Thousands of people diagnosed with rare genetic diseases in major research study
Around 5,500 people with severe developmental disorders now know the genetic cause of their condition, thanks to a nationwide study which will help improve diagnosis across the world: April 2023
More than 13,500 families from 24 regional genetics services across the UK and Ireland were recruited to 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 and likely to be caused by a single genetic change. The Wellcome Sanger Institute 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 have so far been able to provide genetic diagnoses for around 5,500 children in the study, now published in the New England Journal of Medicine. The diagnoses were in over 800 different genes, including 60 new conditions previously discovered by the study. Around three-quarters of the conditions were caused by spontaneous mutations not inherited from either parent.
The research team also found that the chances of success in getting a diagnosis was lower in families of non-European ancestry, reinforcing the imperative to increase research participation for under-represented groups.
A similar approach to diagnosing individuals with rare diseases is being used in the NHS for acutely unwell children with a likely monogenic disorder, which can provide a genetic diagnosis for babies and children in or facing critical care within just ten days.
The Scottish Clinical Exome Sequencing Service provides this pathway for families in Scotland. Through funding from the Chief Scientist Office, the Genomic Data Analysis Centre - a University of Edinburgh facility located at the Institute of Genetics and Cancer, supported by the MRC Human Genetics Unit - is participating in this NHS Scotland programme to conduct trio whole exome sequencing for families with a child with a developmental disorder.
The genetic conditions identified in the current study will feed into the tests applied by the services, 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 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
Getting the right diagnosis can guide clinical care, and brings together families in support networks that can help guide treatment and support pathways, reducing the isolation of having a child with an ultra-rare condition.
When Jessica Fisher was given a diagnosis for her son Mungo’s rare genetic disorder, 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.
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.
We’re 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.
David FitzPatrick and Stuart Aitken of the MRC Human Genetics Unit are authors on the paper entitled “Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland”, published in the New England Journal of Medicine.
- Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland, published in the New England Journal of Medicine
- DDD study website
- The Genomic Data Analysis Centre