Something was wrong with Brayson Thibodeaux. At 15 months old, he still was not walking; his parents and grandparents were certain that his development was slower than normal. After pushing doctors for answers they finally got him to a neurologist who recommended a genetic test. Brayson had fragile X syndrome, the leading heritable cause of intellectual disability and of autism.
The discovery sent ripples through the extended family, who live outside New Orleans. Brayson’s great-grandmother, Cheryl, recalled having heard of fragile X and discovered a cousin whose grandson had the same condition. She soon learned that many members of her family were confirmed carriers of a genetic condition—the fragile X pre-mutation—that put them at risk of having children with this syndrome.
“Fragile X” refers to a mutation that alters the X chromosome in such a way that, viewed under a microscope, it would look like a piece was about to break off. That is because one gene contains multiple repetitions of noncoding DNA—specifically CGG (cytosine, guanine, guanine). The exact number of CGG repetitions is variable, but when it reaches more than 200, it is considered to be the full mutation, which causes the syndrome. People with between 55 and 200 repeats are said to have a partial or pre-mutation, an unstable gene that can expand into the full mutation in future generations.
Doctors once thought the pre-mutation was benign but more recent research shows that it puts carriers at risk of developing a number of health problems. These include a neurodegenerative disorder called fragile X–associated tremor/ataxia syndrome (FXTAS) that primarily affects men, and, in women, a condition called fragile X–associated primary ovarian insufficiency (FXPOI), a leading cause of infertility and premature menopause. Carriers also face an increased risk of anxiety and mood disorders.
Members of Brayson and Cheryl’s family have experienced all of the above. To help scientists discover more about the fragile X gene, Brayson, his mother and brother are participating in a clinical study that will track the boy’s development. The family is also eager to increase awareness among the general public and were willing to share their stories with Scientific American MIND.
Below we present seven family members, each afflicted in a different way. “It’s a very tough situation, dealing with fragile X,” says Brayson’s mother, Alyssa. “But if you have good support—which I do, I have my entire family on my side and fighting with me every day—you can get through it easier.”
Brayson Thibodeaux, age 2
—has Fragile X syndrome
By the time Brayson was one year old, his family was deeply concerned about his physical and cognitive development. Their pediatrician advised patience but as his grandmother, Chrystie Shubert, says, “When you sit in front of your kids every day and watch them, you know when something’s wrong.”
Noticing the way he would try to walk on his toes, they brought him to an orthopedist, who in turn sent them to a neurologist. After he reached 15 months and was still clearly lagging in development the doctor ordered a genetic test and the family discovered that Brayson had fragile X syndrome, a disorder that causes cognitive impairment (often including autism) and learning disabilities as well as physical traits such as an elongated face, prominent ears and low muscle tone.
The news was devastating to his mother, Alyssa, who had recently given birth to a second child and was experiencing postpartum depression. But in the past year she has come to accept her role as Brayson’s voice and advocate. Despite his challenges, she reports, “he’s overachieved on many things we didn’t think he was going to be able to do.”
Bowen Thibodeaux, 1
—awaiting test results
Whether or not the younger Thibodeaux sibling has fragile X syndrome is still unclear. He appears to be less developmentally delayed than his older brother, Brayson, was at age one. He crawls and says “mama” and “dada.” Yet one round of genetic testing suggests he has the same syndrome.
Given the differences between the boys, Bowen’s mother Alyssa is eager to have him retested. She hopes to learn more from testing that is part of an ongoing clinical study, which will track both children’s development over time.
Alyssa Shubert, 21
—either a full or pre-mutation carrier
After the shock of discovering her son had fragile X syndrome Alyssa and her family began to learn more about the condition with help from Louise Gane, a genetic counselor. As the mother of a child with the syndrome, Alyssa carries the fragile X pre-mutation or possibly the full fragile X mutation—the impact of which is often muted in women because they have a second, healthy X chromosome.
While learning about conditions related to fragile X, she had an epiphany. “It straight up explains my whole life,” she says. She had been diagnosed with ADHD and has dealt with serious anxiety for years. In school she struggled to keep up. “I could study all night long and then when I got to a test, I would just blank out,” she says. She also had endometriosis, a uterine disorder, and her doctors predicted that she would have difficulty conceiving. All of these conditions have been linked to the fragile X pre-mutation.
Chrystie Shubert, 39
For Chrystie, learning about the effects of carrying an abnormal fragile X gene explained a lot. She has two children, born 14 years apart. The gap is not the result of planning but simply, as she puts it, because “it didn’t happen” sooner. One possibility is that as a carrier her reproductive health was compromised.
Similarly, she wonders if her daughter Alyssa’s academic struggles can be attributed to the mutated gene. “I never knew to have her tested,” Chrystie says. “If I’d known about it a long time ago, maybe she could have had more help.”
Braden Shubert, 7
—anger issues could indicate pre-mutation
Braden is Chrystie’s son (and Alyssa’s brother). As a baby he suffered from night terrors and now as a child he exhibits anger issues including fighting with his mother. Although a genetic counselor suggested that the latter behavior might relate to carrying the pre-mutation, genetic testing indicates he is not a carrier. Unconvinced, the family hopes another test will bring greater clarity.
Michele Hansen, 33
—confirmed FXPOI carrier
Michele and her husband had been trying to conceive when they learned about Brayson’s diagnosis. At the time, she was aware that a condition called endometriosis, involving misplaced uterine tissue, could make it difficult for her to become pregnant. But she soon discovered another obstacle to conception—she had FXPOI.
But Michele and her husband are not giving up hope. In meeting others affected by fragile X they discovered a woman with FXPOI who lives just 10 minutes away and had a successful pregnancy after seven years of trying.
Michele and her husband have continued to pursue multiple treatment options. She knows that if they succeed, their children have a 50 percent risk of inheriting the mutated X chromosome. Although that possibility does not alter their desire to have kids, they plan to use amniocentesis to assess whether or not their baby has fragile X syndrome, so that they can be more prepared as parents. It helps, too, to be part of a supportive family that has grown even more tight-knit after learning about their shared genetic risks. “I think it has brought all of us closer,” she says. “We all have a lot more help from each other, we all pitch in.”
Cheryl Davidson, 60
When Cheryl discovered that her great-grandson had fragile X syndrome, she looked for more answers in her extended family. She discovered, for instance, that several of her first cousins were confirmed carriers and one had FXTAS. She suspects that one of her siblings, since deceased, may have also had this neurodegenerative disorder, which is marked by tremor and behavioral changes.
Her investigation has led her to develop a family tree that offers hints as to how the pre-mutation passed from one generation to the next. Given the fact that her affected cousins are on her father’s side of the family and that she herself has a daughter with a fragile X–associated condition, it is probable that both her father and uncle carried the pre-mutation. And because the condition is linked to the X chromosome, which males receive from their mothers, it is also likely that her grandmother Mary was a carrier.
Although she herself has not been tested—“my childbearing years are over,” she explains—Cheryl urges people to consider genetic screening. “If you know that it’s in your family, please be tested and find out for sure.”