Two decades, 46 families and 23 states

When University of Kansas Life Span Institute researchers board a plane to visit families who are enrolled in their Fragile X study, they bring more than a suitcase with clothes. They may lug building blocks, a recipe, or a book about constructing castles, as well as video and photography equipment.

Over the years, the items have varied, and the technology has advanced, but families have been the consistent throughline for more than two decades of KU research. Today the study based at the Fragile X Lab includes a cohort of 46 families across the country participating in what is thought to be the longest-running longitudinal study of Fragile X syndrome. Fragile X syndrome (FXS)is the leading cause of inherited intellectual disability, and while less known to the public, FXS is second only to Down syndrome as the most common genetic cause of intellectual disability.

Led by Professor Nancy Brady, who launched the research with Professor Steve Warren in 2004, the Fragile X project received an additional $2.25 million in 2023 from the National Institutes of Health to fund the project for an additional five years, bringing the total funding for the project to $6.1 million. The additional funding expands the project’s focus on young adults. The study is seeking individuals ages 18-22 years old who have Fragile X syndrome, and their parents. It will identify characteristics associated with successful transition outcomes for young adults with Fragile X syndrome, and further investigate mothers' mental health and functioning. 

The annual visits with families spread across 23 states have helped KU researchers expand what is known about Fragile X syndrome and familial characteristics and behaviors. Longtime participants in the study include Ohio resident Judith Maloney and her family. Her adult sons, Liam and Nolan, were just newly diagnosed toddlers when the study began. Looking back, Maloney said, “I didn't know I was participating in something that was going to last 22 years.”  

During the annual visits from researchers, she and her children answered questions and worked together on structured activities, such as making pancakes or playing a game to build a castle. 

Brady, a senior scientist at the Life Span Institute and professor in the Speech-Language-Hearing: Sciences & Disorders Department, said the research is focused on understanding the variables that predict development as children with Fragile X Syndrome advance to adulthood. It’s also exploring changes among the parents involved in the study.  

“We seek to understand how factors influence employment, communication, adaptive behavior, quality of life, independence, and self-determination as adolescents transition to adulthood,” Brady said. Additionally, Brady said the researchers strive to determine how these various factors influence mothers. The research has explored their executive functioning, anxiety, depression and caregiver burden, partner support, satisfaction with individual education plans for their children, and community support during a child’s transition to adulthood.  

ADJUSTING TO FRAGILE X 

Maloney described Liam, 25, and Nolan, 23, as opposites in many ways.   

Liam didn’t speak until around age 4. He now talks nonstop and has an “amazing” vocabulary, his mother says. He loves video games and lounging and would often prefer to stay in his room doing both.   

"When he's in a situation, he's very social,” Maloney said. “It's a challenge for us to get him out and doing things. But once he’s there, he’s easy. He knows all the typical things that are going on— he knows how to interact. Like, if somebody's talking about football, he’ll say, ‘Oh, the Buckeyes won this weekend.’”  

Nolan is quieter and more introverted, she said. At lunch, he might make a sandwich and when asked if he needs help, he declines the offer. He wants to do everything himself and asserts his independence. 

"He does not care about anything with peers or current events. He couldn't care less,” Maloney said. Nearly 20 years ago, when Nolan and Liam were diagnosed with Fragile X syndrome about one year apart, there was little information available for parents.

Participating in the study, however, was a way to learn more about the condition and to look to the future. While much more is known about Fragile X syndrome today, scientists and families have many unanswered questions.  FXS  is thought to affect about 1 in every 4,000 males and one in every 6,000 females, with about 100,000 people estimated to have the disorder in the United States. It results in mild to severe intellectual disabilities in males with behaviors that include hand-flapping or avoiding eye contact. Speech delays are common, as is attention deficit and hyperactivity. Effects in females are more variable, ranging from no intellectual disability to severe intellectual disability, with or without readily apparent behavioral characteristics. Individuals with Fragile X syndrome also are friendly, social and have strong visual problem-solving skills. 

Additionally, about 1.5 million Americans, sometimes the parents or grandparents of a child with Fragile X syndrome, have smaller premutations of the Fragile X gene. Those premutations can be associated with health issues throughout a person’s lifetime. Some premutation studies are conducted at the BRAIN lab at the Life Span Institute. 

The Fragile X Lab’s longitudinal study has helped researchers understand Fragile X families, including their concerns for their children’s needs in the future. The research has broadened understanding of typical behavior, learning styles, intervention approaches, and the impact on family members.  

RESEARCH IMPACT

During the span of the study, researchers have: 

Provided insights into effective teaching and behavioral intervention methods. Findings published March 2023 revealed adolescent boys with FXS complied with their mother's requests on average about 70% of the time. If the mother increased the frequency of the requests, the child was less likely to comply. 

Documented risks for maternal anxiety and depression. An August 2022 published study looking at mothers of children with Fragile X syndrome found an increased risk of those conditions stemming from potential genetic risk for associated disorders, and to stress associated with parenting a child with significant behavioral, emotional, and educational support needs. 

Drawn attention to the need for transition support for adolescent children. In 2024, KU scientists published research in the American Journal on Intellectual and Developmental Disabilities that language skills and autism characteristics are major concerns for parents, influencing expectations for their children's independence as adults. Children who struggled with communication skills had more challenges finding a job or continuing their education. Researchers said these concerns highlight the need for more comprehensive transition planning addressing these challenges. 

Shown how combined conditions affect behavior. In a study published September 2021, researchers found challenging behaviors, such as aggression or attention difficulties, tended to be higher for individuals diagnosed with both Fragile X syndrome and Autism Spectrum Disorder. Generally, these behaviors improve by age 18, but levels of anxiety and depression remained consistent through that age. In the same study, researchers found mothers who were better able to adapt and change their approach had fewer attention problems from their children as they aged, especially among autistic children diagnosed with Fragile X syndrome.  

Recognized differences between boys and girls. Comparing boys and girls with Fragile X syndrome, researchers found that boys told simpler stories, while girls told more complex stories. These results, published in January 2022, suggest narratives yield valuable diagnostic information and may be potential targets for intervention for individuals with Fragile X syndrome. 

FRAGILE X IN FEMALE POPULATIONS  

While early research on Fragile X in the United States was more focused on boys, it has expanded in recent years to be more inclusive of girls. Fragile X syndrome affects the X chromosome (thus the name). Boys have only one X chromosome, while girls have two; symptoms in girls are usually milder than in boys and can include intellectual disabilities, learning disabilities, attention disorders, and anxiety.  

Jacquelyn Coleman and her adult daughter, Maya, started participating in the KU longitudinal study about one year ago. Coleman, who lives in a suburb of Houston, Texas, thought the study would be a good fit for her daughter since it wouldn’t require traveling, visiting a clinic, lots of tests, or medication.   

"It was just more of a social kind of study, you know? With answering questions and then doing home visits,” Coleman said.   

Her daughter, Maya, struggles with severe anxiety and was nervous before the visit, asking her mother “hundreds” of questions, Coleman said. Once the researchers arrived, however, they both felt much more at ease.  

"Everyone that came was very nice and very pleasant, and respectful,” Coleman said. Coleman says supporting her daughter, who is in culinary school, during her transition to adulthood hasn’t been easy.  “Her anxiety tends to be her most disabling thing. She lacks confidence in herself when she's never done something, and she's afraid to try,” she said. As a parent, that can be challenging to manage, she said. “You're trying to strike the balance between ‘mom wants to fix it’ and trying to help her be an adult.”  

VALUING RESEARCH PARTICIPATION 

While Fragile X syndrome is difficult, both Coleman and Maloney said they haven’t experienced the worst of what they read when they first heard about their children's diagnoses.  

"It's only our experience, but it's so much better than what any book would have you believe their life is going to be like,” Maloney said. "Our kids are so funny. I mean, their sense of humor is out of this world. They get humor, you know? They're really fun to be around.”  

Maloney said their supportive network of family and friends in their community has been incredibly helpful, but she added that partnering with scientists trying to learn more about the disorder has been vital. It’s given them hope that the outlook for their children’s future will continue to improve.  

Coleman is optimistic about her daughter’s future because of the scientific advances as well as the resources available for supporting her — from their close-knit family to programs and opportunities within their community. She encourages other parents like her to participate in research studies with their children.  

"I'm seeing the differences that it makes when you're able to expand the knowledge. And I think the more people who are willing to participate, and the more researchers will get excited about it.” For parents of children who have recently been diagnosed, Maloney offered some encouragement, particularly as research continues to progress. 

“It's not always going to be easy,” Maloney added. “Definitely looking to the future, it's not going to be as bad as you think,” she said.  

Credits:

Writing: Christina Knott
Illustrations: Hannah Hawkins
Layout and design: Marleny Ceron and Hannah Hawkins
Photo of Coleman family courtesy of Jacquelyn Coleman
Photo of Maloney family courtesy of Judith Maloney