Fragile X-associated tremor/ataxia syndrome

Overview

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder associated with problems with movement, memory, and the autonomic nervous system. Though it also involves the fragile X gene, fragile X syndrome is a much different clinical syndrome.

FXTAS can present with many of the same symptoms of multiple system atrophy, and often includes parkinsonism, dysautonomia, peripheral neuropathy, and dementia. It is caused by a trinucleotide repeat disorder in the fragile X mental retardation 1 gene, FMR1. It most often occurs in men, but can present in women. There is no cure for FXTAS, but several of the symptoms can be made better with medication.

Symptoms

The physical symptoms of FXTAS include an intention tremor, ataxia, and parkinsonism (this includes small, shuffling steps, muscle rigidity and slowed speech), as well as neuropathic symptoms. As the disease progresses to the more advanced stages, an individual with FXTAS is also at risk of autonomic dysfunction. This includes hypertension, bowel and bladder dysfunction, and impotence.

An individual with FXTAS may also exhibit the following symptoms: a decrease in cognition, which includes diminishing short-term memory and executive function skills, declining math and spelling abilities and decision-making abilities. FXTAS may also result in changes in personality, due to alterations of the limbic area in the brain. This includes increased irritability, angry outbursts, and impulsive behaviour

 

Source:Wikipedia

Causes

FXTAS is a late onset (over age 50) neurological condition. It occurs in individuals who have a specific change in the “Fragile X” gene, which is on the X chromosome. This gene is called the FMR1 gene. The specific change is called a Fragile X or FMR1 premutation. Individuals who have an FMR1 premutation are Fragile X “carriers,” meaning they may not experience any of the symptoms of Fragile X syndrome but “carry” the potential to pass the premutation on to their offspring (more on this below). Not all carriers will develop FXTAS, but all individuals with FXTAS have an FMR1 premutation. Researchers are investigating what other factors might contribute to FXTAS in FMR1 premutation carriers.

The FMR1 gene can undergo changes that cause FXTAS and other Fragile X-associated Disorders (conditions caused by genetic changes on the "X" chromosome, which often affect males more than females). These changes affect a pattern of DNA called CGG repeats. Typically, the FMR1 gene has up to 54 of these CGG repeats. A premutation in the FMR1 gene results in 55-200 CGG repeats, and a full mutation results in more than 200 CGG repeats. Individuals with a full mutation are not at risk for FXTAS, but often have fragile X syndrome.

 

Source: FXTAS

Prevention

Since it is a genetic disorder, there is no possible way to prevent it

Diagnosis

When evaluating whether an individual has FXTAS, he or she must first be a confirmed premutation carrier. The symptoms of FXTAS are divided into “minor” and “major” clinical and MRI findings. The diagnosis is then categorized into “definite,” “probable” or “possible” FXTAS. The criteria were developed primarily as a reflection of the presenting symptoms in men. As we learn more about FXTAS in females, the diagnostic criteria may become different for females, since they usually have milder symptoms.

Also, there are symptoms of FXTAS that are considered “co-morbid,” which means they often occur in individuals with FXTAS but aren’t used to confirm the diagnosis (just as a sore throat is a symptom of strep throat, but cultures, fever, etc. are also used to make the diagnosis).

 

Source: FXTAS

Treatment

here are three purposes of therapy for FXTAS: to reduce symptoms, to slow the progression of disease, and to cure disease. While there are no known treatments to slow progression or cure FXTAS, intense research is being done in this regard. There are a number of treatments that many affected persons have found helpful in reducing symptoms and disability.

 

In general, therapy that is most likely to help in any disease has been tested in well designed and executed clinical trials. However, FXTAS was only first published in 2001, so there has not yet been any treatments studied well enough to know if they definitely help. Until we have proven therapies for FXTAS, it is reasonable to consider treatments that have been shown to reduce the same symptoms when they occur in other diseases. For example, many persons with FXTAS and shaking in their hands (tremor) will find that taking a medication that reduces hand shaking in another disease, e.g., essential tremor, is helpful.

 

Each person with FXTAS is unique; each will have their own set of problems. While most will have hand shaking and balance problems, these will vary in severity and the need for treatment. Further, each affected person has a unique medical history, biological make-up and personality. The symptoms of FXTAS are known to vary from one person to another; so the best treatment options vary from person to person.

Useful treatments for FXTAS include medications, psychological and genetic counseling, rehabilitative treatments such as speech, occupational and physical therapy, gait training and surgery. Family supportive services and counseling are important also. While many of the FXTAS symptoms are neurological, many other body systems are also affected. To receive optimal care it is best to have a medical care team that is knowledgeable about FXTAS. The team should include a neurologist and primary care physician at a minimum. Other specialists, e.g. in the areas of psychiatry, psychology, rehabilitation, urology, cardiology, and movement disorders neurology, may also be needed. The following article describes the current knowledge of treatment of FXTAS.

 

Source: FXTAS