The phenotypic spectrum of dystonia in Mohr-Tranebjaerg syndrome

Mov Disord. 2012 Jul;27(8):1034-40. doi: 10.1002/mds.25033. Epub 2012 Jun 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Australia
  • Child
  • Child, Preschool
  • Cognition Disorders / etiology
  • Deaf-Blind Disorders / genetics*
  • Deaf-Blind Disorders / physiopathology*
  • Deaf-Blind Disorders / psychology
  • Disease Progression
  • Dystonia / genetics*
  • Dystonia / physiopathology*
  • Dystonia / psychology
  • Evoked Potentials, Somatosensory
  • Evoked Potentials, Visual
  • Exons
  • Female
  • Humans
  • Infant
  • Intellectual Disability / etiology
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology*
  • Intellectual Disability / psychology
  • Introns
  • Magnetic Resonance Imaging
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mutation
  • Neuropsychological Tests
  • Optic Atrophy / genetics*
  • Optic Atrophy / physiopathology*
  • Optic Atrophy / psychology
  • Pedigree
  • Sex Characteristics
  • Young Adult

Substances

  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TIMM8A protein, human

Supplementary concepts

  • Mohr-Tranebjaerg syndrome