Fragile X Syndrome

What is fragile X syndrome?

Fragile X syndrome is an inherited disorder. It can cause hyperactivity, learning problems, and emotional problems. It can also cause mental retardation and autism. Some children with fragile X have normal IQs. This disorder is the most common known cause of inherited mental retardation and affects both males and females.

What is the cause?

Fragile X syndrome is a genetic disorder caused by a mutation (a change in the genetic information) of a specific gene. 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 have a normal IQ. 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 health care provider 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 not having enough of this protein causes 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.

What are the 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 usually have features of fragile X syndrome.

   Girls may also have physical features associated with fragile X syndrome, particularly large or prominent ears, 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 and adults with fragile X)
   • strabismus, a weak eye muscle, occurs in some 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 and the majority have significant learning disabilities. 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 autistic-like 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.

   Approximately 20% to 35% of children with fragile X have autism. An additional 15% to 20% have pervasive developmental disorder (PDD-NOS), which has some of the same symptoms as autism. Children with autism have trouble with social interaction, language, and repetitive or ritualistic behavior.

   Irritability and moodiness are a problem for most people with fragile X. Moodiness combined with anxiety leads to aggressive behavior in about one-third of adolescent boys and men with fragile X.

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.

What is the treatment?

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

1. Therapy

   If your child is diagnosed in infancy, your provider 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 provider or psychologist can help you establish a behavior program at home that includes consistent structure, regular routines, and positive feedback.

   If your child has autism and fragile X syndrome, then an applied behavioral analysis (ABA) or similar program would probably be helpful as well.

2. Education

   Your child's special education program in school should include participation in regular education whenever possible. Your child should also have individualized help to modify assignments and tutor weak academic areas. Speech and language therapy, occupational therapy, and computer use may also help you child learn. Your school and health care provider can help you arrange these services and appropriate therapy when needed.

3. Medical care and medications

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

   Your provider may prescribe medications that can improve a 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 provider 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

A special type of blood text called an FMRI-DNA test.

The DNA test is able to analyze the structure of the fragile X gene in great detail. DNA is like a twisted ladder and the rungs of the ladder carry the mutation or the change in the DNA. There is an excessive number of chemical repeats, called CGG repeats, down the rungs of the DNA ladder where the fragile X gene is located. All people have the fragile X gene and it normally produces the fragile X protein, which is very important for normal brain development. Most people have between 5 to 44 CGG repeats in their fragile X gene. Carriers, on the other hand, have between 55 to 200 repeats. Carriers usually have a normal IQ, but they occasionally may experience emotional difficulties, such as anxiety, learning problems, or even autism. Some male carriers who are over 50 years old develop tremors, balance problems, and sometimes dementia.

People with greater than 200 repeats have the full mutation and are significantly affected by fragile X syndrome. The DNA test can check how many repeats your child has.

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 or health care provider.

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 http://www.fragilex.org has a list of resource centers, parent support groups, and educational materials. 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 provider. He or she can help you. When you as parents are healthy, you can better help your child reach his or her optimal potential.