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Fragile X–associated tremor/ataxia syndrome
Author(s) -
Hagerman Paul J.,
Hagerman Randi J.
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12693
Subject(s) - fmr1 , parkinsonism , ataxia , fragile x syndrome , intention tremor , neuroscience , gait ataxia , atrophy , trinucleotide repeat expansion , cerebellar ataxia , medicine , cognitive decline , psychology , disease , biology , genetics , fragile x , allele , psychiatry , dementia , pathology , gene
Fragile X–associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder that affects some but not all carriers of small, noncoding CGG‐repeat expansions (55–200 repeats; premutation) within the fragile X gene ( FMR1 ). Principal features of FXTAS include intention tremor, cerebellar ataxia, Parkinsonism, memory and executive function deficits, autonomic dysfunction, brain atrophy with white matter disease, and cognitive decline. Although FXTAS was originally considered to be confined to the premutation range, rare individuals with a gray zone (45–54 repeats) or an unmethylated full mutation (>200 repeats) allele have now been described, the constant feature of the disorder remaining the requirement for FMR1 expression, in contradistinction to the gene silencing mechanism of fragile X syndrome. Although transcriptional activity is required for FXTAS pathogenesis, the specific trigger(s) for FXTAS pathogenesis remains elusive, highlighting the need for more research in this area. This need is underscored by recent neuroimaging findings of changes in the central nervous system that consistently appear well before the onset of clinical symptoms, thus creating an opportunity to delay or prevent the appearance of FXTAS.