EXETER, United Kingdom — Around 5,500 children with severe developmental disorders now know the genetic cause of their condition. The revelations that these individuals are dealing with rare genetic diseases is giving parents hope that a treatment for these conditions could be on the way.
“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,” says lead author Caroline Wright, Professor of Genomic Medicine at the University of Exeter, in a media release.
A decade ago, researchers say more than 6,000 children were being born in the United Kingdom with a genetic condition that was likely going undiagnosed every year. That experience is now changing, thanks to the Deciphering Developmental Disorders (DDD) project. Study authors hope it will revolutionize patient care.
“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,” Prof. Wright continues.
The project recruited more than 13,500 families from 24 regional genetics services across the U.K. and Ireland. There are about 7,000 known rare diseases which affect less than 0.5 percent of the population. Five new ones are described in the medical literature every week. Most are genetic, resulting from mutations in a person’s DNA.
Some are familiar, like Huntingdon’s disease or cystic fibrosis. Others, however, affect just a handful of people throughout the world. All the families in this study had children with a severe developmental disorder which was undiagnosed despite prior testing through the National Health Service (NHS) and likely resulting from a single genetic change.
The Wellcome Sanger Institute in Cambridge sequenced all the genes in the children’s and parents’ genomes to look for answers, a search which is still ongoing. Combined with other high-tech methods, the team identified over 800 different genes and 60 conditions new to science. Around three-quarters result from spontaneous mutations not inherited from either parent.
“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 centers 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,” says 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.
Hurles adds that responsible data sharing was critical for making the diagnoses. The study in the New England Journal of Medicine also used a tool called DECIPHER to compare the mutations in a database of thousands of patients worldwide.
“Embedding a powerful informatics platform at the heart of this study facilitated the collaboration with families, clinicians and scientists engaged in the project, and played a crucial role in its diagnostic success and in the discovery and ultimately treatment of new causes of rare genomic disease. The Deciphering Developmental Disorders study has resulted in more than 290 publications and identified approximately 60 new disorders,” explains senior co-author Helen Firth, also a professor from Cambridge.
The British team notes that a similar approach to diagnosing individuals with rare diseases is in use at facilities within the NHS.
“From the initial design of the study, through the building and sustaining of collaborative partnerships with clinicians, to the identification and addressing of practical ethical problems in real time throughout the life of the project, the embedding of ethics research and advice into the Deciphering Developmental Disorders project has been crucial to its success and to building and maintaining well-founded trust and confidence of clinicians and patients,” adds senior co-author Professor Michael Parker from the University of Oxford.
The genetic conditions identified in the study will feed into tests to help diagnose more people swiftly.
“We’re creating the most advanced genomic healthcare system in the world and this study is yet another step forward to revolutionizing care for NHS patients,” says U.K. Health Minister Will Quince.
“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.”
Jessica Fisher’s son Mungo suffers from a rare genetic disorder called Turnpenny-Fry syndrome. 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.
It was discovered in 2015 through the Deciphering Developmental Disorders study, in which he was a participant. As he was already 18, Jessica 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.
“When I first saw a picture emailed to me of the other family’s child it was really emotional,” Jessica Fisher says. “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.”
For Dasha Brogden, the support group has been a lifeline. Her daughter, Sofia, now nearly three years-old, received a diagnosis at just one month-old, when she was still in a neonatal unit.
“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,” says Dasha Brogden, who lives in Oxfordshire.
“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.”
South West News Service writer Mark Waghorn contributed to this report.