Loss of funding creates uncertain future for Undiagnosed Diseases Network at Duke

A lack of funding from the National Institutes of Health leaves the future of Undiagnosed Diseases Network clinics uncertain.

Duke Health is one twelve clinics across the country operating in the network. The network reviews applications from patients who have not been able to achieve a diagnosis despite multiple attempts.

Duke’s facility has the ability to do more than the standardized tests available elsewhere — the network has research facilities.

Since its inception, the Undiagnosed Diseases Network has helped thousands of families, uncovering almost 50 new disorders. NIH funding for the UDN is currently set to run out in June of 2024.

A years-long hunt for answers

Two weeks after Ezra Kelly was born, his parents noticed hyper-pigmentation on his skin, but trips to different doctors couldn’t find concrete answers.

"During my pregnancy, we didn’t have any awareness of anything. We did the genetic testing while I was pregnant and everything came back normal," said his mother Nazira Kelly.

Ezra’s pediatrician referred the family to a dermatologist and did a head ultrasound, but at six months old, his seizures started.

"It was the most terrifying day of my life," Nazira Kelly said.

The Kelly family was stationed in Kansas, but when Eric Kelly was transferred to Fort Bragg, the family applied to the Undiagnosed Diseases Network clinic at Duke Health.

"Every day was just worry about, what does the future hold, what should we do," Nazira Kelly said.

Rebecca Spillmann is a certified genetic counselor who worked on Ezra’s case.

She began working at Duke Health when they applied for the UDN grant, and she’s been working on the team ever since. Spillman explained that although Ezra had already done genetic testing, Duke researchers took a different approach.

"We have resources that clinical sites and clinics just don’t have," Spillman said. "We did a skin punch from the hypo-pigmented area on Ezra’s leg, and sent it for whole exome sequencing."

The results showed a genetic change in a gene called MTOR, known to cause Ezra’s symptoms. That variant was in his skin, but not in his blood.

"He essentially has 2 different sets of DNA. The DNA in his blood may not match the DNA in his skin or his brain," Spillman explained.

When he was two years and eleven months old, Ezra received a diagnosis of Smith-Kingsmore Syndrome.

The meaning of a diagnosis

When Ezra was diagnosed, Nazira Kelly said she felt as though she had gone from being in an ocean to a river, swimming with more direction and purpose. The diagnosis of Smith-Kingsmore Syndrome meant the Kellys had a community around them, learning from families in the same situations.

"It was wonderful that when you shared your stories, they said, ‘Oh yeah, I totally understand,’" Kelly said. "Because it was kind of a lonely journey before."

Dr. Vandana Shashi is a professor of pediatrics in the Division of Medical Genetics Divisions. She said getting a diagnosis not only helps a patient and caregivers psychologically, but it also directs the kind care and treatment needed, even if there isn’t a specific cure.

"A diagnosis means hope," Shashi said. "Just knowing why is really big."

The future of funding

Dr. Shashi explained that the NIH initially funded the network in 2014, funding two cycles since. The second cycle ended in June of 2022, but it has been extended to June of 2024.

Sashi said the NIH hopes the existing clinical sites will turn the network into a clinical program, seeing patients, billing insurance, and doing all they do in standard settings. However, she said if the network moves to a clinical model, they are replicating what exists elsewhere.

"What makes the UDN different is the research component associated," Sashi explained. "We can certainly bill patients and do the clinical work, but that research will be lost, and so the value of that research will be lost."

Spillmann believes the loss of funding will lead to an imbalance.

"We’re really going to be creating this inequity of patients who have the ability to travel to a clinical site, patients who have really great private health insurance, versus people who don’t have those funds readily available to pick up and take a week off of work and come to a clinical site to be evaluated," Spillmann said. "We really believe that financial means should not be a barrier to achieve a diagnosis for yourself or your child."

A personal plea

Ezra Kelly’s older sister Zara loves pink, purple, and unicorns.

"She’s a typical princess girl," Nazira Kelly said.

While seven year-old Zara enjoys her toys and treasures, Ezra loves what Zara does.

"He’s always about her, whenever she’s close by, he’s always listening to her," Kelly said. "He really adores her."

Ezra’s diagnosis is not the end of the health journey for the Kellys, but it marked a new chapter.

"His diagnosis is still very new, and there’s not a lot known, but that helps to streamline the process," Kelly said.

The diagnosis has also helped the Kellys come full circle, participating in fundraising and awareness outreach for the Smith-Kingsmore Foundation.

Nazira Kelly hopes other families will have that opportunity for answers from places like Duke Health.

Dr. Shashi said the team is looking at different paths to sustain the UDN, working on philanthropy, fundraising, and partnerships.

Although the NIH has issued funding for a coordinating center, collecting applications and holding data for another five years, the clinical sites have no funding.

"We can certainly bill patients and do the clinical work, but that research will be lost, and so the value of that research will be lost," Shashi said. "The value of the UDN really cannot be maintained in the future unless there’s funding for the research. It’s really the research that takes every patient’s evaluation above and beyond what can already be done."