Children's Hospital Colorado

Fragile X Syndrome

What is fragile X syndrome? 

There is much variability in the severity and symptoms in fragile X, however the majority of males have intellectual disability and approximately 30 to 60% have autism spectrum disorders or autistic behaviors. Females with fragile X often have learning disabilities, and approximately 30% of females have intellectual disability. Fragile X syndrome is the most common inherited cause of intellectual disability and one of the most common genetic disorders associated with autism. The signs and symptoms of fragile X syndrome can vary between individuals, and symptoms in males are usually more significant than in females. The syndrome occurs in approximately 1 in 3,600 males and 1 in 4,000-6,000 females.

Early delays in speech and motor development are common in infants and toddlers of both sexes. Other common behavioral and emotional characteristics can include attention-deficit/hyperactivity and impulsivity (ADHD), anxiety, hand flapping, poor eye contact, temper tantrums and sensitivities to touch and sounds.

What causes fragile X and who gets it?

Fragile X syndrome is caused by a change or mutation in a gene on the X chromosome called the FMR-1 (fragile X mental retardation-1) gene. Chromosomes are made up of thousands of genes that are passed from generation to generation. Most individuals have 46 chromosomes,two of which are sex chromosomes. In males, the sex chromosomes are X and Y. In females there are two Xs. 

Each gene of a chromosome contains a specific code of DNA that determines the function of the gene in the body. The FMR-1 gene produces a protein called FMRP, which plays an important role in brain development and in the biological mechanisms involved in learning and memory.

A mutation in the FMR-1 gene causes fragile X syndrome by making the body unable to produce the FMRP protein. The lack of the FMRP protein causes fragile X syndrome.

Since males have only one X chromosome, if they have the fragile X mutation they will produce minimal or no FMRP. Females have two X chromosomes,so if they have the mutation on one of their X chromosomes, the other X chromosome still produces normal levels of FMRP in about half the cells of the body. This explains why males with fragile X syndrome are usually more affected than females.

What are the signs and symptoms of fragile X syndrome?

Early delays in speech and motor development are usually the earliest symptoms in children with fragile X. Some common physical and medical features include a long face, prominent chin, high-arched palate, large and prominent ears, low muscle tone and large testicles in males during puberty.

Connective tissue problems may include double-jointed fingers, hyperextensible joints, flat feet, mitral valve prolapse, constipation and recurrent ear infections. Seizures occur in approximately 15 to 20% of children with fragile X syndrome. Sleep problems are also very common.

How do symptoms differ in girls?

Symptoms of fragile X in females are usually milder compared to males, although some females with fragile X syndrome can have severe symptoms. In about two-thirds of cases, females have mild or moderate learning disabilities, while one-third of females have intellectual disability. Behavioral difficulties in females can also include inattention, anxiety and sensory sensitivities. F can also share the physical features seen in males with fragile X, although the features are typically less prominent in females.

What tests are used to diagnose fragile X syndrome?

In order to identify fragile X syndrome, doctors will take a sample of your child's DNA, which is usually done through a blood test. That sample is sent to a lab for testing to identify if there is a genetic mutation in the FMR-1 gene's DNA.

This blood test can also tell if someone has a premutation in their FMR-1 gene. If so, that person is a carrier for fragile X syndrome who may pass it on to their own children.

How is fragile X syndrome treated?

Throughout childhood, ongoing therapies and support to address learning and intellectual disabilities, speech disorders, gross and fine motor deficits, anxiety and other behavioral and emotional difficulties may be necessary. Counseling and medications are often recommended to help children with behavioral, emotional or social issues.

The treatment of fragile X syndrome depends on each particular child's needs. In most cases, treatment involves strong early intervention therapies to address developmental delays, including speech, occupational and physical therapies. Specific therapies for autism spectrum disorders may also be recommended, if needed.

About 15% of individuals with fragile X also have seizures that are treated with medications by a neurologist. Screening and treatment of seizures and other associated medical problems are also important to optimize development and behavior, such as treatment of ear infections (to ensure adequate hearing for speech development), sleep disorders, sensory-based feeding difficulties, constipation and others.

There are also many new medications that have been developed specifically for fragile X syndrome that target the underlying neurobiological differences caused by the fragile X mutation and missing FMRP protein. These medications are currently being studied in Colorado and around the country.

Why choose Children's Hospital Colorado for your child's fragile X syndrome?

The Fragile X Clinic at the Children's Colorado treats children, young adults and families affected by mutations in the fragile X gene. Our professionals have experience evaluating and treating individuals with fragile X syndrome and fragile X permutations. Members of the Fragile X Clinic team at Children's Colorado include developmental pediatricians, a genetic counselor and a clinical psychologist.

Consultation with other departments at Children's Colorado including Clinical Genetics, Hearing, Speech and Learning, Occupational Therapy, Physical Therapy, Neurology, Psychiatry, Sleep Medicine, and Dentistry are available when our patients need them. We also have close collaborations with adult neurologists at University of Colorado Hospital and many community providers who have expertise in the treatment of fragile X and fragile X related conditions.

What to expect from the Fragile X Clinic

After a clinical evaluation, families receive a comprehensive report that details specific recommendations for your child in order to support their developmental, behavioral, academic and emotional needs, as well as necessary medical management. Ongoing developmental monitoring, medication management for behavioral difficulties and general consultation about updates in clinical care and research in fragile X disorders are also available through the clinic.

Our fragile X research

The Fragile X Clinic within the Developmental Pediatrics Program is one of 26 clinics nationwide in the Fragile X Clinical and Research Consortium sponsored by the National Fragile X Foundation. Clinics in the consortium provide individuals and families affected by fragile X-associated disorders with evaluation and care supported by the latest medical, educational and research knowledge available.

The consortium is actively establishing "best practice" recommendations for evaluation and ongoing care in fragile X, enrolling fragile X families into a national registry to be used for research, and research recruitment, and building a nationwide network for collaborative research efforts.

For more information or to make an appointment, please call 720-777-8361.

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