Major study diagnoses thousands of people with rare genetic diseases
The study - led by the team from the University of Exeter - has been carried out thanks to volunteers like Jessica Fisher's son, Mungo from St Austell
Around the UK, thousands of people now know the cause of their rare genetic diseases thanks to the work of a major research study - based right here in the South West.
Around 5,500 people in the country now know the genetic cause of their condition thanks to the study led by the University of Exeter - and it's now hoped their results will help to improve the rate of diagnosis across the globe.
Here in the UK and Ireland, more than 13,500 families took part in the Deciphering Developmental Disorders (DDD) study, a collaboration between the NHS and the Wellcome Sanger Institute funded by Wellcome and the Department of Health and Social Care, and supported by the National Institute for Health and Care Research.
All the families had children with a severe developmental disorder, which was undiagnosed despite prior testing through their national health service.
The diagnoses were in over 800 different genes, and around three-quarters of the conditions were caused by spontaneous mutations not inherited from either parent.
Lead author Caroline Wright, Professor of Genomic Medicine at the University of Exeter, said: “Getting the right diagnosis is absolutely critical for families with rare conditions, which collectively affect around 1 in 17 people. Most of these conditions are genetic and can be diagnosed using the same genomic sequencing technology.
"The families in our study were desperate for answers, which can make a huge difference to clinical management and quality of life. We worked with hundreds of clinicians and scientists, as well as thousands of patients to try to find those answers. By sharing our findings, many more families in the future should get answers faster.”
Senior co-author Matthew Hurles, incoming Director of the Wellcome Sanger Institute and Honorary Professor of Human Genetics and Genomics at the University of Cambridge, said responsible data sharing was critical for making the diagnoses.
He added: “Undiagnosed patients with rare genetic diseases have the most to lose if they are not given an opportunity to participate in research and if their data are kept in silos. Many of these diagnoses were only made possible through combining data across all diagnostic centres in the UK and Ireland.
"For some diagnoses, it was only through sharing data with international colleagues that it was possible to make a diagnosis. As these genomic technologies move into routine healthcare, ensuring that undiagnosed patients can still benefit from research on their data will remain incredibly important.”
The study was all about helping to diagnose people more swiftly.
Now, a similar approach to diagnosing individuals with rare diseases is being used in the NHS by the Genomic Medicine Service, the Scottish Genomics Laboratories Network Whole Exome Sequencing Service, and the Rapid Genome Sequencing Service for acutely unwell children with a likely monogenic disorder.
Health Minister, Will Quince, said: “We’re creating the most advanced genomic healthcare system in the world and this study is yet another step forward to revolutionising care for NHS patients.
“Using cutting edge, high-tech methods such as this offers the potential to better understand and more accurately diagnose rare genetic conditions so children can access treatment faster and potentially limit the impact of the disease on their life.”
How diagnosis impacts families
Behind every diagnosis is a story of a family impacted by the effect of the genetic disorder - whether or not the cause of that disease has yet been medically discovered.
Following a diagnosis of an ultra-rare condition is then a world of support, and a community of other with similar experiences, which can then be shared - one of those stories from the South West is Jessica Fisher from St Austell, and her son Mungo.
Before her son's diagnosis, she initially felt it had all come too late. Mungo’s condition, called Turnpenny-Fry syndrome, was discovered in 2015 through the Deciphering Developmental Disorders study, in which he was a participant.
But he was already 18 – Jessica, from St Austell in Cornwall, had been through years of uncertainty, not knowing how her son’s development would unfold.
However, she took solace in being connected with another family recently diagnosed through the study, and forming a Facebook support group. Now, the group has connected around 36 families from across the world making it an invaluable community for those who are newly diagnosed.
Jessica said: “When I first saw a picture emailed to me of the other family’s child it was really emotional.
“We’d always looked around for children who might look like Mungo – and here was a child in Australia who could have been his sibling. For a few months it was just us two families, but then it slowly started to grow.
"We now have families from countries including America, Brazil, Croatia, Indonesia… it’s devastating to learn that your child has a rare genetic disorder, but getting the diagnosis has been key to bringing us together. The families are so appreciative to learn from our group, and being part of it does make us feel less isolated.
"Nowadays, we take it for granted if there are children out there with developmental disorders that there is a diagnosis or a label, and we never imagine that there are so many out there who have a condition that could be undiscovered, unknown, or very rare. It can be hugely isolating.
"Now my son is 26, and if we didn't have a diagnosis, I would still be in the dark today. To be with people who have exactly the same needs as him is such a relief - and it's wonderful to have built such a community."
Turnpenny-Fry syndrome is caused by extremely rare changes in a gene called PCGF2. The disorder causes learning difficulties, impaired growth, and distinctive facial features that include a large forehead and sparse hair. Other common issues include feeding problems, severe constipation, and a range of potential issues in the brain, heart, circulation system and bones.
For Dasha Brogden, the support group has been a lifeline. Her daughter, Sofia, now nearly three, received a diagnosis at just one month old, when she was still in a neonatal unit. Dasha, who lives in Oxfordshire, said: “For us, getting a diagnosis really helped us to understand what to expect. Compared to families who came before the condition had an official diagnosis, we were lucky. We were given a leaflet based on the experiences of other families, and through that we knew she would need physiotherapy and occupational therapy. We learned that Sofia may have heart conditions, and a heart scan revealed that she needed surgery. She had a heart operation at 2 months old, and after that she really started to make good progress, and we were able to take her home from hospital.
“We’re also incredibly grateful to be part of this community. Very few people are living through this experience, and it feels like Jessica and Mungo are like family to us. It’s invaluable, and it’s only been possible because they took part in the study and got a diagnosis, which is now helping others to get there much faster.”
The study is entitled “Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland”, and is published in the New England Journal of Medicine.