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Progression of tremor and ataxia in male carriers of the FMR1 premutation

Authors

  • Maureen A. Leehey MD,

    Corresponding author
    1. Department of Neurology, University of Colorado at Denver and Health Sciences Center (UCDHSC), Denver, Colorado, USA
    • Department of Neurology, Box B183, University of Colorado at Denver Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262
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  • Elizabeth Berry-Kravis MD, PhD,

    1. Departments of Neurological Sciences, Pediatrics, and Biochemistry, RUSH University Medical Center, Chicago, Illinois, USA
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  • Sung-Joon Min PhD,

    1. Division of Health Care Policy and Research, Department of Medicine, UCDHSC, Denver, Colorado, USA
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  • Deborah A. Hall MD,

    1. Department of Neurology, University of Colorado at Denver and Health Sciences Center (UCDHSC), Denver, Colorado, USA
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  • Cathlin D. Rice MS,

    1. Department of Neurology, University of Colorado at Denver and Health Sciences Center (UCDHSC), Denver, Colorado, USA
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  • Lin Zhang MD, PhD,

    1. Department of Neurology, University of California at Davis School of Medicine, Sacramento, California, USA
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  • Jim Grigsby PhD,

    1. Division of Health Care Policy and Research, Department of Medicine, UCDHSC, Denver, Colorado, USA
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  • Claudia M. Greco MD,

    1. Department of Pathology, University of California at Davis Medical Center, Sacramento, California, USA
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  • Ann Reynolds MD,

    1. Department of Pediatrics, University of Colorado at Denver Health Sciences Center, Denver, Colorado, USA
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  • Rebecca Lara BS,

    1. Departments of Neurological Sciences, Pediatrics, and Biochemistry, RUSH University Medical Center, Chicago, Illinois, USA
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  • Jennifer Cogswell BA,

    1. M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento, California, USA
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  • Sebastien Jacquemont MD,

    1. Service de Génétique, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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  • David R. Hessl PhD,

    1. M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento, California, USA
    2. Department of Psychiatry, University of California Davis Medical Center, Sacramento, California, USA
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  • Flora Tassone PhD,

    1. M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento, California, USA
    2. Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Davis, California, USA
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  • Randi Hagerman MD,

    1. M.I.N.D. Institute, University of California at Davis Medical Center, Sacramento, California, USA
    2. Department of Pediatrics, University of California at Davis Medical Center, Sacramento, California, USA
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  • Paul J. Hagerman MD, PhD

    1. Department of Biochemistry and Molecular Medicine, University of California at Davis School of Medicine, Davis, California, USA
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Abstract

Premutation alleles of the fragile X mental retardation 1 (FMR1) gene give rise to a late-onset movement disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by progressive intention tremor and gait ataxia, with associated dementia and global brain atrophy. The natural history of FXTAS is largely unknown. To address this issue, a family-based, retrospective, longitudinal study was conducted with a cohort of 55 male premutation carriers. Analysis of the progression of the major motor signs of FXTAS, tremor and ataxia, shows that tremor usually occurs first, with median onset at ∼60 years of age. From the onset of the initial motor sign, median delay of onset of ataxia was 2 years; onset of falls, 6 years; dependence on a walking aid, 15 years; and death, 21 years. Preliminary data on life expectancy are variable, with a range from 5 to 25 years. © 2006 Movement Disorder Society

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