years, he didn’t have any energy to walk or talk and would just fall asleep during the middle of day, but now he’s full of energy and I can’t keep up with him,” says Sarah. He goes for regular six-monthly checks at Addenbrooke’s Hospital in Cambridge.
Following the success of the 100,000 Genomes project, British scientists have now launched another ambitious initiative – sequencing another 100,000 babies. It began in September this year, and aims to sequence the genomes of 100,000 babies over two years and gather evidence to assess whether the service should be rolled out across the country. The researchers say that if rare diseases such as Owen’s can be picked up earlier, many children could be offered existing treatments much sooner, improving their long-term health prospects.
The project, funded with ₤105m from the Department of Health and Social Care (DHSC), will be the first time that genome sequencing has been offered to parents with healthy babies in the NHS. Parents having babies at 14 NHS hospitals across the country will be invited to have their baby’s genome sequenced – to improve future testing and treatment of rare conditions in the future.
Genomics England, which was set up by the DHSC, and is now run commercially, claims it is the largest study of its kind in the world, and, if successful, it could lead to wider genetic testing being offered routinely in future.
Dr Richard Scott, chief medical officer at Genomics England and a consultant in clinical genetics at Great Ormond Street Hospital for Children, says that around 3,000 children with genetic disorders are born every year in the UK, and many could benefit from the study. “We want to look for conditions that are ‘actionable’ – that is, [in children] that can be given existing treatments, so it’s like shining a spotlight on a certain range of conditions where we can make an intervention now,” says Dr Scott.
Currently, the heel prick test given to all newborns by the NHS tests for nine rare but serious conditions including cystic fibrosis, congenital hypothyroidism, phenylketonuria, classical galactosaemia and maple syrup urine disease (MSUD). The study, says Dr Scott, will “hugely expand the range of conditions for which we can screen”.
“We’re having a continuing dialogue with the public about which diseases we should include in screening and there is still a complex set of questions which need to be addressed. Although our public consultation shows great support for the use of screening in newborns, the technology is moving forwards very quickly, and we need to ensure that parents who will take part in the project are fully aware of all the implications.
“We also need to look at the workforce requirements, such as specialist genetics nurses, of offering this service to parents of newborns, in terms of providing expertise and support from the NHS.”
“Parents-to-be at participating hospitals are being informed about the study during pregnancy,” explains Dr Amanda Pichini, clinical director of Genomics England. “This includes informing them about the study’s key aims, namely, to evaluate the use of genome sequencing to screen newborn babies for more than 200 rare genetic conditions, which usually appear as symptoms in the first few years of life. We explain that these can be improved if caught early, and treated by the NHS.
“As part of the study, we will ask all parents’ permission to securely store their baby’s genome and health information, which can be accessed for approved research anonymously, without researchers knowing babies’ identities. This research will help us to learn more about the causes of genetic conditions and improve how we test for and treat them in the future.
“Another goal is to look at the possible risks and benefits of storing an individual’s genome over their lifetime. This includes the potential for future opportunities to look for other health conditions or to make a diagnosis when someone develops symptoms of a genetic condition.”
Lucy White’s nine year-old son Joshua Curtis has early juvenile metachromatic leukodystrophy (MLD), one of the conditions being tested for in the study. She says: “When Josh was born, we had concerns about his mobility, his hand-eye co-ordination and difficulties he had with swallowing. It took us two years, after many tests and hospital appointments, to get a diagnosis because his condition was so rare. With earlier diagnosis, Josh could have benefited from transformational gene therapy on the NHS, which would have been life-changing.
“Sadly, it was too late for Josh to receive treatment as his symptoms had progressed too far and he has lost all of the abilities he once had. As a family, the diagnosis of MLD has had a massive impact. I hope that this study will help other families and children access the treatment they need sooner.”
However, some genetic specialists take a more cautious view of the ethics around routine screening for newborns. Frances Flinter, emeritus professor of clinical genetics at Guy’s and St Thomas’ Hospital in London, and a member of the Nuffield Bioethics Council, says that screening in this way is “a step into the unknown” and parents could be unnecessarily worried by the tests.
“Studies have revealed some surprising results, where apparently healthy adults may have genetic alterations [mutations] that we would expect to cause serious disease, and yet they remain healthy. We do not understand why this is, but, by implication, not all babies with apparently harmful genetic alterations will go on to develop a genetic disease,” she explains.
“The aim of giving an early, and in some cases, pre-symptomatic diagnosis of a wider range of conditions, will undoubtedly benefit some children and may even save lives. But it’s important that parents who give consent for their newborn babies to become enrolled into this research project also understand the risks,” says Professor Flinter.
“Ensuring that parents can make informed choices about whether they want their baby to have this kind of testing, and what happens to the genomic data collected, will be vital. Pharmaceutical companies will certainly be interested in acquiring it.”
Professor Flinter points out that many NHS staff, such as midwives, would need to be trained in genetic counselling to support parents who choose the newborn screening, and that this could increase demands on the NHS, where children’s services are already under pressure, as parents seek treatment for a child who is asymptomatic and may never develop a particular disease.
For Owen and his family, the screening has proven life-changing. He is now very active at school, doing some sports, and developing normally. “It feels like we’ve won the lottery,” says Sarah. “I’d certainly recommend that other parents take advantage of the screening service if they are offered it.”
