The syndrome of deafness-dystonia: clinical and genetic heterogeneity

Mov Disord. 2013 Jun;28(6):795-803. doi: 10.1002/mds.25394. Epub 2013 Feb 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Apoptosis Regulatory Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Deaf-Blind Disorders / etiology
  • Deaf-Blind Disorders / genetics*
  • Disease Progression
  • Dystonia / etiology
  • Dystonia / genetics*
  • Family Health
  • Female
  • Genetic Heterogeneity*
  • Genetic Testing
  • Humans
  • Intellectual Disability / etiology
  • Intellectual Disability / genetics*
  • Leviviridae
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Optic Atrophy / etiology
  • Optic Atrophy / genetics*
  • Retrospective Studies
  • Ubiquitin-Protein Ligase Complexes
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • DCAF17 protein, human
  • DNA-Binding Proteins
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Nuclear Proteins
  • THAP1 protein, human
  • TIMM8A protein, human
  • Ubiquitin-Protein Ligase Complexes

Supplementary concepts

  • Mohr-Tranebjaerg syndrome