FXTAS, or fragile X-associated tremor/ataxia syndrome, is one of three known Fragile X-associated Disorders (FXDs). All the FXDs are caused by changes in the FMR1 Gene.
What Is FXTAS?
FXTAS is an “adult onset” neurodegenerative disorder, occurring more commonly in males than females. Onset is usually over 50 years of age, and most individuals had no related medical, developmental or neurological problems prior to the appearance of FXTAS symptoms. Females comprise only a small part of the FXTAS population, and their symptoms tend to be less severe.
What Are the Symptoms of FXTAS?
The features of FXTAS include:
- Ataxia (balance problems).
- Intention tremors (during intentional movement such as pouring, writing, etc,).
- Memory loss (usually short-term).
- Mood instability, irritability, personality change, psychiatric symptoms.
- Parkinson’s symptoms (many individuals will be misdiagnosed with Parkinson’s Disease” prior to diagnosis of FXTAS).
- Dementia (many individuals will be misdiagnosed with Alzheimer’s disease prior to diagnosis FXTAS).
- Cognitive decline (loss of math, reading, and verbal comprehension skills).
- FXTAS progresses at varying rates in different individuals.
What Causes FXTAS?
FXTAS is caused by a change or mutation in a gene called the FMR1 gene. All individuals with FXTAS have what is called an FMR1 premutation and are considered Carriers. Men with FXTAS inherited this genetic change from their mother, women with FXTAS can inherit it from their mother or father. See Genetics and Inheritance for more information.
Can You Pass FXTAS on to Your Children?
Anyone with an FMR1 premutation can pass the gene mutation on to their children. Not everyone with the FMR1 mutation will get FXTAS. Males with the FMR1 premutation will pass it on to all their daughters and none of their sons. Females with the premutation will have a 50/50 chance in each pregnancy to pass it on to children of both genders. Women with the premutation can potentially have children with fragile X syndrome.
How Is FXTAS Diagnosed?
FXTAS is usually diagnosed by a neurologist, a specialist in movement disorders, a geneticist, or psychiatrist. Individuals who exhibit any FXTAS symptoms, whether they are known to be FMR1 carriers or not, should be evaluated by one of these specialists.
- 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.
- The Lancet Neurology Vol 12 No. 8 Aug 2013
Paul Hagerman discusses a Review which highlights the latest clinical and molecular understanding of the FMR1 mutation and FXTAS.
Podcast: Download (Duration: 10:28 — 9.6MB)
- Call or email the National Fragile X Foundation (800) 688-8765 or email@example.com and ask for a FXTAS packet.
- Visit our website focused on FXTAS at www.fxtas.org.