Fragile X

Fragile-X associated tremor/ataxia (FXTAS)

FXTAS is a very common tremor/ataxia syndrome, which is newly described (as of 2001). It is a late-onset disorder, typically beginning in the 60's or 70's, with involvement of multiple systems -- gait ataxia, intention tremor, peripheral neuropathy, autonomic dysturbance, and sometimes dementia. MRI shows atrophy, white matter changes, and distinctive T2 hyperintensities in the middle cerebellar peduncles. FXTAS may affect as many as 1/3000 men over the age of 50. (Hall et al, 2005). About 3% of persons being tested for hereditary cerebellar disorders are positive for FXTAS. There is no treatment, but genetic counseling may be helpful.

Males transmit this gene to all daughters. Thus the inheritance pattern of the disease itself goes from father->daughter->male children. Female carriers (the daughters) have a 50% chance of transmitting the gene to each child (male or female).

Proposed criteria for genetic testing (FMR1) are:

• Unexplained cerebellar ataxia in men older than 50
• Action tremor, parkinsonism or dementia in men older than 50 with one of the following
  • a) A family history of developmental delay, autism, mental retardation, or premature ovarian failure
  • b). The middle cerebellar peduncle sign on MRI.

High signal seen in both middle cerebellar peduncles in person with Fragile X associated tremor ataxia.

References:

• Hall DA and others. Initial diagnoses given to persons with the fragile X associated tremor/ataxia (FXTAS).