The syndrome of deafness-dystonia: Clinical and genetic heterogeneity

Maja Kojovic, Isabel Pareés, Tania Lampreia, Karolina Pienczk-Reclawowicz, Georgia Xiromerisiou, Ignacio Rubio-Agusti, Milica Kramberger, Miryam Carecchio, Anas M. Alazami, Francesco Brancati, Jaroslaw Slawek, Zvezdan Pirtosek, Enza Maria Valente, Fowzan S. Alkuraya, Mark J. Edwards, Kailash P. Bhatia

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)795-803
Number of pages9
JournalMovement Disorders
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Deafness-dystonia syndrome
  • Mitochondrial disorders
  • Mohr-Tranebjaerg syndrome
  • Woodhouse-Sakati syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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