Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.
J Neural Transm (Vienna). 2021 Apr;128(4):417-429. doi: 10.1007/s00702-020-02269-w. Epub 2020 Oct 24.
The genetic combined dystonias are a clinically and genetically heterogeneous group of neurologic disorders defined by the overlap of dystonia and other movement disorders such as parkinsonism or myoclonus. The number of genes associated with combined dystonia syndromes has been increasing due to the wider recognition of clinical features and broader use of genetic testing. Nevertheless, these diseases are still rare and represent only a small subgroup among all dystonias. Dopa-responsive dystonia (DYT/PARK-GCH1), rapid-onset dystonia-parkinsonism (DYT/PARK-ATP1A3), X-linked dystonia-parkinsonism (XDP, DYT/PARK-TAF1), and young-onset dystonia-parkinsonism (DYT/PARK-PRKRA) are monogenic combined dystonias accompanied by parkinsonian features. Meanwhile, MYC/DYT-SGCE and MYC/DYT-KCTD17 are characterized by dystonia in combination with myoclonus. In the past, common molecular pathways between these syndromes were the center of interest. Although the encoded proteins rather affect diverse cellular functions, recent neurophysiological evidence suggests similarities in the underlying mechanism in a subset. This review summarizes recent developments in the combined dystonias, focusing on clinico-genetic features and neurophysiologic findings. Disease-modifying therapies remain unavailable to date; an overview of symptomatic therapies for these disorders is also presented.
遗传性共病性肌张力障碍是一组临床表现和遗传学具有异质性的神经系统疾病，其特征是存在肌张力障碍与其他运动障碍（如帕金森病或肌阵挛）的重叠。由于对临床特征的认识越来越广泛，以及遗传检测的应用越来越广泛，与共病性肌张力障碍综合征相关的基因数量不断增加。尽管如此，这些疾病仍然很少见，仅占所有肌张力障碍患者的一小部分。多巴反应性肌张力障碍（DYT/PARK-GCH1）、发作性肌张力障碍帕金森病（DYT/PARK-ATP1A3）、X 连锁肌张力障碍帕金森病（XDP，DYT/PARK-TAF1）和早发性肌张力障碍帕金森病（DYT/PARK-PRKRA）是伴有帕金森病特征的单基因共病性肌张力障碍。同时，MYC/DYT-SGCE 和 MYC/DYT-KCTD17 的特征是肌张力障碍与肌阵挛相结合。过去，这些综合征之间的共同分子途径是研究的重点。尽管编码的蛋白质对不同的细胞功能有影响，但最近的神经生理学证据表明，在一个亚组中，其潜在机制存在相似性。本文综述了共病性肌张力障碍的最新进展，重点介绍了临床遗传学特征和神经生理学发现。目前还没有针对这些疾病的治疗方法，因此本文也概述了这些疾病的对症治疗方法。
