A challenge of rare disease: Roanoke woman went undiagnosed for nearly seven decades

Susan Wallace lived nearly all of her 69 years not knowing why she was different from most people she met. Her odd constellation of symptoms was a mystery to her family too.

There were developmental disabilities, the cleft palate, a speech impediment, and worst, periodically debilitating psychological problems that kept her on a cocktail of drugs to manage them.

It was only in her late 60s, when she was in Carilion Clinic Roanoke Memorial Hospital recovering from hip surgery, that a physician who had noted her range of issues asked her older brother, Bill, if she had ever been diagnosed with DiGeorge syndrome, also known as 22.q.11 deletion syndrome. She hadn’t, but genetic testing soon proved the doctor’s diagnosis correct.

Susan died of cancer in early April. The same day, Bill Wallace’s grief was interrupted by a voice on WFIR radio talking about, of all things, DiGeorge syndrome.

The voice belonged to Anthony-Samuel LaMantia, professor and director of the Center for Neurobiology Research at the Fralin Biomedical Research Institute at VTC, who was being interviewed about his decades-long study of the disease. He’s one of many investigators at the Fralin Biomedical Research Institute who study rare diseases, including the deadly brain cancer glioblastoma, Fabry disease, the pediatric cancer diffuse midline pontine glioma, and a genetic heart disease called Brugada syndrome.

Rare Disease Day is recognized internationally this year on Feb. 29. More than 7,000 rare diseases affect 30 million people in the United States, according to the National Institutes of Health. Nearly 1 in 10 Americans is facing a rare disease. 

That someone was seeking answers to the disease that had so affected Wallace’s family was a comfort. That it was going on walking distance from his South Roanoke home was stunning.

Soon Wallace was on the phone with LaMantia, who is also a professor in Virginia Tech's Department of Biological Sciences.

“It was just so comforting to hear from somebody who has devoted his professional life to something that I didn’t even know existed a handful of years ago,” said Wallace, a retired Roanoke attorney. LaMantia’s work was cited in Susan’s obituary, and mourners were invited to make gifts to 22q Family Foundation in lieu of flowers.

“At a time that our family was profoundly sad, this news was incredibly uplifting,” Wallace said.

Taking on a rare disease

LaMantia’s lab is one of perhaps 10 in the world that studies the cellular and molecular basis of DiGeorge syndrome pathology — work that supports developing new strategies for better diagnosis and treatment for individuals with the syndrome

Fewer than 200,000 in the U.S. have been diagnosed with DiGeorge, which affects about 1 in 2,000 births, and it is now part of the standard genetic screening in pregnancies.

The gene deletion that causes DiGeorge syndrome occurs in utero, as the brain is being built – before there’s a means to detect it. The disease’s cascading effects include cardiovascular problems, craniofacial developmental issues, and as children grow older, autism spectrum disorder and schizophrenia. By the time those symptoms are recognized, it’s long past the opportunity for a medical intervention.

LaMantia, however, is investigating the possibility of a narrow window, before final connections are made in the brain, when a therapeutic intervention might be possible.

With such a long list of potential effects, the syndrome presents in a wide range of ways. Some people are high-functioning and undiagnosed because of that. Children with cardiovascular impacts often die in infancy.

Susan Wallace’s symptoms fell into the middle of the spectrum. She was bright and capable, her brother said, and therefore painfully aware that she was not typical.

“She made her way through the world with a lot of strength at a time when there were few to no accommodations for children with special needs,” Bill Wallace said.

She played piano and loved to paint, knit, crochet, and do needlepoint.

“She loved athletic competition and she proudly displayed her Special Olympics medals for swimming,” Wallace recalled. She thrived working at Goodwill Industries of the Valleys and thrilled in collecting her own paycheck.

“Her best day was any day she got to go to Dairy Queen,” Wallace said. “She was a real example for the rest of us in a lot of ways. She had some qualities that I wish I had.”

Knowing you’re not alone

Wallace met LaMantia in person in his laboratory earlier this month. Hearing Susan’s story, LaMantia told Wallace, keeps him mindful of why he continues to pursue DiGeorge syndrome 20 years after he started.

“We’re really excited to contribute to figuring it out,” he said, “but on the other hand you have to be humbled before the problem. I'm not going to solve it, but I think it is important, particularly for rare disorders that don’t get as much attention, to recognize that you're actually working on something that could impact somebody’s life.”

Just the knowledge of the diagnosis, and that somebody is working on the disease had its own powerful impact, Wallace explained. Susan and Bill’s parents died years earlier never knowing what had caused Susan’s struggles.

“Sometimes what we do seems esoteric,” LaMantia said. “But I think knowing you’re not alone, and that there’s somebody who cares and is trying to help is valuable. And for us, being part of a larger effort to really understand a disease that affects lives and families like yours important.”

“From where our family stands,” Wallace replied, “I can't really think of anything more important.”