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Maureen A. Leehey, MD; Renato P. Munhoz, MD; Anthony E. Lang, MD; James A. Brunberg, MD; Jim Grigsby, PhD; Claudia Greco, MD; Sebastian Jacquemont, MD; Flora Tassone, PhD; A. M. Lozano, MD, PhD; Paul J. Hagerman, MD, PhD; Randi J. Hagerman, MD

Arch Neurol. 2003;60:117-121.

Context  The fragile X premutation has recently been reported to be associated with a neurodegenerative syndrome, chiefly characterized by intention tremor, gait ataxia, and executive cognitive deficits in men older than 50 years. Essential tremor is a frequent cause of tremor in elderly patients and in some cases is associated with impaired tandem gait and cognitive deficits.

Objective  To describe 2 fragile X carriers whose clinical presentation mimicked essential tremor.

Design  The 2 patients described herein underwent neurologic examinations by experienced movement disorders neurologists, magnetic resonance imaging, and fragile X gene, messenger RNA, and protein analyses. One underwent detailed neuropsychological testing.

Setting  Patients were studied at 2 large university movement disorders clinics.

Patients  Both patients were white men older than 50 years who had been diagnosed as having essential tremor and then found to be fragile X carriers.

Results  Besides disabling intention tremor, the 2 patients had impaired tandem, generalized brain atrophy, and unusual bilateral T2 middle cerebellar hyperintensities on magnetic resonance imaging. The patient who underwent neuropsychological testing had frontal executive deficits. Both patients had elevated fragile X mental retardation gene 1 messenger RNA and reduced fragile X mental retardation 1 protein levels.

Conclusion  The fragile X carrier state may underlie the clinical findings in some older men diagnosed as having essential tremor.

From the Departments of Neurology (Dr Leehey) and Medicine (Geriatrics) (Dr Grigsby), University of Colorado Health Sciences Center, Denver; Division of Neurology, Department of Medicine (Drs Munhoz and Lang), and the Division of Neurosurgery (Dr Lozano), University of Toronto and Toronto Western Hospital, Toronto, Ontario; Departments of Radiology (Dr Brunberg), Pathology (Dr Greco), and Biological Chemistry (Drs Tassone and P. Hagerman), University of California at Davis School of Medicine, Davis; and M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento (Drs Jacquemont and R. Hagerman).

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