The fragile x-associated tremor and ataxia syndrome (FXTAS)

Abstract

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late-onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease. Key words: FXTAS, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, movement disorders, essential tremor, gait ataxia, CGG repeats, FMR1 gene.A síndrome de tremor e ataxia associada ao X frágil (FXtAs) resumo A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome. Palavras-chave: FXTAS, tremor e ataxia associados ao X frágil, síndrome do X frágil, distúrbios do movimento, tremor essencial, ataxia de marcha, repetições CGG, gene FMR1.

FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile

“…Under-diagnosis of FXTAS is possibly due to the limited knowledge about this syndrome and also because of the clinical variability. Recognizing FXTAS in patients from various ethnic backgrounds and international locations would contribute to our understanding of the phenotypic variation of this disease [26]. …”

Low diagnostic accuracy of fragile X tremor/ataxia syndrome diagnostic criteria in late onset ataxia

“…The Fragile X mental retardation 1 ( FMR1 ) gene (Xq27.3) has a 5'UTR region that presents a zone of Cytosine‐Guanine‐Guanine (CGG) microsatellites; normal alleles present up to 40 repeats, and 41 to 54 repeats are considered a gray zone (GZ). Premutation is defined between 55 to 199 repeats (PM), and full mutation (FM) is when 200 or more repeats are found (cause of Fragile X Syndrome; FXS Online Mendelian Inheritance in Man, OMIM® #300624).…”

Parkinson's disease: chameleons and mimics

“…FXTAS is caused by a pre-mutation expansion (55–200 repeats) of the CGG trinucleotide repeat in the fragile X mental retardation-1 (FMR1) gene. Although FXTAS can be mistaken for PD, it is more likely to be mistaken for multiple system atrophy-cerebellar subtype or cerebellar ataxia 52 53…”