ATYPICAL CLINICAL COURSE OF FXTAS: RAPIDLY PROGRESSIVE DEMENTIA AS THE MAJOR SYMPTOM

The fragile X–associated tremor/ataxia syndrome (FXTAS) is a progressive neurologic disorder that may affect carriers of premutations of the FMR1 gene (55 to 200 CGG repeats), mainly men older than 50 years of age. These individuals do not have the mental retardation syndrome, which is caused by the FMR1 gene full mutation (>200 CGG repeats). The major FXTAS features include progressive intention tremor and cerebellar ataxia, often accompanied by progressive cognitive and behavioral disturbances, such as memory loss, anxiety, deficits of executive functions, and reclusive or irritable behavior, with a gradual appearance of dementia in some individuals; parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction may be present.¹ Severe dementia has been seen in a limited number of patients.² Neuropsychological assessments in 29 FXTAS patients revealed that 21% had Full Scale IQs <85, reflecting severe cognitive impairment or dementia.³ Neuropsychiatric manifestations (agitation/aggression, depression, apathy, disinhibition, and irritability) compatible with frontal-subcortical dementia were documented as significantly greater in patients with FXTAS vs normal age-matched controls.^{4 …}