Combined dystonias: clinical and genetic updates
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NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - REVIEW ARTICLE
Combined dystonias: clinical and genetic updates Anne Weissbach1,2 · Gerard Saranza3 · Aloysius Domingo4,5 Received: 8 September 2020 / Accepted: 9 October 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract 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. Keywords Dystonia · Parkinsonism · GCH1 · ATP1A3 · X-linked dystonia-parkinsonism · Myoclonus-dystonia
Introduction The monogenic combined dystonias are a heterogeneous group of disorders where another movement disorder accompanies dystonia. In 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
* Aloysius Domingo [email protected] 1
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
2
Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
3
Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, ON, Canada
4
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
5
Collaborative Center for X‑Linked Dystonia‑Parkinsonism, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
(DYT/PARK-PRKRA), the dystonia is accompanied by parkinsonian features. Apart from having combined dystonia and parkinsonism as the phenotype, these disorders share little in common in genetics or molecular mechanisms. In MYC/DYT-SGCE and MYC/DYT-KCTD17, dystonia occurs in combination with myoclonus, and in the former, the majority of patients have psychiatric comorbid
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