Fragile X Syndrome

Fragile X syndrome is a genetic condition caused by mutations in the FMR1 gene. The defective gene results in a range of developmental problems including learning disabilities and mental retardation. It occurs in approximately 1 in 4,000 males and 1 in 8,000 females.

Symptoms

Not everyone with Fragile X has the same signs and symptoms, but they do have some things in common. Symptoms are often milder in girls than in boys.  Here are some common signs of Fragile X:

• Intelligence and learning - Many people with Fragile X have intellectual disabilities.  These problems can range from mild learning disabilities to more severe mental retardation. 
• Physical - Teens and adults with Fragile X may have long ears, faces, and jaws.  Many people with Fragile X may also have loose, flexible joints. They may have flat feet and be able to extend joints like the thumb, knee, and elbow further than normal.
• Social and Emotional - Most children with Fragile X have some behavior challenges.  They may be afraid or anxious in new situations.  Many children, especially boys, have trouble paying attention or may be aggressive.  Girls may be shy around new people.
• Speech and Language - Most boys with Fragile X have some problems with speech and language.  They may have trouble speaking clearly, or may stutter, or leave out parts of their words.  They may also have problems understanding "clues" when talking to other people, such as understanding the speaker’s tone of voice or that person’s body language.  Girls usually do not have severe problems with speech or language.
• Sensory - Many children with Fragile X are bothered by certain sensations, such as bright light, loud noises, or the way something feels.  Some do not like to be touched, or have trouble making eye contact with other people

Causes

Mutations in the FMR1 gene cause fragile X syndrome.

Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times. The abnormally expanded CGG segment inactivates (silences) the FMR1 gene, which prevents the gene from producing a protein called fragile X mental retardation protein. Loss or a shortage (deficiency) of this protein leads to the signs and symptoms of fragile X syndrome.

Men and women with 55 to 200 repeats of the CGG segment are said to have an FMR1 premutation. Most people with a premutation are intellectually normal. In some cases, however, individuals with a premutation have lower than normal amounts of the fragile X mental retardation protein and features of fragile X syndrome.

In women, the premutation can expand to more than 200 repeats in cells that develop into eggs. This means that women with the FMR1 premutation have an increased risk of having a child with fragile X syndrome. By contrast, the premutation CGG repeat in men remains a premutation as it is passed to the next generation.

In a small percentage of cases, other types of mutations cause fragile X syndrome. These mutations delete part or all of the FMR1 gene or change one of the building blocks (amino acids) used to make the fragile X mental retardation protein. As a result, no protein is produced, or the protein is disabled because its size or shape is altered.

Fragile X syndrome is inherited in an X-linked dominant pattern.

Treatment

Currently there is no definitive, single treatment for Fragile X. However, there are a variety of ways to help minimize the symptoms of the condition. Children with Fragile X who receive appropriate education, behavioral or physical therapy, and medication have the best chance of using their individual capabilities and skills. Even those with significant mental retardation can learn to master many self-help skills.

One important factor in developing a child’s long-term potential is early intervention. The sooner a child begins to get help, the more opportunity for learning. Because a young child’s brain is still forming, early intervention gives children the best start possible and the best chance of developing their full potential. Even so, no matter when a person is diagnosed with Fragile X, it’s never too late to benefit from treatment.

Reference:

Genetics Home Reference, U. S. National Library of Medicine
National Institute of Child Health and Human Development, USA.