Fragile X–associated tremor/ataxia syndrome (FXTAS) is an “adult onset” neurodegenerative disorder, usually affecting males over 50 years of age. Females comprise only a small part of the FXTAS population, and their symptoms tend to be less severe.
FXTAS affects the neurologic system and progresses at varying rates in different individuals.
All individuals with FXTAS are carriers of what is called a “premutation” of the FMR1 (Fragile X) gene (also known as “premutation carriers”).
In its “full mutation” form the FMR1 gene causes Fragile X syndrome (FXS), a different, but genetically related disorder that is present from birth but is often undiagnosed or misdiagnosed for many years.
Female “premutation carriers” can also be affected by Fragile X-associated primary ovarian insufficiency (FXPOI), another of the conditions associated with the change in the FMR1 gene.
What Is FXTAS?
As mentioned, all individuals with FXTAS are premutation carriers of the FMR1 gene (CGG repeats 55-200). The “job” of the FMR1 gene is to make protein (FMRP) that is important in brain development.
Researchers believe that (for unknown reasons) having the premutation leads to the overproduction of FMR1 mRNA (which contains the expanded repeats). They believe that the high levels of mRNA are what cause the signs and symptoms of FXTAS, but more research is needed.
Note: Not all premutation 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.
Symptoms in Males
Both the type and severity of FXTAS symptoms vary among individuals. Some will have multiple symptoms that progress rapidly, others few symptoms that remain mild over many years. The most common symptoms in males are:
- “Intention” or “action” tremor (trembling hands that occur when one reaches for something or is otherwise using one’s hands. The tremor is not as noticeable at rest).
- Balance problems, called “ataxia,” which might result in occasional or frequent falls or the need for the person to hold on to a railing or use a cane.
- “Parkinsonism,” which can include general shaking of body parts, muscle rigidity, a shuffling gait and slowed speech.
- Cognitive/intellectual decline, including short-term memory loss, loss of math or spelling skills, difficulty making decisions, and other intellectual functions.
- Numbness or burning of the hands and feet (neuropathy).
- Low blood pressure (orthostatic hypotension).
- Personality or mood changes, which might include increased irritability, outbursts of anger, and inappropriate or impulsive behavior not typical of or consistent with the person’s previous personality.
- Difficulty with organizing, planning, anticipating, and carrying out of everyday life tasks and activities (“executive function skills”).
- Difficulty learning new tasks.
- In advanced cases, loss of bowel or bladder control, impotence (autonomic dysfunction).
- Specific findings on a brain MRI called “increased signal intensity in the middle cerebellar peduncles (MCP) sign”. These findings are evident to neuroradiologists (radiologists with additional expertise in neurological conditions).
Symptoms in Females
Females can experience the same neurological symptoms as males, but almost always with less severity. Most affected women have some degree of tremor and/or ataxia. While the psychiatric and mood disorders are also less frequent in females, they are at higher risk for anxiety and depression in general. Additional symptoms affecting some females include:
- Fibromyalgia and/or generalized muscle pain.
- Thyroid disorders, usually hypothyroidism.
- Seizure disorders.
Find People and Professionals in the FXTAS Community
With FXTAS being a relatively new disorder, there may not appear to be as many services and professionals available as there is for other medical conditions. However, a number of support services and informational materials may be of value to those impacted by FXTAS, some of which address symptoms common to other medical conditions such as Parkinson’s.
The National Fragile X Foundation is on the lookout for more services and will continue to update this list below. In the meantime, we would welcome reader’s recommendations.
- Treatment of Fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems
- FXTAS – Clinical Features, Genetics & Testing Guidelines
An in-depth professional article covering all aspects of FXTAS. A great resource for doctors and professionals, but also provides great insight for family members.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55–200 repeats; premutation range) of a CGG trinucleotide in the Fragile X mental retardation 1 (FMR1) gene, the same gene which causes Fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made. © 2007 Movement Disorder Society
Key words: Fragile X-associated tremor/ataxia syndrome; tremor; ataxia; FMR1; Fragile X syndrome
- Fragile X-associated Tremor-Ataxia Syndrome Consensus Documents on Clinical Practices
Fragile X-associated Tremor-Ataxia Syndrome (2012-Oct)
Guidelines for best practices generated by consensus of all the physicians working on Fragile X. A great resource for doctors and professionals, but also provides great insight for family members.
Fragile X Clinics and Referrals
The National Fragile X Foundation offers free resources such as referrals to clinics and specialists.
Facebook Support Group
We have an online support group for people living with FXTAS and their caregivers. Click here to join.