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Fragile X associated tremor-ataxia syndrome (FXTAS)

Neurodegenerative diseases

General description

Fragile X-associated tremor-ataxia syndrome (FXTAS) represents a neurodegenerative disorder manifesting in adulthood among carriers of the causative gene for Fragile X syndrome (FXS). The etiology of this disease is linked to an abnormal expansion of CGG trinucleotide repeats in the FMR1 gene, following an X-linked inheritance pattern.

FXTAS is characterized by a spectrum of neurological manifestations, including cerebellar ataxia, intention tremor, parkinsonian features, cognitive decline, and peripheral neuropathy. A review of family history often uncovers instances of mental retardation and abnormal behavior in descendants, such as children or grandchildren. Additionally, female patients may exhibit infertility and early menopause alongside the aforementioned symptoms.

Initially, FXTAS was considered a distinct clinical entity separate from Neuronal intranuclear inclusion disease (NIID). However, current understanding recognizes NIID and FXTAS as part of a disease spectrum.

T2WI and FLAIR hyperintensity (MCP sign)

Non-SOL
  • Middle cerebellar peduncle
  • Cerebrum
    Cerebral white matter
  • Cerebellum
    Cerebellar white matter
Symmetric
Bilateral
T2WI
Hyperintensity
FLAIR
Hyperintensity

MRI shows T2WI and FLAIR hyperintensities in the middle cerebellar peduncle in approximately 60% and 13% of affected male and female patients. Atrophy involving cerebrum and cerebellum with nonspecific white matter T2WI and FLAIR hyperintensity may also be observed.

Paravermal sign

Non-SOL
  • Cerebellum
    Paravermis
Symmetric
Bilateral
T2WI
Hyperintensity
FLAIR
Hyperintensity

Paravermal FLAIR hyperintensity (paravermal sign), which was originally thought as specific finding of Neuronal intranuclear inclusion disease (NIID) and FXTAS, can also be found in Dentatorubral-Pallidoluysian Atrophy (DRPLA).

Corticomedullary junction DWI hyperintensity

Non-SOL
  • Cerebrum
    Cerebral white matter
    Subcortical white matter
    U-fiber
Symmetric
Bilateral
Linear
DWI
Hyperintensity

DWI hyperintensity along corticomedullary junctions, which was originally considered as specific finding of Neuronal intranuclear inclusion disease (NIID), can also be found in FXTAS, Oculopharyngeal myopathy with leukoencephalopathy (OPML), and Oculopharyngodistal myopathy (OPDM).