title: 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: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, United Kingdom.
authors: Maja
authors: M
authors: Kojovic
authors: Isabel
authors: I
authors: Pareés
authors: Tania
authors: T
authors: Lampreia
authors: Karolina
authors: K
authors: Pienczk-Reclawowicz
authors: Georgia
authors: G
authors: Xiromerisiou
authors: Ignacio
authors: I
authors: Rubio-Agusti
authors: Milica
authors: M
authors: Kramberger
authors: Miryam
authors: M
authors: Carecchio
authors: Anas M
authors: AM
authors: Alazami
authors: Francesco
authors: F
authors: Brancati
authors: Jaroslaw
authors: J
authors: Slawek
authors: Zvezdan
authors: Z
authors: Pirtosek
authors: Enza Maria
authors: EM
authors: Valente
authors: Fowzan S
authors: FS
authors: Alkuraya
authors: Mark J
authors: MJ
authors: Edwards
authors: Kailash P
authors: KP
authors: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D054062:Deaf-Blind Disorders / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D004421:Dystonia / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics*; D017907:Leviviridae; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009896:Optic Atrophy / Q000209:etiology / Q000235:genetics*; D012189:Retrospective Studies; D043743:Ubiquitin-Protein Ligase Complexes; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C556016:DCAF17 protein, human; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human; C118122:TIMM8A protein, human; D043743:Ubiquitin-Protein Ligase Complexes