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The phenotypic spectrum of dystonia in Mohr–Tranebjaerg syndrome§

Authors

  • Ainhi D. Ha MBBS, FRACP,

    1. Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia
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  • Kaitlyn L. Parratt MBBS, FRACP,

    1. Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia
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  • Nanna D. Rendtorff PhD,

    1. Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine; The Panum Institute, University of Copenhagen, Copenhagen, Denmark
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  • Marianne Lodahl BBLT,

    1. Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine; The Panum Institute, University of Copenhagen, Copenhagen, Denmark
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  • Karl Ng MBBS, FRACP,

    1. Department of Neurology, Royal North Shore Hospital, Sydney, Australia
    2. Sydney Medical School, University of Sydney, Sydney, Australia
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  • Dominic B. Rowe MBBS, PhD, FRACP,

    1. Australian School of Advanced Medicine, Macquarie University, Sydney, Australia
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  • Carolyn M. Sue MBBS, PhD, FRACP,

    1. Department of Neurology, Royal North Shore Hospital, Sydney, Australia
    2. Sydney Medical School, University of Sydney, Sydney, Australia
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  • Michael W. Hayes MA, MSc, MBBS, FRACP,

    1. Sydney Medical School, University of Sydney, Sydney, Australia
    2. Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia
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  • Lisbeth Tranebjærg MD, PhD,

    1. Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine; The Panum Institute, University of Copenhagen, Copenhagen, Denmark
    2. Department of Audiology, H:S Bispebjerg Hospital, Copenhagen, Denmark
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  • Victor S.C. Fung MBBS, PhD, FRACP

    Corresponding author
    1. Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia
    2. Sydney Medical School, University of Sydney, Sydney, Australia
    • Movement Disorders Unit, Department of Neurology, Westmead Hospital, Westmead, NSW 2145, Australia
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  • Ainhi D. Ha and Kaitlyn L. Parratt contributed equally to this article.

  • Funding agencies: The Lundbeck Foundation (grant no. 32011) and Widex AS provided financial support to the Audiogenetic Research Group at ICMM. The molecular studies took place at the Wilhelm Johannsen Centre for Functional Genome Research, which was established by grants from the National Research Foundation in Denmark.

  • §

    Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Mohr–Tranebjaerg syndrome (MTS) is an X-linked recessive disorder characterized by deafness and dystonia. However the phenotypic expression of dystonia has not been systematically defined. We report clinical, neurophysiological, and ophthalmological data on 6 subjects from 3 Australian kindreds, including 2 with novel mutations, together with a systematic review of the literature, in order to define the phenotypic expression of dystonia. Profound hearing impairment in affected males develops by infancy and precedes the development of dystonia, which varies in time of onset from the first to the sixth decades, with a peak in the second and third decades. Dystonia in MTS tends to be focal, segmental, or multifocal in distribution at onset, with a predilection for the upper body, variably involving the head, neck, and upper limbs. The majority of patients have progression or generalization of their dystonia regardless of age of onset. Within our 3 kindreds, we observed relative intrafamilial homogeneity but interfamilial variation. The median time to the development of moderate-severely disabling dystonia in these subjects was 11 years. Associated features included progressive cognitive decline, pyramidal signs, and in 1 patient, gait freezing and postural instability. Optic atrophy and cortical visual impairment were both observed. We report for the first time a female patient who developed multiple disabling neurological complications of MTS. Our findings more clearly define and expand the phenotype of both the dystonia and other neurological features of MTS and have implications for the diagnosis and management of this condition. © 2012 Movement Disorder Society

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