What is Fragile X Syndrome?

Fragile X Syndrome (FXS) is a genetic disorder in which the FMR1 gene does not produce an important protein that is key to brain development. There is no cure, and those with the syndrome typically experience developmental delays and behavioral issues. FXS is a spectrum of disorders that includes the distinct types called grey zone, premutation, and full mutation, The type is determined by how it is passed down to each generation in the family.

Robyn Filipink, MD, is director of the Movement Disorders Clinic, the Tourette Syndrome Clinic, and the Fragile X Center at UPMC Children’s Hospital of Pittsburgh. She is a clinical associate professor in the Department of Pediatrics at the University of Pittsburgh School of Medicine. Dr. Filipink is board certified in Pediatrics and Neurology with special qualifications in Child Neurology and Neurodevelopmental Disabilities.

Dr. Filipink says with early diagnosis and the right support, those with FXS can lead full lives.

Signs and Symptoms of Fragile X Syndrome

The earliest signs of FXS are developmental delays. These delays often are related to speech or motor skills. Children might walk later or miss milestones for crawling or talking. Many with the syndrome experience learning difficulties. Some exhibit hand flapping or lack of eye contact.

Dr. Filipink says some with the syndrome have a dysmorphic face that is recognizable as well. These features might include a long face, large ears and a prominent jaw or forehead. Some also have flat feet and generalized low tone called hypotonia.

About 40 percent of those with FXS will also be diagnosed with autism spectrum disorder (ASD). For that reason, the Academy of Pediatrics recommends that anyone with ASD be tested for FXS. Because those with ASD are typically diagnosed between 18 months and 2.5 years of age, Dr. Filipink says this diagnosis can be made early. The sooner ASD is identified, the sooner interventions and therapies can begin.

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Diagnosis of FXS

Those with FXS are typically diagnosed in childhood. Rarely, adults will be diagnosed because another family member is diagnosed first.

Additionally, genetic testing has progressed to allow for early diagnosis of the syndrome.

“There’s more genetic testing that’s done prenatally, so now there are some families who will have a prenatal diagnosis,” Dr. Filipink says.

Otherwise, patients are typically diagnosed between ages 2 and 7 when they present for evaluation of developmental delays or behavioral issues.

“The goal is earlier identification so that beneficial interventions, such as therapies, can be started as soon as possible. Autism can be screened, and families can gain a better understanding of the lifetime medical complexities for their child,” she says.

Prognosis of FXS

The prognosis for full mutation FXS differs among the sexes. Because it affects the X chromosome, women can have a range of symptoms from learning disabilities and ASD to no symptoms.

Men, however, will almost always have an intellectual disability — typically an IQ in the 70s — and 40 percent will have ASD as well, Dr. Filipink says. Some children go on to have ADHD, anxiety, and aggression as well.

A common risk for adults with FXS is a sedentary lifestyle, Dr. Filipink says, although there is not a direct correlation between the disease and the quality of life.

“There’s not an associated decreased life expectancy but the life expectancy could be changed because of the sedentary lifestyle that occurs for a person having intellectual disability and autism,” she says.

Additionally, if families have access to the proper support and can get individuals involved in therapy and social groups, Dr. Filipink says quality of life can be good.

Treatment for FXS

There is no cure for FXS, but Dr. Filipink says that therapies, medications, and social groups can help to improve behavioral issues and help improve quality of life. Specifically, physical therapy can help with motor skills and speech therapy can help with communication skills.

Dr. Filipink says early intervention is key to improving quality of life if a child can gain access to those services at a formative age.

Complications of FXS

FXS is known as a triple repeat disorder which runs in families. Parents can be carriers of the disease, which presents differently in each generation.

“It’s a very microscopic change in the genetic material on the X chromosome,” Dr. Filipink says. “And when it’s passed on to each generation, if a female passes that on, that area of repeat grows, and so that child will have more symptoms.”

Dr. Filipink explains that older generations within the family with a premutation might show signs of a neurodegenerative disorder in their later years. Mothers of children with a full FXS mutation may have a range of symptoms and commonly experience anxiety and learning issues. A child who is diagnosed with full mutation FXS typically presents with global developmental delays, which is more easily recognized as a symptom.

“We see that moms themselves can have thyroid disease, learning disabilities, or anxiety, and then we see their parent may have something that develops over time, which is a neurodegenerative disorder,” Dr. Filipink says.

“Sometimes the females in the family with Fragile X premutation can have fertility issues because they have something called FXPOI or ovarian insufficiency syndrome. ”

Women with FXPOI experience irregular periods and reduced function in their ovaries.

In short, the symptoms differ greatly from one generation to the next, and it’s not often clear that these symptoms are linked to the syndrome until a younger person in the family with a full mutation is diagnosed. Overall, each successive generation usually carries more symptoms.

UPMC Children’s Work on FXS

FXS runs in families and a child’s diagnosis can be the key to unlocking treatments and resources for other affected family members with related symptoms.

Mothers of children with FXS typically have high anxiety and therefore, Dr. Filipink says, the Fragile X Center at UPMC Children’s Hospital offers support with scheduling appointments and mentally and emotionally preparing parents for what to expect during their clinic appointment.

As director of the Movement Disorders Clinic, the Tourette Syndrome Clinic, and the Fragile X Center at UPMC Children’s, Dr. Filipink treats about six to eight patients each month with the spectrum of Fragile X: grey zone, premutation, and full mutation. Patients range in age from birth to late adulthood.

The Fragile X Center not only provides initial assessments and education regarding this genetic syndrome, but also follows and treats individuals and their affected family members through their lifetimes. The Center connects patients and their families to local resources in their community, including other medical specialists, therapies, behavioral health, school supports, transitional care, and financial planning.

Dr. Filipink reports that the Center recently completed a national drug trial for young children with FXS looking at the possible effects on speech development, learning, and behaviors. In Fall 2022, the Center will start a new research study focusing on following developmental and behavioral outcomes for children and young adults with FXS.

To learn more, please visit The Fragile X Center.

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