Fragile X Syndrome
A Genetic Disorder
The Science of Fragile X
Fragile X syndrome is a genetic disorder that is caused by a defect in the FMR1 gene located on the X chromosome. It is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, which is one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. X-linked dominant means that in females (who have two X chromosomes), a mutation in one of the two copies of a gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of a gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A male child usually inherits only one X chromosome, from his mother. If that X chromosome had the fragile X mutation, the child most likely will have the full fragile X syndrome because the Y chromosome (inherited from his father) does not carry the genetic information that can compensate for the problem. A female, however, normally inherits two X chromosomes, one from each parent. If one of the X chromosomes has the fragile X mutation, the other X chromosome, inherited from her unaffected parent, can partially compensate for the incorrect genetic information. About half of affected females show no symptoms of fragile X syndrome. The other half of affected females displays symptoms, especially learning disabilities, behavioral problems or intellectual impairment. Fragile X occurs in about 1 in 4,000 males and 1 in 8,000 females.
The Signs and Symptoms
People with Fragile X do not all have the same signs and symptoms, but they do have some things in common. Fragile X syndrome is a condition that causes a spectrum of developmental and behavioral problems which tend to be more severe in males than in females. It is the most common form of inherited intellectual disability. Fragile X syndrome typically causes moderate intellectual disability in males, although the severity of intellectual impairment varies from person to person. A small number of males do not have intellectual disability, defined as an IQ below 70. About a third of women with fragile X syndrome have no cognitive impairment, while the remainder have some degree of cognitive, behavioral, or social difficulties. Some females with fragile X syndrome have mild intellectual disability. As infants, children with fragile X syndrome may display poor muscle tone, gastric reflux, and frequent ear infections. Their motor and mental milestones, as well as their speech, tend to be delayed. They, boys especially, may have trouble speaking clearly, may stutter, or may leave out parts of words. They may also have problems understanding other people’s social cues, such as tone of voice or specific types of body language. Children with fragile X syndrome often have behavioral problems such as anxiety, hyperactivity, hand-flapping, biting, and temper tantrums. About one-third of males with fragile X have autism or autism-like behavior. In females, who often have milder symptoms, behavioral problems may appear as depression, shyness, and avoidance of social situations. Some people with the condition have Attention Deficit Disorder (ADD), with an inability to sustain focused attention on a specific task. As they become adolescents and young adults, people with fragile X syndrome – particularly males – may lack impulse control, make poor eye contact, and/or be easily distracted. Many children with Fragile X are bothered by certain sensations, such as bright light, loud noises, or the way certain clothing feels on their bodies. They often have unusual responses to being touched or to sights and sounds. Males with fragile X syndrome often share characteristic physical features such as long, narrow face with a prominent jaw and forehead, a large head, flexible joints, and large ears. These symptoms tend to be milder or absent in females with the condition. After puberty, males with fragile X syndrome typically have enlarged testicles. Roughly 15 percent of males and 5 percent of females with fragile X will experience seizures. While some experience heart murmurs from a condition called mitral valve prolapse, it is usually harmless and may not require treatment.
Treating Fragile X
The “FMR1 DNA Test” (sometimes called the “Fragile X DNA Test”) became the “standard of care” for determining the presence of Fragile X. DNA testing detects more than 99 percent of individuals (both males and females) with FXS, as well as Fragile X carriers. There is no way to correct or remove the extra CGG repetitions that cause fragile X syndrome. Treatment focuses on relieving symptoms and maximizing potential. Treatment plans include psychological counseling for the affected child and family, occupational and speech therapy, as well as medication to treat hyperactivity, attention difficulties, violent outbursts, and other behavioral problems. A special education program with modifications in classroom environment, teaching materials and curriculum may also be available. For adolescents and adults with mental impairment, vocational training, and, if necessary, placement in a group home is accessible. While those diagnosed with fragile X syndrome may have learning and behavioral problems, they generally do not have major medical problems and can live a normal life span.