Thousands of people diagnosed with rare genetic diseases in large research study

​​​​​​​Around 5,500 people with severe developmental disabilities now know the genetic cause of their condition, thanks to a nationwide study that will help improve diagnosis worldwide.

More than 13,500 families were recruited from 24 regional genetics services in the United Kingdom and Ireland for 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 families had children with a severe developmental disorder that was undiagnosed despite previous testing by the National Health Service and was likely due to a single genetic change. The Wellcome Sanger Institute sequenced all the genes in the genomes of the children and their parents to search for answers, a search that is ongoing.

More than 800 genes involved in the diagnoses

Combined with other high-tech methods, the team has so far been able to make genetic diagnoses for about 5,500 children as part of the study, which has now been published in the New England Journal of Medicine. The diagnoses involved more than 800 different genes, including 60 new conditions discovered earlier in the study. About three-quarters of the diseases were caused by spontaneous mutations not inherited from either parent.

The research team also found that the chances of a successful diagnosis were lower in families with non-European ancestry, reinforcing the need to increase research participation among underrepresented groups.

A similar approach to diagnosing individuals with rare diseases is used in the National Health Service (NHS) for acutely unwell children with a likely monogenic disorder, so that a genetic diagnosis can be made in as little as ten days for babies and children who are in or require treatment in intensive care.

The Scottish Clinical Exome Sequencing Service provides this pathway for families in Scotland. With funding from the Chief Scientist Office, the Genomic Data Analysis Centre - a University of Edinburgh facility at the Institute of Genetics and Cancer, supported by the MRC Human Genetics Unit - is participating in this NHS Scotland programme to perform trio whole exome sequencing on families with a child with a developmental disorder.

The genetic conditions identified in the current study will inform the tests used by the services to help diagnose more people more quickly.

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 the diagnosis affects families

The correct diagnosis can guide clinical care and brings families together in support networks that can help guide treatment and support pathways and reduce the isolation of having a child with a very rare condition.

When Jessica Fisher received a diagnosis for her son Mungo's rare genetic disorder, she initially felt it was all too late. Mungo's condition, called Turnpenny-Fry syndrome, was discovered in 2015 as part of the Deciphering Developmental Disorders study in which he had participated. But by then he was already 18 years old - Jessica, from St Austell in Cornwall, had been through years of uncertainty, not knowing how her son's development would unfold.

However, she found comfort in the fact that through the trial she got in touch with another family who had recently been diagnosed and started a Facebook support group. The group has since brought together some 36 families from around the world, becoming 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 with a wide forehead and thinning hair. Other common problems include feeding problems, severe constipation, and a number of potential issues in the brain, heart, circulation system, and bones.

For Dasha Brogden, the support group has been a lifeline. Her daughter Sofia, who is now almost three years old, was diagnosed at just one month old while still in the 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.

Related Links

Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland publication

DDD study website

The Genomic Data Analysis Centre

MRC Human Genetics Unit

Institute of Genetics and Cancer

Professor David FitzPatrick profile 

Dr Stuart Aitken profile