Fragile X-associated tremor
| Fragile X-associated tremor/ataxia syndrome | |
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| Abbreviation: | FXTAS |
| Pronunciation: | "FAX-tass" |
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| Specialty: | Neurology, Movement Disorders |
| Symptoms: | intention tremor, ataxia, and parkinsonism |
| Prevalence: | In patients over 50 with FMR1 premutation:
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| Onset: | Late-onset, diagnosed in patients <50 years |
| Diagnosis: | Presentation, family history, genetic testing, and MRI |
| OMIM code: | 300623 |
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with male premutation carriers of Fragile X syndrome (FXS) over the age of 50. The main clinical features of FXTAS include problems of movement with cerebellar gait ataxia and action tremor. Associated features include parkinsonism, cognitive decline, and dysfunction of the autonomic nervous system. FXTAS is found in Fragile X "premutation" carriers, which is defined as a trinucleotide repeat expansion of 55-200 CCG repeats in the Fragile X mental retardation-1 (FMR1) gene. 4-40 CCG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome.
In contrast to FXS full mutation, which is diagnosed early in childhood, symptoms of FXTAS manifest in individuals over the age of 50. Like FXS, FXTAS is most common and most severe in males due to the mutation's X-linked inheritance pattern. FXTAS has an incidence of 40-45% (male) and 16.1% (female) among FXS premutation carriers over the age of 50.
FMR1 mRNA is found to be elevated in patients with FXTAS in contrast to FXS, where the FMR1 gene is transcriptionally silenced via DNA methylation. In both diseases the FMR1 gene product, Fragile X mental retardation protein (FMRP) is diminished, but in FXTAS this is believed to be mediated by RNA toxicity, while in FXS, FMRP is absent due to transcriptional silencing.
There is no cure for FXTAS, but several of the symptoms can be managed with medication.
The physical symptoms of FXTAS include an intention tremor, cerebellar 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: hypertension, bowel and bladder dysfunction, and impotence.
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