Get access

The syndrome of deafness-dystonia: Clinical and genetic heterogeneity

Authors

  • Maja Kojovic MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Department of Neurology, University of Ljubljana, Ljubljana, Slovenia
    Search for more papers by this author
  • Isabel Pareés MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    Search for more papers by this author
  • Tania Lampreia MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
    Search for more papers by this author
  • Karolina Pienczk-Reclawowicz MD,

    1. Developmental Neurology Department, Medical University of Gdansk, Poland
    Search for more papers by this author
  • Georgia Xiromerisiou MD, PhD,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, Queen Square, London, United Kingdom
    2. Department of Neurology, Papageorgiou General Hospital, Thessaloniki, Greece
    Search for more papers by this author
  • Ignacio Rubio-Agusti MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Movement Disorders Unit, Neurology Department, Hospital Universitario La Fe, Valencia, Spain
    Search for more papers by this author
  • Milica Kramberger MD, PhD,

    1. Department of Neurology, University of Ljubljana, Ljubljana, Slovenia
    Search for more papers by this author
  • Miryam Carecchio MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    2. Department of Neurology, Amedeo Avogadro University, Novara, Italy
    Search for more papers by this author
  • Anas M. Alazami MD, PhD,

    1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    Search for more papers by this author
  • Francesco Brancati MD, PhD,

    1. Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy
    2. Department of Medical, Oral, and Biotechnological Sciences, Gabriele D'Annunzio University, Chieti, Italy
    Search for more papers by this author
  • Jaroslaw Slawek MD, PhD,

    1. Department of Neurological-Psychiatric Nursing, Medical University of Gdansk and Department of Neurology and Stroke, St. Adalbert Hospital, Gdansk, Poland
    Search for more papers by this author
  • Zvezdan Pirtosek MD, PhD,

    1. Department of Neurology, University of Ljubljana, Ljubljana, Slovenia
    Search for more papers by this author
  • Enza Maria Valente MD, PhD,

    1. Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Laboratory, San Giovanni Rotondo, Italy
    2. Department of Drug and Health Products Sciences, University of Messina, Messina, Italy
    Search for more papers by this author
  • Fowzan S. Alkuraya MD, PhD,

    1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    2. Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
    3. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
    Search for more papers by this author
  • Mark J. Edwards MD, PhD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    Search for more papers by this author
  • Kailash P. Bhatia MD

    Corresponding author
    1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom
    • Correspondence to: Prof. Bhatia, Sobell Department, Institute of Neurology, UCL, Queen Square, London WC1N 3BG; k.bhatia@ucl.ac.uk

    Search for more papers by this author

  • Funding agencies: This work was been funded by the Italian Ministry of Health (Ricerca Corrente 2012).

  • 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

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions. © 2013 Movement Disorder Society

Ancillary