My son stopped developing – it took six years to figure out why

By the time Owen Everitt reached his first birthday, his parents Sarah and Rob were already wondering whether there might be a problem with his development.

“He hadn’t really started crawling or talking yet, he wasn’t starting to babble like many babies between nine and 12 months old do, and he wasn’t sitting up anymore, so I started to worry says Sarah.

Although they visited several pediatricians, none were able to diagnose Owen with a 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 had difficulty eating and often suffered from constipation or diarrhea. Doctors prescribed anti-anemia medication followed by growth hormone treatment, but these had limited effect.

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 of our genes in health and disease Genomics England. Eventually 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 disorder in which the thyroid gland does not function properly, affecting growth and development.

Owen was only the sixth person in the UK and the 30th worldwide to be diagnosed with the genetic disorder, which is not inherited but results from a spontaneous mutation in a person’s DNA.

Although its condition is rare, studies have shown that there are at least 7,000 individual gene disorders, most of which develop in early childhood. Many families face years of testing and uncertainty before diagnosis because symptoms often develop slowly and the condition may have already progressed significantly by the time the diagnosis is confirmed.

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 had no energy to walk or talk and would just fall asleep in the middle of the day, but now he’s full of energy and I can’t keep up with him,” says Sarah. He has regular six-monthly check-ups at Addenbrooke’s Hospital in Cambridge.

Following the success of the 100,000 Genomes Project, British scientists have now launched another ambitious initiative – sequencing an additional 100,000 babies. It began in September this year and aims to sequence the genomes of 100,000 babies over two years and collect evidence to assess whether the service should be rolled out across the country. The researchers say that if rare diseases like Owen’s disease could be detected earlier, many children could be offered existing treatments much earlier, improving their long-term health prospects.

The ₤105m project, funded by the Department of Health and Social Care (DHSC), will be the first time genome sequencing has been offered to parents of healthy babies on the NHS. Parents having babies at 14 NHS hospitals across the country are being invited to have their baby’s genome sequenced – to improve future testing and treatment for rare diseases.

Genomics England, set up by the DHSC and now running commercially, claims it is the largest study of its kind in the world and, if successful, could lead to more comprehensive genetic testing being offered routinely in the future.

Dr. Richard Scott, chief medical officer at Genomics England and consultant in clinical genetics at Great Ormond Street Hospital for Children, says around 3,000 children are born with genetic disorders in the UK every year and many could benefit from the study. “We want to look for conditions that are ‘actionable’ – that is, (in children) that can be treated with existing treatments. “So it’s like putting a spotlight on a particular spectrum of conditions that we can now intervene on,” says Dr Scott.

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The NHS is currently testing all newborns for nine rare but serious conditions using the heel prick test, including cystic fibrosis, congenital hypothyroidism, phenylketonuria, classical galactosemia and maple syrup urine disease (MSUD). The study, says Dr. Scott, will “greatly expand the range of conditions we can look for.”

“We have an ongoing dialogue with the public about which diseases we should include in screening and there are still a number of complex questions that need to be resolved. Although our public consultation shows strong support for the use of newborn screening, technology is advancing very quickly and we need to ensure that parents taking part in the project are fully aware of all the implications.

“We also need to look at workforce requirements, such as specialist genetics nurses, to provide this service to parents of newborns, with a view to providing expertise and support on the NHS.”

“Expectant parents in participating hospitals will be informed about the study during their pregnancy,” explains Dr. Amanda Pichini, clinical director of Genomics England. “This includes informing them about the main objectives of the study, namely to evaluate the use of genome sequencing to screen newborns for more than 200 rare genetic diseases that usually present as symptoms in the first years of life.” We explain that this improves can be prevented if detected early and treated by the NHS.

“As part of the study, we will ask all parents for permission to securely store their baby’s genome and health information so that it can be accessed anonymously for approved research purposes, without researchers knowing the babies’ identities. This research will help us learn more about the causes of genetic diseases and improve the way we test and treat them in the future.

“Another goal is to examine the potential risks and benefits of storing an individual’s genome over their lifetime. This includes the potential for future opportunities to screen for other health conditions or make a diagnosis if someone develops symptoms of a genetic disease.”

Lucy White’s nine-year-old son Joshua Curtis suffers from 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, hand-eye coordination and difficulty swallowing. It took two years before we received a diagnosis after many tests and hospital appointments because his condition was so rare. Had he been diagnosed earlier, Josh could have benefited from transformative gene therapy on the NHS, which would have been life-changing.

“Unfortunately it was too late for Josh to seek treatment as his symptoms had progressed too far and he had lost all the skills he once had. The MLD diagnosis had a huge impact on the family. I hope this study will help other families and children get quicker access to the treatment they need.”

However, some geneticists are more cautious about the ethics surrounding routine newborn screening. 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 screening in this way is “a step into the unknown” and parents could be unnecessarily alarmed by the tests.

“Studies have shown some surprising results in which seemingly healthy adults can have genetic changes (mutations) that we would expect to cause serious disease and still remain healthy.” We don’t understand why this is, but from this “It follows that not all babies with seemingly harmful genetic changes will go on to develop a genetic disease,” she explains.

“The aim of providing early and in some cases presymptomatic diagnosis of a wider range of conditions will undoubtedly benefit some children and potentially even save lives.” But it is important that parents agree to have their newborns included in this research project “, also understand the risks,” says Professor Flinter.

“It will be crucial to ensure that parents can make an informed decision about whether their baby wants to have these types of tests and what happens to the genomic data collected.” Pharmaceutical companies will certainly be interested in adopting it.”

Professor Flinter points out that many NHS staff, such as midwives, would need to be trained in genetic counseling to support parents who choose newborn screening and that this could increase the demands on the NHS as parents where childcare is already under pressure Seek treatment for a child who is asymptomatic and may never develop a particular disease.

For Owen and his family, the screening proved life-changing. He is now very active at school, plays sports and is developing normally. “It feels like we won the lottery,” says Sarah. “I would definitely recommend other parents take up the screening service if it is offered to them.”