The syndrome of deafness-dystonia: clinical and genetic heterogeneity.

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.

• Authors: 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
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 28 Issue 6 Pg. 795-803 (Jun 2013) ISSN: 1531-8257 [Electronic] United States
• PMID: 23418071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Movement Disorder Society.

Chemical References

• 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

Topics

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