Fragile X-associated tremor/ataxia syndrome
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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder most frequently seen in male premutation carriers of Fragile X syndrome (FXS) over the age of 50.[4][5] The main clinical features of FXTAS include problems of movement with cerebellar gait ataxia and action tremor.[4][6] Associated features include parkinsonism, cognitive decline, and dysfunction of the autonomic nervous system.[4][6] FXTAS is found in Fragile X "premutation" carriers, which is defined as a trinucleotide repeat expansion of 55-200 CGG repeats in the Fragile X mental retardation-1 (FMR1) gene.[7] 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome.[7]
Fragile X-associated tremor/ataxia syndrome | |
---|---|
Abbreviation: | FXTAS |
Pronunciation: | "FAX-tass"[1] |
Location of the FMR1 gene | |
Specialty: | Neurology, Movement Disorders |
Symptoms: | intention tremor, ataxia, and parkinsonism |
Prevalence: | In patients over 50 with FMR1 premutation: |
Onset: | Late-onset, diagnosed in patients >50 years[1] |
Diagnosis: | Presentation, family history, genetic testing, and MRI |
In contrast to FXS full mutation, which is diagnosed early in childhood, symptoms of FXTAS manifest in individuals over the age of 50.[1] Like FXS, FXTAS is most common and most severe in males due to the mutation's X-linked inheritance pattern.[2] FXTAS has an incidence of 30-40% (male) and 8-15% (female) among FXS premutation carriers over the age of 50.[2][3]
FMR1 mRNA is found to be elevated in patients with FXTAS[7] in contrast to FXS, where the FMR1 gene is transcriptionally silenced via DNA methylation.[8] 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.[7]
There is no cure for FXTAS, but several of the symptoms can be managed with medication.[7]