Children & Adolescents Clinic

 Home Parent's Guide

Clinical Reference Systems: Pediatric Advisor 10.0

Fragile X Syndrome

Description

Fragile X syndrome is an inherited disorder caused by a mutation (a change in the genetic information) of a specific gene.

Fragile X syndrome can cause hyperactivity, learning problems, and emotional problems. It can also cause mental retardation, although some children with fragile X have normal IQs. This disorder is the most common known cause of inherited mental retardation.

Cause

Fragile X syndrome is a genetic disorder. The parents or other family members did not do anything to cause it. The gene mutation has usually been carried unknowingly for many generations. Both males and female carriers can have a small fragile X mutation (called a premutation) and still be completely normal. The premutation can expand to a larger full mutation when it is passed on to the next generation through a female. It is the full mutation that causes fragile X syndrome. Your child may be the first one in your family with behavior or development problems, or there may be other relatives who are affected by the fragile X mutation. Your doctor or a genetic counselor will explain how this gene mutation is passed on in your family and who should be tested for it.

The characteristic problems of fragile X syndrome are caused by the full mutation of a specific gene called the fragile X mental retardation 1 gene (FMR1). Genes are the building blocks of chromosomes. Each person has 23 pairs of chromosomes. One pair, called the sex or X and Y chromosomes, determine whether a person is male or female. Females have two X chromosomes and males have one X and one Y chromosome. In fragile X syndrome the gene mutation is on an X chromosome.

The full mutation in the FMR1 gene causes the FMR1 gene to turn off. Therefore, the normal message for building a special protein from this gene is missing, and the lack of this protein is the cause of the developmental and behavioral problems in fragile X syndrome.

Usually boys are affected more severely than girls because the FMR1 gene is on the X chromosome and boys have only one X chromosome. Because a girl has two X chromosomes, her second X chromosome usually does not contain the mutation and therefore helps suppress the problems caused by the mutation on the other X chromosome.

Physical, Behavioral, and Health Concerns

  1. Physical characteristics

    Boys affected by fragile X syndrome often have prominent ears, a large head, a prominent forehead, extra flexible finger joints, a high palate, soft skin, and flat feet. During puberty, boys usually develop large testicles (called macroorchidism) and a somewhat long face. Many of these features are seen in the general population so most of these boys look normal even though they have features of fragile X syndrome.

    Girls may also have physical features associated with fragile X syndrome, particularly large or prominent ears, very flexible finger joints, and flat feet.

  2. Health concerns

    In general, children with fragile X syndrome do not have a lot of medical complications. The health problems they may have include:

    • frequent ear infections
    • seizures (occur in about 20% of children with fragile X)
    • strabismus, which is a weak eye muscle and occurs in about 30% of children with fragile X
    • mitral valve prolapse, a heart valve problem, which occurs in about 50% of adults with fragile X
    • rarely, a hernia or joint dislocation.

  3. Behavioral characteristics

    The major problems associated with fragile X syndrome involve behavior and slow development leading to a lower IQ. The majority of girls with fragile X syndrome show learning problems and a short attention span along with shyness, social anxiety, and moodiness. Approximately 30% of girls with fragile X syndrome are mentally retarded. The majority of males with fragile X syndrome are mentally retarded, meaning that their IQs are below 70.

    Children with fragile X are usually extra sensitive to stimuli in their environment, such as noises or changes in their routine. They are usually anxious and have frequent tantrums.

    For most boys and some girls with fragile X, the activity level is high and the attention span is short. Language development is especially slow. Most boys do not talk much by age 3. Unusual behaviors, sometimes termed autisticlike behaviors, commonly develop by 3 years of age. Some of these behaviors are hand flapping, hand biting, poor eye contact, excessive chewing on clothes, and pulling away from touch. These children may ask questions over and over again even after hearing the answer.

  4. Strengths of children with fragile X

    Children with fragile X syndrome have many strengths, including their social abilities (although shyness is common); a wonderful sense of humor; an excellent memory for people, events, and directions; intense interests; and outstanding imitation skills.

Treatment

There is no cure for fragile X syndrome, but many treatments are available.

  1. Therapy

    If your child is diagnosed in infancy, your doctor will discuss infant stimulation programs. Developmental preschool programs are helpful for children under 5 years.

    Speech, language, occupational, and physical therapy are important to optimize motor skills and language development. A sensory integration type of occupational therapy can be helpful for behavioral problems. The occupational therapist will demonstrate physical calming techniques, such as deep pressure back rubs and joint compression, which may help to calm behavior outbursts or tantrums at home.

    Your doctor or psychologist can help you establish a behavior program at home that includes consistent structure, regular routines, and positive feedback.

  2. Education

    Your child's special education program in school should include participation in regular education whenever possible, individualized help to modify assignments and tutor weak academic areas, speech and language therapy, occupational therapy, and computers. Your doctor can help you obtain these services and appropriate therapy when needed.

  3. Medical care and medications

    Your doctor will treat the medical problems that may occur in a child with fragile X syndrome.

    Your doctor may prescribe medications that can improve poor attention span, hyperactivity, tantrums, aggression, anxiety, obsessive thinking, or other behavioral or emotional difficulties. Medication may work with other methods of treatment to improve your child's learning and behavior. Your doctor will tell you about the side effects of any medication that is recommended. Such medications are used for a trial period and are continued only if they are found to be helpful. If your child has an adverse response to medication, you should call your doctor and discuss the response.

Genetic Tests

There are two types of blood tests for fragile X syndrome. One is the chromosome, or cytogenetic, test, which can show the break in the X chromosome. The second is a newer DNA test that is more exact and less expensive.

Because fragile X syndrome is a genetic disorder, you should consider this during future pregnancies. Prenatal diagnosis and new reproductive technologies should be discussed with your genetic counselor.

Parent Support Groups

When the diagnosis of fragile X syndrome is made for your child, it is often helpful to talk to another family with a child who is similarly affected. The National Fragile X Foundation, at 1-800-688-8765 or (303) 333-6155, has a list of resource centers and parent support groups. It is helpful to call them directly for educational information and the phone number of a parent nearest you.

Remember, children with fragile X syndrome are difficult to raise, and parents need to have personal time and recovery time on a regular basis. If you as parents feel overwhelmed, depressed, or excessively anxious, discuss this with your doctor. He or she can help you. When you as parents are healthy, you can better help your child reach his or her optimal potential.


Written by Randi Hagerman, M.D., Developmental Pediatrics, The Children's Hospital, Denver, CO
Copyright 1999 Clinical Reference Systems