March 27, 2024 | Erin Bluvas, bluvase@sc.edu

Rachel and Brian Clouse could tell their daughters, Liv and Amanda Joy, were developing a little differently from the textbook milestones they’d read about.

“Both walked late, though Liv quickly caught up,” Rachel says. “Amanda continued to fall behind her peers socially and had difficulty focusing.”

They looked to pediatricians, teachers, counselors and therapists for answers, but they wouldn’t find them until the girls underwent genetic testing in 2010. Liv and Amanda were 10 and eight years old when they were diagnosed with fragile X syndrome, and Rachel was identified as a carrier of the FMR1 premutation.

Carried by 1 in every 151 women, this genetic variant can result in fragile X syndrome when passed on to their children. It can also cause age-related decline among carriers – potentially adding health challenges (premature menopause, neurogenerative disease, autoimmune/chronic pain disorders, depression/anxiety, social impairments) to the weighty responsibility of serving as lifelong advocates – if not caregivers – for their children with fragile X.

Though relieved to have a diagnosis, the Clouses spent years with more questions than answers. The limited existing research focused on males with fragile X syndrome, and the stories shared by other families (none of them close by) revealed drastically different experiences to their own.

“The difficulties faced by our girls were much less severe and so different from families we met with boys that it felt like an entirely different condition,” Brian says. “Yet, at least for Amanda, life was challenging enough that we knew we had to find her people – a place where she could be herself.”

Finding a way forward

Then two major things happened. Inspired by the wonderful experiences Amanda had during a special sleep away camp, the Clouses moved from Florida to Boston, where several of her campmates lived and the family had other connections.

They made the move in 2019, and both of their teenage daughters quickly found communities in which to thrive. Amanda enrolled in a school that supports kids with special needs, and Liv embarked on a journey to complete a college degree – ultimately securing full-time employment and living independently. Now 21, Amanda is a student in a college-based transition program that helps neurodiverse children develop into adulthood with life skills classes – living in a dorm and learning how to hold jobs, manage budgets, cook, etc.

A second major milestone in the Clouses' story was the day they met communication sciences and disorders (COMD) associate professor Jessica Klusek and psychology professor Jane Roberts. It was 2023, and Klusek was conducting one of several National Institutes of Health-funded projects to better understand the impacts of the FMR1 premutation on the women who carry it.

Rachel came across a recruitment flyer and enrolled as a participant. She and Brian were so excited to learn that USC had researchers working on various aspects of fragile X syndrome – scientists who were addressing the lack of research on females and who adopted a whole-family approach – that she flew to South Carolina to meet the scientists.

Even though the LivJoy Foundation would not be officially established until later that year, the Clouses were full of enthusiasm for the ways that the nonprofit organization could help improve the quality of life for females with fragile X syndrome. Based on their own experiences raising two daughters, they knew that there was more work to be done to support the unique needs of this population across the lifespan – from screening and testing to achieve earlier diagnosis to providing proper services and social supports and transitioning into adulthood.

They are also passionate about supporting mothers who are carriers and would love to fund research to identify infertility challenges and screen/address the age-related decline that can accompany the FMR1 premutation.  

Partnering with experts

Rachel and Brian couldn’t believe they had found a core of researchers – Klusek and Roberts along with COMD assistant professors Abigail Hogan and Liz Will – who were working on all of these areas. Their collective research has made significant contributions to understanding the communication difficulties, anxiety, intellectual disability, development trajectories and other areas that impact individuals with fragile X syndrome and their families.

In fact, USC ranks No. 2 in the nation for NIH funding to support clinical/human research on fragile X syndrome. What’s more, they intentionally design their studies to ensure that girls and women are represented to help fill the gaps of what is known about their unique experiences.

“When we first moved to Boston, we were surrounded by some of the best medical specialists in the country, but even they could tell us very little about fragile X syndrome and almost nothing about girls who have it,” Brian says. “We also realized that it’s very likely that because their symptoms are different and often more subtle, many girls are not diagnosed until much later than boys if they are diagnosed at all.”

“If it weren’t for Amanda’s diagnosis, we wouldn’t have realized Liv had fragile X syndrome too, and I wouldn’t have tested for the premutation, which would have been great to know about much earlier in life,” Rachel adds. “What we do know is that girls and women with fragile X syndrome need to find their people to thrive, and we need to understand a lot more about their experiences in order to connect them with the right supports to make that happen. That’s what the LivJoy Foundation is all about.”

“From the first time I spoke with Rachel on the phone, we were 100 percent on the same page about needing to address the knowledge gap on girls,” Klusek says. “In my career, I have seen over and over that it is just harder to get grants focused on girls funded. We get grant reviews back telling us we should be studying boys instead because girls 'aren’t as affected.’ Even when we overcome that critique, studying girls can be more complicated methodologically, which makes it harder for these grants to score well in peer review.”

“While almost all boys with fragile X have intellectual disability, girls show more variability with symptoms ranging from intellectual disability to learning disabilities to having no symptoms at all,” she adds. “This introduces measurement issues that we don’t have to deal with in studies on boys. Our assessment tools are often not designed to capture such a wide range of abilities, and that can make things messy. More variability also means that you need a larger sample, which makes research on girls more expensive as well. It is just such a classic example of underrepresentation of women’s health issues in research. It has always bothered me.”

Reframing the future

That common ground is where the Clouses formed their partnership with USC. Knowing that they had found a unique team of experts and that public research funding is often tied to studying males, they were eager to help carve a path for a line of research that would focus on this understudied area.

After discussing a number of ways to move forward, the Clouses decided to make a generous gift that would fund a four-year postdoctoral fellowship to support the training of an early career scientist who is committed to advancing knowledge and improving outcomes for females with fragile X syndrome.

“A postdoctoral fellowship that offers training and mentorship from multiple fragile X experts is one of the key ways to address this gap and to ensure that future research is inclusive of this understudied population. The fellowship is an investment in the next generation of scientists who will continue this work in the future,” says Klusek. “Opportunities like this fellowship are just so important. It can be really difficult to attract junior scientists into the fragile X field and keep them there because it is so specialized. And even when the interest is there, it can be hard for trainees to get their foot in the door. For example, fragile X is relatively rare, so accessing this patient population, even just for a pilot study, is expensive and requires resources that postdocs typically don’t have.”

“On top of that, the field is small, so the pool of potential scientific mentors is small. Many of our top fragile X researchers are clustered at research institutes that don’t have doctoral programs, so we are not graduating many Ph.D.s with fragile X training,” she says. “And once a trainee does identify a mentor, the mentor needs to have funding available to support the trainee. The LivJoy Postdoctoral Fellowship addresses all of these challenges. And that is going to make a huge impact.”

This is exactly the type of impact the Clouses are looking to make.

“Based on our experiences as parents and advocates, we know that many females with fragile X are more than capable of living independent lives; they just need the proper support,” Brian says. “They are most held back by social, psychological and communication challenges, and USC researchers are addressing all of these areas. It couldn’t be a better fit for LivJoy’s mission to help girls with fragile X live their best lives.”

Though LivJoy is in its infancy, they have big plans for it. The Clouses want to make it easier for families to find resources and connect with one another. This may take shape as a directory for girls with fragile X, where families can find a hub of information that includes everything from genetic testing to social groups (e.g., therapeutic, camps, schools). They also plan to invite others to join their fundraising and grant distribution activities.

“There’s a range of how fragile X affects females, and we want to support girls and women with every type of experience,” Rachel says. “Our goal is to find, fund and share programs that enable these individuals to live a life full of joy and to make it easier for their families to connect them with what they need for every stage of their journeys.”

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