MADISON, Wis. – Imagine experiencing your child born seemingly healthy, but then struggle to grow, walk, learn or talk – and not be able to tell what is causing it.
Danelle McGuire felt this despair for 14 years.
Her son Treyson Wallace was born in May 2009, after a normal 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 what his doctors described as “club foot” , a condition in which one or both feet are turned inward and downward, affecting normal movement. His doctors told McGuire to massage them and eventually therapy to help straighten his feet.
As Wallace grew older, he continued to miss key developmental milestones, McGuire recalled, and it became clear something larger was going on. McGuire and Wallace moved to Portage, but continued to seek care at UW Health.
At age 7, after undergoing test after test that continued reveal no clues as to what was causing his condition, the family was referred to the neuromotor clinic at the Waisman Center on the campus of the University of Wisconsin–Madison, near the American Family Children’s Hospital. There, over time, they began working with Dr. Janet Legare, a developmental pediatrician at UW Health who specializes in neuromotor disorders. Wallace initially saw her annually, but eventually transitioned to visits every other year.
The clinic offers comprehensive care, therapies, and medical equipment for children with severe neurological and cognitive impairments, as well as provides resources and support for their parents. As a multidisciplinary clinic, it includes speech therapists, social workers, occupational and physical therapists and audiologists.
Wallace had a rare collection of symptoms, but what made his case unique to Legare was he never significantly improved, but never regressed in his development, and this made her think that whatever was going on with him was unlike any other child they had seen and that it may be something genetic, she said.
“Treyson is a unique individual; he’s always such a happy boy,” Legare said. “He has a lot of unique challenges.”
Supporting this idea was the fact that previous genetic testing did not reveal any clues, so with Legare’s help, McGuire was able to arrange insurance coverage for a whole genome genetic sequencing in 2021 that would present a vastly more detailed picture of Wallace’s genetic makeup, and maybe provide the long-sought answer to what was causing his condition.
This advanced testing is only available at select centers around the world, but fortunately, the University of Wisconsin School of Medicine and Public Health has a center with this capability – literally 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.
“We evaluate patients with rare genetics 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 called this process the “diagnostic odyssey”, a journey that many rare disease families endure for years, and sometimes, as in Wallace’s case, more than a decade.
McGuire, Wallace and his father provided DNA samples to Webb in April 2022, and then they had to wait – again – for more than a year. But, the wait was worth it.
In November 2023, they got a call from Webb – there was a result.
McGuire didn’t really believe it would amount to much.
“When they called mt to tell me they had a result, I thought ‘that’s good, but at first I thought they won’t have an answer for me because that’s how all the other tests went,’” she said.
But, this time was different.
“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.”
Wallace has a very rare condition caused by a mutation in the AGO1 gene, which causes a neurodevelopmental disorder with language delay and epilepsy. While only a few hundred people in the world have this condition, 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 the Wisconsin Medical Journal. Wallace is the 40th known case with this genetic disorder to date.
“It’s a wonderful feeling when we are able to identify a change that we believe to be disease-causing, because we are excited to give that information back to the family,” Webb said.
The benefits of these discoveries are more than just for the individual families when it comes to rare disease cases, because their discovery can lend to a growing body of information on each rare disease, she said.
Also, armed with diagnosis, Webb and her team were able to provide guidance on care and help 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.
The diagnosis has given McGuire peace of mind knowing, finally, the cause of her son’s condition, but it doesn’t really change much about her daily life and Wallace’s care, she said.
It did, however, give her the knowledge of knowing his condition was not her fault and that they are doing the right things for him, McGuire said.
“Not knowing and it taking this long, I thought was it something that I did?,” she said. “When they told me that this wasn’t anything that I did, it was a huge relief.”
Throughout this journey with her son, the importance of getting a break from time to time was immensely important, according to McGuire.