Rare disorder impacts, unites family

By Sean Gorman

It didn’t take long for Jill Dolan to notice her daughter, Carly, was experiencing delays in the early months and years after her birth in 2002.

Call it a blend of maternal instincts and training for the mom, who had a background in early childhood education. As an infant lying on her back, Carly wouldn’t reach for toys dangling above her. What’s more, when picked up, she wouldn’t cling onto Jill or her husband, Bill. Carly had physical, cognitive and social delays and wasn’t reaching speech, reading and other development milestones experienced by children her age.

Jill and her family wished for everything to be okay.

“My husband kept saying you just worry too much, and I’m like ‘there’s something going on,’” says Dolan, a 52-year-old Powhatan County resident. “The first couple of years were really rough, just not having direction,” she recalls.

When she was about 9 months old, Carly started occupational therapy. She then began speech therapy as well at the family’s home. Jill says continued care through the Children’s Hospital Therapy Center in Midlothian made a world of difference for Carly’s development. 

“We were fortunate to start early intervention,” she says.

Dolan familyBeyond that early support, the family wanted answers on the root cause of Carly’s developmental delays. They met with a number of specialists. That journey led them to the Children’s Hospital of Richmond at VCU Genetics Department when Carly was 3 years old.

“We had a wonderful nurse practitioner at our pediatrician’s office who spent a lot of time with us for Carly’s 3-year wellness check. She sent us all over the place, to Neurology and all different departments,” Dolan says. “But she also sent us to Genetics even though there was no family history. They tested for seven or eight things.”

A blood test revealed Carly had Fragile X Syndrome. It’s a rare genetic disorder that can lead to the kind of developmental delays she was experiencing.

The National Fragile X Foundation says while the exact number of the people who have the disorder isn’t known, between 38,000 to 87,000 people in the U.S. could have Fragile X Syndrome. Research studies suggest that about 1 in 7,000 males have been diagnosed with the disorder as have 1 in 11,000 females, the foundation notes.

The condition involves a full mutation of a gene on the X chromosome, resulting in a wide range of different symptoms, the National Fragile X Foundation says. 

It can cause mild to more severe intellectual disabilities and can include autism, anxiety, learning disabilities, ADHD, poor eye contact and other symptoms, according to the foundation. It adds that females tend to have milder intellectual and behavioral symptoms than males.

Family members who are carriers of partial mutation of the gene can be impacted by other disorders, such as Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), a neurodegenerative disorder that can lead to tremors, balance, and cognitive issues.

Carriers can also be affected by Fragile X-Associated Primary Ovarian Insufficiency (FXPOI) that can affect fertility due to hormone issues.

The disorder is diagnosed more often in males, who have only one X chromosome, than in females, who have two X chromosomes, the foundation says.

Carly and her family’s journey with Fragile X

Despite learning of a new, life-altering condition affecting her young daughter, when VCU doctors told Jill and Bill of Carly’s diagnosis, Jill says they had a surprising feeling: relief.

At last, they had not just a name, but an explanation for what was happening to little Carly. Even though there’s no cure, having a name and a direction was reassuring, Jill says. Since Fragile X is a disorder that originates in a person’s chromosomes — the threadlike strands at the heart of human cells made of DNA carrying our genetic code — it can be inherited. So Carly’s family underwent testing following her diagnosis.

It involves a simple blood test that identifies a gene mutation that causes Fragile X. It’s more than 99 percent accurate, according to the National Fragile X Foundation.

In Jill’s case, the testing revealed Carly wasn’t the only one affected by Fragile X. The results showed Carly’s condition originated with Jill’s side of the family. Jill was a Fragile X carrier. That means she didn’t have the full X chromosome mutation that Carly does, but instead a “pre-mutation” in her genetic makeup which put her at risk for developing a Fragile X-related disorder.

Jill was eventually diagnosed with FXPOI that causes symptoms similar to early menopause.

She was then diagnosed in her late 40s with another carrier disorder, FXTAS, that would eventually lead her to care at the Parkinson’s and Movement Disorders Center.

It was the kind of discovery that often happens with family members after a child is diagnosed with Fragile X, says Stephanie Bissonnette, D.O., MPH, a VCU assistant professor of movement disorders who treats people with Fragile X and ataxia.

“We don’t often think about associated diagnoses like Fragile X-Associated Tremor/Ataxia Syndrome until a child has been diagnosed (with Fragile X Syndrome),” Bissonnette says. “But it may have been in the family for generations before that.”

That was the case with Jill’s family. Testing also revealed her father — Steve — was a Fragile X carrier just like Jill. He was then diagnosed with FXTAS when he was around 65 years old. 
“He showed no signs. But as you age, you are at higher risk for it,” Jill says. “And within a couple of years after learning he was a carrier, he started showing signs.”

The family got in touch with the National Fragile X Foundation, which led them to the MIND Institute at University of California Davis Health where top researchers have been working to unlock answers about Fragile X and associated disorders. The family started traveling to the West Coast to take part in research trials and studies and to receive treatment from Randi Hagerman, M.D., and her husband, Paul Hagerman, MD, Ph.D., the team who discovered the existence of FXTAS.

One email leads to PMDC — and home

Jill’s Fragile X-related ataxia affects her movement, memory, executive functioning and balance. She’s had at least one serious fall.

Ready to receive care close to home, she looked up the PMDC and sent an email directly to Director Brian Berman, M.D., M.S. She described her FXTAS diagnosis and how she had been out to the MIND clinic and had seen the Hagermans.

“(Berman) wrote back and said ‘I went to medical school with the Hagermans’ daughter,’” Jill says. “Dr. Paul Hagerman was also his professor.”

Berman also said there was someone on the PMDC team — Bissonnette — who was familiar with FXTAS and could treat Jill, who was thrilled to finally find a provider in her area who knew about her — and her family’s — condition.

Berman got Jill in contact with Bissonnette, who has a background in treating people with Fragile X and ataxia.

“It can be hard to find specialists who understand and treat ataxia,” Bissonnette notes. “Because ataxias are rare, it takes a long time to have seen enough patients to get the exposure and the comfort with treating these patients.”

The PMDC has about 50 patients with ataxias, a number that has been on the rise, Bissonnette says. She adds that the center hopes to eventually start a multidisciplinary clinic for those patients where they can get different treatments and therapies they need for their condition. 

Patients turned advocates to help families across Virginia and beyond

In addition to taking part in numerous studies that help researchers better understand their conditions, Jill, her father and Carly have all been to Capitol Hill on behalf of the National Fragile 
X Foundation to urge lawmakers to provide funding for research and to pass legislation that supports people like them who have rarely diagnosed disorders.

Carly’s first Capitol Hill event was actually a unique virtual experience in the COVID-19 era, when she spoke as a self-advocate for people with Fragile X.

“She’s always been very, very shy, which can be a part of Fragile X Syndrome and females,” Jill Dolan says. “And she just rocked it.”

Since then, Carly has participated at additional in-person advocacy events at the Virginia State Capitol in Richmond and on Capitol Hill in Washington, D.C.

Forging a new path spreading awareness of early detection and support

Jill advocates for more people to get a simple blood test that can uncover a Fragile X diagnosis, the kind of information that can be used to treat it earlier in families who may have no noticeable symptoms and no idea the disorder is in their genetic makeup.

Carly, meanwhile, is a member of the Young Adult Rare Representatives that supports youths who have rare disorders. And Carly has also shared her Fragile X experience with “Remember the Girls,” a group for females with X-linked disorders.

“Your disability should not define who you are as a person,” Carly wrote in a 2023 post for the group. “I wouldn’t be where I am today if I didn’t push myself outside of my comfort zone to try new things.”

Jill now has peace of mind that she’s able to be treated closer to home by Bissonnette, a provider with a background in treating ataxia and Fragile X-related health challenges.

“It just feels very uplifting and encouraging,” Dolan says. “It’s great to have someone to check in with who is knowledgeable about the most recent research and meds and therapies.”