The fragile X-associated tremor/ataxia syndrome is characterized by intention tremor and ataxia in people who are premutation carriers of the Fragile X gene. Patients with this disorder might also demonstrate signs of dementia with parkinsonian features. We report a patient with dementia and parkinsonian signs who did not demonstrate an intention tremor or gait ataxia.
A 58-year-old woman who had 2 sons with fragile X retardation syndrome and was a carrier, developed progressive dementia, including impaired memory, executive dysfunction, nonfluent speech, and parkinsonian signs, but had no action-intention tremor and no gait ataxia. Magnetic resonance imaging revealed extensive abnormalities of the white matter.
On post-mortem examination, 7 years after this evaluation, she demonstrated extensive subcortical white matter pallor (spongiosis) and widespread ubiquitin-positive intranuclear inclusions in both neurons and in protoplasmic astrocytes characteristic of fragile X-associated tremor/ataxia syndrome, but no spongiosis in the cerebellar peduncles a defining feature of this tremor/ataxia syndrome.
Patients who present with dementia and signs of Parkinson syndrome, even in the absence of ataxia or intention tremor should be evaluated for this fragile X dementia parkinsonism syndrome.
Departments of *Neurology, Center for Neuropsychological Studies and Dementia
†Departments of Neurology and Neuropathology, University of Florida College of Medicine
‡Department of Neurology, University of North Carolina
§Departments of Neurology and Neuropathology, The Veterans Affairs Medical Center, Gainesville, FL
Reprints: Kenneth M. Heilman, MD, Department of Neurology, Box 100236, University of Florida College of Medicine, Gainesville, FL 32610 (e-mail: Heilman@neurology.ufl.edu).
Received for publication February 24, 2009
accepted June 21, 2009
The authors report no conflicts of interest.
This study was supported in part by the State of Florida, Department of Elder Affairs, the University of Florida Memory Disorder Clinics and the Department of Veterans Affairs.
Presented at the American Academy of Neurology, April 2008, Chicago, IL.