MADISON, Wis. – Imagine how it would feel to have a child born seemingly healthy, but then he struggles to grow, walk, learn or talk – and no one can figure out why.
Danelle McGuire felt this despair for 14 years.
Her son Treyson Wallace was born in May 2009 after an uncomplicated pregnancy, McGuire said, but soon after birth he failed a newborn hearing screening.
“That was the first indication something was wrong,” she said.
Wallace was also born with a condition called clubfoot in which one or both feet are turned inward and downward, affecting normal movement. His doctors told McGuire to massage them and pursue physical therapy to help straighten his feet.
Wallace continued to miss key developmental milestones as he grew, McGuire said, and it became clear something larger was going on. The family moved to Portage but continued to seek care at UW Health.
After extensive testing did not lead to a diagnosis, the family was referred to the neuromotor development clinic at the Waisman Center on the campus of the University of Wisconsin–Madison, near the American Family Children’s Hospital. They began working with Dr. Janet Legare, a developmental pediatrician with UW Health Kids, and clinical professor at the UW School of Medicine and Public Health who specializes in neuromotor disorders.
The clinic helps children with severe neurological and cognitive impairments meet their optimal potential, according to Legare. The team includes a physician and specialists with expertise in speech therapy, social work, physical and occupational therapy, palliative care and audiology.
Wallace’s case was unique due to his unusual array of symptoms and their relative stability, since neither significantly improved nor regressed in his development.
“Despite the unique challenges he faces, Treyson is always such a happy boy,” Legare said.
While previous limited genetic testing did not reveal any clues, Legare suspected there might be an underlying genetic cause for his symptoms. She referred Wallace to the UW Undiagnosed Disease Program in 2021, the year the program launched, for whole genome sequencing. This type of sequencing offered a more detailed picture of his genetic makeup.
Whole genome sequencing is a form of advanced testing only available at select centers around the world, but fortunately the UW School of Medicine and Public Health offers this option – right across the street from the Waisman Center.
Legare referred McGuire to Dr. Bryn Webb, director of the Undiagnosed Diseases Program at the UW Center for Human Genomics and Precision Medicine, whose program also recently joined the National Institutes of Health Undiagnosed Disease Network as a Diagnostic Center of Excellence.
“We evaluate patients with rare genetic symptoms in cases where other genetic testing has failed to provide an answer,” Webb said. “Many of our patients have gone from doctor to doctor to doctor in search of a diagnosis but have been unable to find an explanation for why those symptoms are happening.”
Webb refers to this process as the “diagnostic odyssey,” a journey that many rare disease families endure for years. Sometimes, as in Wallace’s case, the odyssey can span more than a decade.
McGuire, Wallace and his father provided DNA samples to Webb in April 2022. The wait for results took more than a year but provided definitive answers.
“Dr. Webb said, ‘we have some results and I thought, ‘Wow, I can’t believe it.’” McGuire said. “I can’t believe they are going to tell us what this is, and when they told us it was something super rare, I was even more in shock.”
Wallace has a very rare condition caused by a mutation in the AGO1 gene, which causes a neurodevelopmental disorder with language delay and epilepsy. Only a few hundred people in the world have this condition, and the combination of this mutation with Wallace’s unique set of physical and neurological symptoms places him in extremely rare company, according to research Webb published in Wisconsin Medical Journal. Wallace is the 40th known case in the world with this genetic disorder.
“It’s a wonderful feeling when we are able to identify a genetic change that we believe to be disease-causing, because we are excited to give that information back to the family,” Webb said, explaining that such discoveries both benefit individual families and help build foundational knowledge about a rare genetic disease.
Armed with the diagnosis, Webb and her team guided Wallace’s clinical care and helped Legare and her team understand what therapies to use and what to avoid. Webb’s team also put McGuire in touch with the AGO1 community through a Facebook page and advocacy website.
Throughout this journey with her son, the importance of getting a break from time to time was immensely important, according to McGuire. Through a program offered in Columbia County, she was able to connect with Halley Harms, a respite provider, who provides overnight care twice a month.
Although the path toward a diagnosis was prolonged, the information has given McGuire some peace of mind and relieved her from the unease of wondering whether Wallace’s condition was preventable in any way.
“When they told me that this wasn’t anything that I did, it was a huge relief, but also we know we did the right things for him,” she said. “How much he’s progressed from being a baby until now, he’s progressed leaps and bounds.”