Thousands of patients with severe, difficult-to-diagnose developmental disorders finally received answers, thanks to advanced genetic testing and extensive collaboration, according to a study published Wednesday in The New England Journal of Medicine.
The Deciphering Developmental Disorders (DDD) project performed advanced DNA sequencing on nearly 13,500 participants in the United Kingdom and Ireland, with its first patients recruited in 2011. A collaboration between the U.K. National Health Service and the Wellcome Sanger Institute, it involved 24 referring clinics working together, with the goal of each new diagnosis potentially fueling answers for similar patients.
When participants—mostly children—were enrolled in the study, they were living with unidentified neurodevelopmental disorders, “birth defects,” unusual growth patterns, dysmorphic features, odd behaviors, and/or diagnoses of genetic disorders with no known cause.
Most had previously received some genetic testing, but no “next generation” testing and nothing extensive—and none have received a definitive diagnosis.
“The families in our study were desperate for answers, which can make a huge difference to clinical management and quality of life,” Caroline Wright, professor of genomic medicine at the University of Exeter, said in a news release about the study.
“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.”
The promise of clinical trials, and the trouble with silos
Researchers noted how patients presented, and allowed algorithms to assist in the evaluation of genetic variants detected. If a diagnosis wasn’t readily found for a patient, that patient’s genetic data was repeatedly screened against new information acquired by the study as time went on.
More than a decade into the project, 60 new conditions have been discovered, nearly 300 journal articles have been added to the body of literature, and diagnoses have been made in more than 800 different genes, according to the release.
The study shows the importance of using a variety of genetic testing approaches; performing broad analyses that don’t presume the genetic cause of a disorder; sharing data; working collaboratively; and continuing to screen the data of undiagnosed patients against newly discovered findings, the authors assert.
“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,” Matthew Hurles, director of the Wellcome Sanger Institute and honorary professor of human genetics and genomics at the University of Cambridge, said in the release.
For many patients, diagnoses only happened because data was combined from patients throughout the U.K. and Ireland—and for some patients, diagnoses only came because of communication with international colleagues, he added.
The potential to benefit millions globally
The authors credit the study’s success to “the fusion of clinical expertise, genomic sequencing, and bioinformatics,” which can “drive diagnosis and discovery” for families failed by older, more limited, less dynamic genetic testing.
The study “adds to the growing body of evidence that genomic testing should be a first-line test for all patients with a suspected genetic disease,” Ryan Taft, vice president of scientific research at biotechnology company Illumina, tells Fortune.
The study also emphasizes the importance of reanalyzing the data of patients who don’t immediately receive answers, “given the almost exponential increase in our understanding of the genetics of these disorders,” Taft adds.
It’s a sentiment echoed by Hurles, who emphasized the importance of undiagnosed patients being able to benefit from ongoing research on their data, as the use of genomic technologies become more routine and additional similar patients are discovered.
While the DDD study is no longer enrolling, it will continue to study participant data through 2030, and anticipates that “a few families will continue to receive new diagnoses during this period, as knowledge grows,” according to the study website.
While new rare disease patients won’t directly benefit from the DDD study—though its findings may contribute to their diagnoses—the same and similar technology is becoming increasingly available, as costs plummet and insurance companies realize its cost-saving, and even lifesaving, potential.
Says Taft: “It is relatively easy to identify the patients who can benefit, which include millions of children worldwide with intellectual or developmental disabilities.”
