Fragile X Treatment and Research Center

The Fragile X Treatment and Research Center at Children's Hospital Colorado is a unique specialty clinic for children and their families affected with Fragile X syndrome.

Children and their parents have the opportunity to meet with professionals who have significant experience with Fragile X syndrome, including a developmental pediatrician, genetic counselor and clinical psychologist. Referrals for speech therapy, occupational therapy, physical therapy, neurology and all other medical specialties are available as needed. After a clinical evaluation, the family receives a comprehensive report detailing specific recommendations for the child and family based on their assessment in order to support the child's development, academic, and emotional needs, as well as necessary medical management.

What are the signs and symptoms of Fragile X syndrome?

Fragile X syndrome is the most common cause of inherited intellectual disability. A family history of Fragile X syndrome or intellectual disability may be the initial indication for testing an individual for Fragile X syndrome. Fragile X can affect both males and females, although males tend to be more severely and commonly affected since the inherited gene is on the X-chromosome.

Individuals with Fragile X syndrome can have the following symptoms:

• Longer faces with large and protruding ears
• Flat feet, a high arched palate (roof of the mouth), double-jointed fingers and hyper-flexible joints (these features are not present in all individuals with Fragile X)
• Developmental delays, learning or intellectual disabilities and behavioral difficulties, including hyperarousal, attention problems, hyperactivity, impulsivity, autism spectrum disorders, social anxiety, sensory disorders and aggression
• Seizures, recurrent ear infections and sleep disorders

Individuals who are carriers of Fragile X (having the premutation in the FMR1 gene) may have these symptoms:

• Tremors, ataxia, neuropathy, dementia, premature menopause, autoimmune diseases, thyroid abnormalities, migraine headaches, anxiety, depression, ADHD, sensory disorders, speech delays and learning disabilities

Carriers are at risk for having children and/or grandchildren with Fragile X syndrome, since the gene mutation can expand from generation to generation.

How is Fragile X syndrome diagnosed?

Fragile X syndrome is diagnosed by a DNA test of the FMR1 gene, which is located on the X-chromosome. This test determines the number of "CGG" repeats within the FMR1 gene. Results of 200 or more "CGG" repeats (also known as a full mutation) confirm a diagnosis of Fragile X syndrome.

The full mutation causes the FMR1 gene to turn off and in turn make no protein. Results of less than 200 "CGG" repeats, but more than 54 repeats, confirm a diagnosis of a carrier of Fragile X (also known as a premutation). The premutation causes the FMR1 gene to remain "on" however it is at risk for expanding the number of "CGG" repeats in future generations. Results with 45-54 repeats are considered the "grey zone" (unknown significance). Results with less than 45 repeats are considered normal.

The Fragile X gene can expand when passed on from mother to child (a process called "anticipation"). Therefore a carrier mother is at risk for having a child with a full mutation=Fragile X syndrome. While males and females can both be affected by Fragile X syndrome, typically females are less severely affected since the FMR1 gene is on the X-chromosome and females have two X-chromosomes, and therefore two copies of the FMR1 gene. In females, the other x-chromosome typically carries a normal functioning FMR1 gene. Males have only one X-chromosome, and therefore only have the one copy of the FMR1 gene.

Treatment options

The treatment for Fragile X syndrome should address the particular child's needs, such as learning disabilities, anxiety, social deficits, speech delays and sensory disorders.

Treatment typically involves interventions including:

• Speech and occupational therapies
• Special education
• Counseling and/or medications may be recommended to help children with behavioral, emotional or social issues.
• Medication is also commonly used for health related problems such as seizures, recurrent ear and sinus infections and GI problems. 

Who gets Fragile X syndrome, and can it be prevented?

Fragile X syndrome affects approximately 1/4000 males and 1/8000 females. It is the most common cause of inherited intellectual disability, and caused by the "CGG" expansion in the FMR1 gene located on the X-chromosome. As an X-linked disorder, males tend to be more severely affected than females, although both genders can be affected.

Fragile X mutations have "anticipation" in which the "CGG" repeat within the gene can expand when passed from mother to child. Therefore a mother can be an asymptomatic carrier of Fragile X and have a child affected with Fragile X syndrome. Each child of a carrier mother has a 50% chance of inheriting the Fragile X mutation.

Anticipation does not typically occur when the Fragile X mutation is passed from father to child. Sons of carrier fathers will not inherit the Fragile X mutation (they inherit the Y chromosome not the X chromosome from their father). All daughters of a carrier father will inherit the Fragile X mutation (they inherit the X chromosome from their father), however the "CGG" repeat number typically is the same size as seen in the father's gene.

When should I seek medical attention?

Children with Fragile X syndrome can benefit from early interventions for speech delays, motor delays, learning disabilities, behavioral issues and/or social deficits. Therefore, it is highly recommended that children with Fragile X syndrome be seen for a developmental, psychological and medical evaluation shortly after receiving a diagnosis and close monitoring of development be followed closely throughout childhood.

Children, adolescents and adults with Fragile X syndrome should also seek further evaluation if there are difficulties with behavior, anxiety, attention or sensory sensitivities, since there are many treatments in Fragile X syndrome that are helpful for these disorders.

For more information or to set up an appointment, please contact the Genetic Counselor and Fragile X Clinic Coordinator, Susan Howell at (720) 777-8361.

Research opportunities

There is a lot of ongoing research in the field of Fragile X. Many targeted treatments are currently being developed and are being tested in clinical trials at our center and at other centers around the world. Dr. Nicole Tartaglia is the Fragile X Clinic Director and she participates in several ongoing research projects in Fragile X Syndrome. For more information about her current and ongoing Fragile X studies, please contact Susan Howell at 720-777-8361.

Additional Fragile X syndrome resources

National Fragile X Foundation

FRAXA Research Foundation

Colorado Fragile X LINKS Group