Arne Cavents was four years old when he was misdiagnosed.
Growing up in a small city in Belgium, Cavents knew he was different from other children. He’d had surgery to correct his inward-turning legs, and had difficulty tying his shoes and riding a bicycle.
Due to his symptoms, he was believed to have Charcot-Marie-Tooth disease (CMT), a progressive hereditary condition that causes muscle weakness in the feet, ankles, legs, and hands. His mother, sister, and grandmother suffered the same issues.
It wasn’t until 2017, when Cavents and his wife started thinking about having children, that he decided to get genetic testing to confirm the diagnosis.
But five years and three hospital visits later, the tests had only ruled out CMT – until he received a call in 2022 from a doctor in Antwerp who had detected an unusual mutation in one of his genes.
Cavents was eventually diagnosed with distal myopathy with early childhood onset, a rare condition that, like CMT, causes weakness in the feet. His doctor estimates it affects one in one million people.
“Finally, we know what is going on,” Cavents, a 32-year-old health insurance agent, told Euronews Health.
He said the diagnosis was “a great relief” after years of “uncertainty, sadness, hope, [and] disappointment”.
Cavents is one of hundreds of patients with previously unknown genetic conditions who got answers as a result of a European programme to give them a second chance at diagnosis.
By definition, these conditions affect fewer than five people per 10,000, and about 80 per cent have genetic origins.
On average, patients wait 4.7 years before they are diagnosed, with younger people facing longer delays that can make it harder to find the right treatment, according to a 2022 survey of more than 10,000 rare disease patients across Europe.
Diagnosis “is really the first step,” Roseline Favresse, head of research policy and initiatives at the advocacy group European Organisation for Rare Diseases, told Euronews Health.
As part of a study published in the journal Nature Medicine this year, researchers from 37 medical centres across Europe pooled their data and reexamined the records of about 6,500 rare disease patients who did not have a genetic confirmation of their diagnosis, as well as 3,200 relatives.
This data-sharing partnership, known as Solve-RD, allowed researchers to analyse more recent studies on gene mutations, use cutting-edge technology to identify potential variants, and consult experts in other countries – a key component because these conditions are so rare that many diagnosticians lack expertise in any one particular disease.
“By having novel software tools to mine the data, with existing data you can make a new genetic diagnosis,” said Richarda de Voer, an associate professor of cancer genomics at Radboud University Medical Centre in the Netherlands, who worked with Solve-RD to diagnose rare hereditary cancers.
What a diagnosis means for patients
As part of the Solve-RD programme, more than 500 people were diagnosed with rare neurological disorders, severe intellectual disabilities, muscle diseases, hereditary gastrointestinal cancer, and other conditions.
For about 15 per cent of them, diagnosis led directly to new treatment options or other medical support. For the rest, it offered clarity and hope that new treatments could become available in the future.
“These disorders are rare, they are genetic, and in the past, we would say they are not curable,” Dr Jonathan De Winter, a rare disease researcher at the University of Antwerp and Cavents’ doctor, told Euronews Health.
“But that's really changing in the past years,” he added.
For Cavents, his diagnosis opened the door to fatherhood after years spent worrying he could pass his condition on to his children.
He and his wife will now have the option to monitor for the genetic variant through prenatal diagnostics or during in vitro fertilisation (IVF), in which embryos would be tested for the mutation before being implanted into his wife’s uterus.
Despite the lack of treatment options for Cavents at present, his diagnosis has been so life-changing that he and his wife sometimes joke about naming their future child after De Winter.
“It's been a long road. In the end, it is a positive outcome for me,” he said.
What’s next for genetic diagnostic research
The Solve-RD programme ended in 2024, but its early findings are central to a new international project that aims to improve prevention, diagnosis, and treatment for Europe’s 30 million rare disease patients.
Through the new project, known as the European Rare Disease Research Alliance (ERDERA), researchers are working with bigger genetic datasets and incorporating more advanced genome sequencing technology that should help them detect complex mutations.
“We use the lessons learned from Solve-RD for ERDERA,” Alexander Hoischen, a geneticist and professor at Radboud University who co-led the Solve-RD project, told Euronews Health.
“We are now already more efficient in making diagnoses,” he added.
As a result, clinicians should be able to share some potential new insights with patients within the next year, according to Holm Graessner, a rare disease researcher in Germany who worked with Solve-RD and now co-leads ERDERA’s clinical research network.
“We now have the chance to… scale it up, to further develop it, and to include further countries,” Graessner told Euronews Health.
As researchers take those steps, patient advocates want the programme to move beyond academic settings to make genetic reanalysis available in all clinics that treat rare disease patients.
“What we hope to see is a significant increase in the percentage of cases solved after reanalysis,” Favresse said, as well as “equal opportunities for everyone to benefit from a second chance at being diagnosed”.
