Solving medical mysteries with genetics: The Penn Neurogenetics Therapy Center

The Penn Neurogenetics Therapy Center works to achieve a genetic diagnosis for as many patients as possible, and establish clinical trials using novel gene and molecular therapies.

At 44, Janet Waterhouse should have been the picture of health; a former Division I soccer player, she taught yoga, enjoyed running, and didn’t drink alcohol. Despite her healthy and active lifestyle, over a span of decades she experienced a number of unexplained symptoms.

Her symptoms continued to worsen into her 20s when she began to sporadically lose function of her hands and experience severe bouts of vertigo. Most doctors attributed her symptoms to stress and anxiety. During this time, Waterhouse was seeing a pain management specialist, who was concerned enough about her worsening symptoms to run a blood test, where he found irregularly shaped blood cells, called acanthocytes.

A series of serendipitous referrals led Waterhouse to Ali Hamedani, an assistant professor of neurology and ophthalmology in the Perelman School of Medicine. Based on her symptoms and exam, he suspected a genetic condition called chronic progressive external ophthalmoplegia (CPEO) and referred her to Laynie Dratch, a certified genetic counselor in the Penn Neurogenetics Therapy Center, for genetic testing.

In May of 2022, Dratch gave Waterhouse what she had been chasing for decades: a diagnosis. “When the genetic counselor told me they found the genetic mutation they were looking for, I cried for a solid five minutes out of relief,” Waterhouse says.

Waterhouse’s case of CPEO was found to be caused by a variation on her RRM2B gene, which affects the mitochondria in her cells. While the condition is very rare and can sometimes take years to locate and diagnose, Hamedani’s hunch about the gene mutation led them right to it.

Because little is known about CPEO, treatment options are limited. “Most people would be discouraged by the uncertainty,” she says, “but it thrills me to get to be the blueprint. I get to show people how to live with this.”

Launched in March 2020, the Penn Neurogenetics Therapy Center has a team of clinicians, nurses, genetic counselors, and clinical research staff who are devoted to the care of patients with inherited neurological disorders and to participating in clinical trials of novel gene and molecular therapies.

The program’s mission is twofold: first, they utilize the expertise of clinicians and researchers throughout the department of Neurology and across Penn Medicine to achieve a genetic diagnosis for as many patients like Waterhouse as possible, creating a database of eligible patients for new treatments and clinical trials. Second, they work to establish clinical trials using novel gene and molecular therapies for patients with genetically-based neurological disorders.

“Our genetics counselors are some of the best in the country, and are incredibly effective at diagnosing patients and matching them with effective treatments and clinical trials,” says Steven Scherer, a professor of neurology and director of the Neurogenetics Therapy Center. “Now we can utilize this expertise to design tomorrow’s therapies.”

Read more at Penn Medicine News.