FXTAS is a condition that develops in some men and women who have an altered form of a specific gene. People with FXTAS have a change or mutation in a gene called the Fragile X Mental Retardation 1 (FMR1) gene. This gene is found on the X chromosome.

FXTAS occurs later in life (in people older than age 50) and is characterized by tremors when making purposeful movements, balance problems, Parkinson's-like symptoms such as muscle stiffness or rigidity, and memory loss. Most people have no symptoms until the onset of the condition later in life.

FXTAS is less common among women, and their symptoms are often milder, but having the FMR1 premutation still puts them at risk for FXTAS.

Although FXTAS affects individuals differently, the symptoms of the disorder are similar to those of Parkinson's or Alzheimer's disease, including memory loss, slowed speech, tremors, and a shuffling gait. Some people will have many symptoms that appear quickly and get worse over time. Others have only a few mild symptoms.

Men have slightly different symptoms of FXTAS than women do. Symptoms of FXTAS in men include:

• Balance problems, called ataxia (pronounced uh-TAK-see-uh)
• Intention tremor (shaking when trying to perform purposeful movements, such as touching one's nose or grabbing something)
• Parkinson's-like symptoms, such as muscle stiffness or rigidity, a shuffling gait or walk, and slowed speech
• Memory loss, including forgetting how to do things that were once done easily (such as balancing a checkbook), getting lost going to familiar places, or forgetting the names of everyday objects
• Irritability and moodiness
• Low blood pressure
• Numbness or burning in the hands and feet
• Incontinence
• Impotence
• Loss of reading skills and math skills
• Difficulty learning new things

Women with FXTAS may have the following symptoms:

• High blood pressure
• Balance problems, called ataxia
• Premature ovarian failure
• Intention tremors
• Seizure disorders
• Thyroid problems (usually an underactive thyroid gland, called hypothyroidism)
• Muscle pain such as fibromyalgia

Symptoms of FXTAS usually develop after age 50. The average age of people newly diagnosed with FXTAS is about 61.

Some medical conditions are reported to be associated with the FMR1 premutation, but only in men. These include:

• Abnormal heart rhythm (arrhythmia)
• Balance disorders
• Congestive heart failure
• High blood sugar
• Sleep apnea
• Mood disorders, including major depressive disorder, anxiety disorder, and post-traumatic stress disorder

High blood pressure is also associated with FXTAS in both men and women, but it seems to be more common among women with the FMR1 premutation.

Because FXTAS occurs only in those who have the premutation on the FMR1 gene, the premutation is related to the condition.

If the premutation was the only cause of FXTAS, then everyone with the premutation would develop FXTAS after age 50. However, it is still not clear why some people with the premutation develop FXTAS while others do not. This topic is an active area of study.

People with FXTAS have a change or mutation in the FMR1 gene found on the X chromosome.

In the gene, the information for making a protein has two parts: the introduction, and the instructions for making the protein itself. Researchers call the introduction the promoter because of how it helps to start the process of building the protein.

The promoter part of the FMR1 gene includes many repeats—repeated instances of a specific DNA sequence called the CGG sequence. A normal FMR1 gene has between 6 and 40 repeats in the promoter; the average is 30 repeats.

People with between 55 and 200 repeats have a premutation of the gene. The premutation causes the gene to not work properly, but it does not cause intellectual and developmental disability (IDD). FXTAS occurs in some people who have the premutation.

The premutation is also related to fragile X-associated primary ovarian insufficiency (FXPOI).

People with 200 or more repeats in the promoter part of the gene have a full mutation, meaning the gene might not work at all. People with a full mutation often have fragile X syndrome, the most common inherited form of IDD. Individuals with the full mutation are not at risk for FXTAS.

Inheriting FXTAS

Anyone with the FMR1 gene mutation can pass it to their children. However, a person who inherits the gene may not develop FXTAS. Males will pass it down to all of their daughters and not their sons. Females have a 50/50 chance to pass it along to both their sons and daughters. In addition, parents can have children with a condition associated with Fragile X even if the parents do not have that condition themselves.

Premutation genes—the kind associated with FXTAS and characterized by 55 to 199 extra CGG sequences in the FMR1 gene—can grow spontaneously from generation to generation. That is, the gene's CGG sequences can increase in number on their own. They can even expand to the level of full mutation (200 or more CGG sequences), making fragile X syndrome more likely.

The FMR1 premutation form is more likely to expand depending on the number of CGG repeats it has. The greater the number, the greater the risk of expansion. Risk also increases with each passing generation.

Health care providers can order a blood test to determine if a person who has symptoms of FXTAS is a carrier. A laboratory will conduct the tests to determine what form of the FMR1 gene is present.

However, FXTAS is often misdiagnosed. The condition was identified only recently―in 2001—so it is not as familiar to health care providers as other common disorders in seniors, such as Alzheimer's disease and Parkinson's disease. The similarity of symptoms can lead some health care providers to pursue those conditions before considering FXTAS. Many of the FXTAS symptoms, such as memory problems and balance problems, may also be seen as natural parts of aging.

A health care provider may use a combination of a blood test, symptoms, and information from brain imaging, such as magnetic resonance imaging (MRI), to confirm a FXTAS diagnosis. In about one-half of men and one-fifth of women with FXTAS, MRIs show white matter lesions (areas of dead cells) in the middle cerebellar peduncle of the brain.

Before NICHD-supported researchers discovered FXTAS in 2001, it was often misdiagnosed. The symptoms of FXTAS—memory loss, tremors, muscle stiffness or rigidity, a shuffling gait or walk, and slowed speech—are similar to Alzheimer's disease and Parkinson's disease symptoms.

A characteristic of FXTAS is also ataxia, which means clumsiness of movement or loss of coordination that is not due to muscle weakness. Ataxia is most often caused by loss of function in the cerebellum, the part of the brain that controls the body's coordination. It can also be caused by problems with the motor sensory pathways leading in and out of the cerebellum. Although symptoms of FXTAS are similar to those of other conditions, its diagnosis is unique due to the white matter lesions (areas of dead cells) in the cerebellum.

Certain medications and therapies are helpful for treating symptoms of FXTAS and may help slow its progression. However, no treatment can stop FXTAS from progressing and none is considered a cure.

Symptoms of FXTAS differ from person to person, and treatment should address a person's individual needs. Health care providers may work as a team to provide appropriate treatment, such as physical therapy for difficulty with movement and balance, medication for tremors, and psychological counseling and support services for the individual and family. Other therapies may include rehabilitative treatments such as speech and occupational therapy and gait training. A urologist may be consulted regarding sexual health.

In addition, the children of FXTAS patients may want to confirm their FMR1 gene status and to discuss their situation with a genetic counselor.

In many cases, medications have been used to treat symptoms associated with FXTAS, as shown in the table below.

Please note that the NICHD does not endorse or support the use of any of these medications in treating symptoms of FXTAS, or for other conditions for which the medications are not approved by the U.S. Food and Drug Administration.

Other medications for urinary urgency, bowel incontinence, difficulty swallowing, dizzy spells, high blood pressure, pain, and thyroid dysfunction may also be used.