Fragile X syndrome

What is fragile X syndrome?

Fragile X syndrome (FXS) is an inherited genetic disease passed down from parents to children that causes intellectual and developmental disabilities. It’s also known as Martin-Bell syndrome.

FXS is the most common hereditary cause of mental disability in boys. It affects 1 in 4,000 boys. It’s less common in girls, affecting about 1 in every 8,000. Boys usually have more severe symptoms than girls.

People with FXS usually experience a range of developmental and learning problems.

The disease is a chronic or lifelong condition. Only some people with FXS are able to live independently.

 

Fragile X syndrome (FXS) is a genetic disorder. A genetic disorder means that there are changes to the person’s genes. FXS is caused by changes in the fragile X mental retardation 1 (FMR1) gene. The FMR1 gene usually makes a protein called fragile X mental retardation protein (FMRP). FMRP is needed for normal brain development. People who have FXS do not make this protein. People who have other fragile X-associated disorders have changes in their FMR1 gene but usually make some of the protein.

FXS affects both males and females. However, females often have milder symptoms than males. The exact number of people who have FXS is unknown, but it has been estimated that about 1.4 per 10,000 males and 0.9 per 10,000 females have FXS.

 

What causes fragile X syndrome?

FXS is caused by a defect in the FMR1 gene located on the X chromosome. The X chromosome is one of two types of sex chromosomes. The other is the Y chromosome. Women have two X chromosomes while men have one X chromosome and one Y chromosome.

 

The defect, or mutation, on the FMR1 gene prevents the gene from properly making a protein called the fragile X mental retardation 1 protein. This protein plays a role in the functioning of the nervous system. The exact function of the protein is not fully understood. A lack or shortage of this protein causes the symptoms characteristic of FXS.

Fragile X Syndrome (Full Mutation)

Fragile X syndrome (FXS) is one of the most common causes of inherited intellectual disability. People who have FXS do not make the protein FMRP. In these people, the FMR1 gene has been turned off. Fragile X syndrome often results from a full mutation of the FMR1 gene.

Other Fragile X-Associated Disorders (Premutation)

People who have other fragile X-associated disorders (not FXS) have changes in their FMR1 gene but usually make some FMRP. In these people, the FMR1 gene is not turned completely off, but the gene does not function normally. Fragile X-associated disorders can be caused by a premutation of the FMR1 gene. People with a premutation of the FMR1 gene do not have FXS but may have another fragile X-associated disorder. Some people with a premutation may have noticeable symptoms, and others may not.

Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)

Fragile X-Associated Primary Ovarian Insufficiency (FXPOI) is a cause of infertility and early menopause among adult women. Women with a condition called primary ovarian insufficiency stop having menstrual cycles and have symptoms of menopause before 40 years of age. Women who have a premutation in their FMR1 gene are at higher risk for primary ovarian insufficiency and are at higher risk for having children who have FXS.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) is a disorder of the nervous system that can cause tremors and problems with walking, balance (also called ataxia), memory, and mood disorders among older adults. FXTAS can be caused by a premutation in the FMR1 gene.

What are the symptoms of fragile X syndrome?

FXS can cause learning disabilities, developmental delays, and social or behavioral problems. Disabilities vary in severity. Boys with FXS usually have some level of intellectual disability. Girls may have some intellectual disability or learning disability, or both, but many with fragile X syndrome will have normal intelligence. They might only be diagnosed with FXS if another family member is also diagnosed.

People with FXS may show a combination of the following symptoms as children and throughout life:

  • developmental delays, such as taking longer than normal to sit, walk, or talk compared with other children of the same age
  • stuttering
  • intellectual and learning disabilities, like having trouble learning new skills
  • general or social anxiety
  • autism
  • impulsiveness
  • attention difficulties
  • social issues, like not making eye contact with other people, disliking being touched, and trouble understanding body language
  • hyperactivity
  • seizures
  • depression
  • difficulty sleeping

Some people with FXS have physical abnormalities. These may include:

 

  • a large forehead or ears, with a prominent jaw
  • an elongated face
  • protruding ears, forehead, and chin
  • loose or flexible joints
  • flat feet

Signs and Symptoms

Signs that a child might have FXS include:

·         Developmental delays (not sitting, walking, or talking at the same time as other children the same age);

·         Learning disabilities (trouble learning new skills); and

·         Social and behavior problems (such as not making eye contact, anxiety, trouble paying attention, hand flapping, acting and speaking without thinking, and being very active).

 

Males who have FXS usually have some degree of intellectual disability pdf icon[280 KB / 2 pages]that can range from mild to severe. Females with FXS can have normal intelligence or some degree of intellectual disability. Autism spectrum disorders (ASDs) also occur more frequently in people with FXS.

 

What is early intervention?

Early intervention is a system of services that helps babies and toddlers with developmental delays or disabilities. Early intervention focuses on helping eligible babies and toddlers learn the basic and brand-new skills that typically develop during the first three years of life, such as:

·         physical (reaching, rolling, crawling, and walking);

·         cognitive (thinking, learning, solving problems);

·         communication (talking, listening, understanding);

·         social/emotional (playing, feeling secure and happy); and

·         self-help (eating, dressing).

Examples of early intervention services | If an infant or toddler has a disability or a developmental delay in one or more of these developmental areas, that child will likely be eligible for early intervention services. Those services will be tailored to meet the child’s individual needs and may include:

·         Assistive technology (devices a child might need)

·         Audiology or hearing services

·         Speech and language services

·         Counseling and training for a family

·         Medical services

·         Nursing services

·         Nutrition services

·         Occupational therapy

·         Physical therapy

·         Psychological services

Services may also be provided to address the needs and priorities of the child’s family. Family-directed services are meant to help family members understand the special needs of their child and how to enhance his or her development.

 

Authorized by law | Early intervention is available in every state and territory of the United States. The Individuals with Disabilities Education Act (IDEA) requires it–Part C of IDEA, to be precise. That’s why you’ll sometimes hear early intervention referred to as Part C.

How is fragile X syndrome diagnosed?

Children who show signs of developmental delays or other outward symptoms of FXS, such as a large head circumference or subtle differences in facial features at a young age, may be tested for FXS. Your child may also be tested if there’s a family history of FXS.

The average age of diagnosis in boys is 35 to 37 months. In girls, the average age of diagnosis is 41.6 months.

 

FXS can be diagnosed using a DNA blood test called the FMR1 DNA test. The test looks for changes in the FMR1 gene that are associated with FXS. Depending on the results, your doctor may choose to do additional testing to determine the severity of the condition.

 

FXS can be diagnosed by testing a person’s DNA from a blood test. A doctor or genetic counselor can order the test. Testing also can be done to find changes in the FMR1 gene that can lead to fragile X-associated disorders.

A diagnosis of FXS can be helpful to the family because it can provide a reason for a child’s intellectual disabilities and behavior problems. This allows the family and other caregivers to learn more about the disorder and manage care so that the child can reach his or her full potential. However, the results of DNA tests can affect other family members and raise many issues. So, anyone who is thinking about FXS testing should consider having genetic counseling prior to getting tested.

 

Uncover the Facts: Fragile X Myth Busters for families and health professionals.

How is fragile X syndrome treated?

FXS cannot be cured. Treatment is aimed at helping people with the condition learn key language and social skills. This may involve receiving extra help from teachers, therapists, family members, doctors, and coaches.

There may be services and other resources available in your community to help children learn important skills for proper development. If you’re in the United States, you can contact the National Fragile X Foundation at 800-688-8765 for more information regarding specialized therapy and educational plans.

Medications that are typically prescribed for behavior disorders, like attention deficit disorder (ADD) or anxiety, may be prescribed to treat the symptoms of FXS. Medications include:

 

  • methylphenidate (Ritalin)
  • guanfacine (Intuniv)
  • clonidine (Catapres)
  • selective serotonin reuptake inhibitor (SSRI), such as sertraline (Zoloft), escitalopram (Lexapro), duloxetine (Cymbalta), and paroxetine (Pail, Pexeva)

Treatments

There is no cure for FXS. However, treatment services can help people learn important skills. Services can include therapy to learn to talk, walk, and interact with others. In addition, medicine can be used to help control some issues, such as behavior problems. To develop the best treatment plan, people with FXS, parents, and health care providers should work closely with one another, and with everyone involved in treatment and support—which may include teachers, childcare providers, coaches, therapists, and other family members. Taking advantage of all the resources available will help guide success.

Early Intervention Services

Early intervention services help children from birth to 3 years old (36 months) learn important skills. These services may improve a child’s development. Even if the child has not been diagnosed with FXS, he or she may be eligible for services. These services are provided through an early intervention system in each state. Through this system, you can ask for an evaluation. In addition, treatment for particular symptoms, such as speech therapy for language delays, often does not need to wait for a formal diagnosis. While early intervention is extremely important, treatment services at any age can be helpful.

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