A healthy baby takes a turn

When Oliver Broner was a baby, his parents Achai and Liz Broner found him so "alert and strapping" that they had a difficult time swaddling him. "He wouldn't stay still," Achai said. "We felt like, wow, you're really strong for how small you are."

However, this changed after Oliver became sick at three months old with a high fever, with physicians being unable to pinpoint a specific cause. Later, the fever subsided, and Oliver was able to go home.

After the fever, the Broners noticed that Oliver's progress in reaching developmental milestones had stalled. Although he had been rolling over, this stopped for several months. He was also slow to sit up and didn't begin crawling until 14 months. He didn't start walking until he was 22 months old, and over time, his movements worsened, to the point where he was often wobbly and had difficulty standing.

Although the Broners brought their concerns to pediatricians, they were just told children develop at different rates and that they shouldn't worry.

According to Liz, the doctors' quick dismissal of their concerns was troubling. "They weren't listening to what we were saying we were seeing," she said, adding that challenging the medical establishment was difficult. "You have this self-doubt as a parent — am I doing enough? We had these experts … you think, they must be right."

Eventually, the Broners were referred to an occupational therapist, who found that Oliver had hand tremors and that his pupils were different sizes. Tests ruled out multiple sclerosis and muscular dystrophy, and an MRI showed no brain damage. A DNA microarray analyzing thousands of genes and genetic variations also didn't find anything out of the ordinary.

Despite a lack of findings, two neurologists told the Broners that Oliver probably had cerebral palsy, which is a group of conditions that affect movement, balance, and posture. Doctors said that no further treatment was available.

However, even with a potential diagnosis, Oliver's medical journey was not over. As Oliver's symptoms worsened over the years, his parents continued to search for an answer, visiting numerous specialists in cardiology, genetics, neurology, and sleep medicine.

The long journey to a genetic answer

After Oliver began experiencing frequent pain without effective treatments, a new neurologist suggested he undergo whole exome sequencing, a type of genetic sequencing that can identify hidden mutations and rare diseases.

In 2019, the Broners met with Seema Lalani, a clinical geneticist at Texas Children's Hospital and a professor in the department of molecular and human genetics at Baylor College of Medicine. At the appointment, Lalani told the Broners something shocking: Oliver didn't have cerebral palsy.

Although Oliver had been diagnosed with cerebral palsy at two years old, Lalani said that "his normal brain MRI and findings on physical examination during our evaluation made this diagnosis less likely." At the time, Lalani suggested that Oliver's symptoms could be ataxia, which is a neurological condition that makes movement and coordinating difficult. However, this diagnosis also turned out to be incorrect.

Emrick recommended Oliver try Sinemet, a medication typically used to treat Parkinson's disease. Although the medication didn't seem to work at first, increasing the dose made it more effective, and Oliver was able to walk, jump, and climb stairs without help.

"We were showing him off to everyone — it was such a good moment, we felt that changed the quality of his life," Achai said. "It didn't stop the progression, but slowed it."

However, since Oliver still didn't have an official diagnosis, his parents submitted his case to the Undiagnosed Diseases Network, an NIH-supported program that studies health conditions of patients that aren't able to get a diagnosis elsewhere.

Through the program, the Broners met another patient who had the exact same DNM1L variant and similar symptoms. They also connected with Michael Wangler, a pediatrician, researcher, and medical geneticist at Baylor College of Medicine who studies the DNM1L gene in fruit flies, and enrolled Oliver in Wangler's research study.

By studying fruit flies, Wangler discovered that variants in one region of the DNM1L gene are associated with more severe symptoms than those found in Oliver's region. Oliver's variant occurred in a different section of the gene and was associated with a more moderate set of symptoms.

It took almost two years for Wangler's lab to engineer fruit flies to carry an equivalent mutation to Oliver's. Ultimately, Wangler found that, much like Oliver, the flies had difficulty with movement, which showed that the variant disrupted the gene's normal function.

As Wangler's genetic research progressed, Oliver's doctors eventually agreed that the DNM1L variant was the cause of his symptoms. The gene variant is now part of Oliver's official record, and his exome analysis has been reclassified to identify the DNM1L variation as "likely pathogenic" instead of "unknown significance."

How Oliver is today

Oliver, who is now 15, continues to require help to manage his condition. He has an aide who accompanies him at school, and while he can walk inside the classroom, he travels to and from school in an electric wheelchair. He also takes different medications to help him manage his pain and difficulty walking.

"It's not ideal, but I could have it a lot worse," Oliver said. At the same time, he continues to be a typical ninth grader in many ways. He likes video games, mystery books, and scary movies. He also recently discovered archery and enjoys hanging out with his friends at the pool.

In general, he's just going through normal life in high school where the other kids generally "treat me like a normal person," Oliver said. "Sometimes they're surprised I'm in a wheelchair, because I walk. But I say it's, like, a genetic thing."

To increase awareness of this rare genetic condition, the Broners launched a foundation for DNM1L-related disorders. The organization raises money for research and helps connect families navigating the condition. So far, the organization has identified 58 DNM1L-related cases worldwide.