Funding agencies: This work was been funded by the Italian Ministry of Health (Ricerca Corrente 2012).
The syndrome of deafness-dystonia: Clinical and genetic heterogeneity
Version of Record online: 15 FEB 2013
Copyright © 2013 Movement Disorder Society
Volume 28, Issue 6, pages 795–803, June 2013
How to Cite
Kojovic, M., Pareés, I., Lampreia, T., Pienczk-Reclawowicz, K., Xiromerisiou, G., Rubio-Agusti, I., Kramberger, M., Carecchio, M., Alazami, A. M., Brancati, F., Slawek, J., Pirtosek, Z., Valente, E. M., Alkuraya, F. S., Edwards, M. J. and Bhatia, K. P. (2013), The syndrome of deafness-dystonia: Clinical and genetic heterogeneity. Mov. Disord., 28: 795–803. doi: 10.1002/mds.25394
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.
- Issue online: 25 JUN 2013
- Version of Record online: 15 FEB 2013
- Manuscript Accepted: 15 JAN 2013
- Manuscript Revised: 27 DEC 2012
- Manuscript Received: 28 OCT 2012
- deafness-dystonia syndrome;
- Mohr-Tranebjaerg syndrome;
- Woodhouse-Sakati syndrome;
- mitochondrial disorders
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