TY - JOUR
T1 - The syndrome of deafness-dystonia
T2 - Clinical and genetic heterogeneity
AU - Kojovic, Maja
AU - Pareés, Isabel
AU - Lampreia, Tania
AU - Pienczk-Reclawowicz, Karolina
AU - Xiromerisiou, Georgia
AU - Rubio-Agusti, Ignacio
AU - Kramberger, Milica
AU - Carecchio, Miryam
AU - Alazami, Anas M.
AU - Brancati, Francesco
AU - Slawek, Jaroslaw
AU - Pirtosek, Zvezdan
AU - Valente, Enza Maria
AU - Alkuraya, Fowzan S.
AU - Edwards, Mark J.
AU - Bhatia, Kailash P.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Deafness-dystonia syndrome
KW - Mitochondrial disorders
KW - Mohr-Tranebjaerg syndrome
KW - Woodhouse-Sakati syndrome
UR - http://www.scopus.com/inward/record.url?scp=84879604371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879604371&partnerID=8YFLogxK
U2 - 10.1002/mds.25394
DO - 10.1002/mds.25394
M3 - Article
C2 - 23418071
AN - SCOPUS:84879604371
VL - 28
SP - 795
EP - 803
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 6
ER -