Clinical and radiological features in patients with DYT6 dystonia

Objective To summarize the clinical and radiological features of DYT6 dystonia with mutations based on the data of our patient cohort as well as the report by others. Methods Clinical data of the 11 patients with DYT6 dystonia in Peking Union Medical College Hospital from June 2009 to May 2012 were retrospectively reviewed and analyzed.Clinical data included gender，onset age，initiative symptom of onset，the sites of involvemet，family history，etc.All patients were examined for brain MRI scan，6 patients were examined for DTI. Results Of the eleven geneconfirmed DYT6 dystonia patients，7 were male and 4 were female，with an onset-age ranged from 5 years to 36 years，the mean age of onset was 19.4 years.Eight patients had a family history.There were 10 patients with early onset dystonia and only 1 patient with late onset dystonia.The most common site of onset was the neck (7/11)，and the next was the right arm，1-5 body areas were affected at the time of neurological assessment，the average amount was 2.8，and the most frequently affected anatomical site was the neck (10/11)，next came lower face，jaw and tongue.Among all the patients，6 patients presented with segmental dystonia，4 patients presented with focal dystonia，only 1 patient presented with generalized dystonia.All the patients with thanatos-associated protein domain-containing apoptosis-associated protein (THAP) domain affected had a family history，but the patients with the same mutant gene varied with clinical manifestation.Only 1 patients with non-THAP domain affected had a family history，but in most families，there were adult asymptomatic mutant gene carriers.Mutations within the THAP domain were associated with an earlier age of onset than non-THAP domain (17.3 and 21.8 years old).Routine MRI of all patients were normal and DTI of 6 patients showed that fractional anisotropy values in the bilateral sensorimotor area in DYT6 dystonia were reduced.A detailed description of a patient with TOR1A and THAP1 gene mutations was given. Conclusions Early onset dystonia is the main manifestation in patients with DYT6 dystonia in China.The most common site of onset is the neck，and the next is the right arm.The most frequently affected anatomical site is the neck，next come lower face，jaw and tongue.Laryngeal dystonia is absent.The patients with same mutant gene show high heterogeneity in the clinical manifestations，mutations within the THAP domain of THAP1 tend to manifest at an earlier age and higher penetration than mutations localized to non-THAP domain.Reduction of fractional anisotropy values indicates that the axonal integrity and coherence in the region of sensorimotor area is damaged in DYT6 dystonia. Key words: Dystonia; DNA-binding proteins; Nuclear proteins; Apoptosis regulatory proteins; Mutation; Magnetic resonance imaging