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Thomsen, M.* ; Lange, L.M.* ; Zech, M. ; Lohmann, K.*

Genetics and pathogenesis of dystonia.

Annu. Rev. Pathol.-Mech. Dis. 19, 99-131 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or intermittent muscle contractions. A number of groundbreaking genetic and molecular insights have recently been gained. While they enable genetic testing and counseling, their translation into new therapies is still limited. However, we are beginning to understand shared pathophysiological pathways and molecular mechanisms. It has become clear that dystonia results from a dysfunctional network involving the basal ganglia, cerebellum, thalamus, and cortex. On the molecular level, more than a handful of, often intertwined, pathways have been linked to pathogenic variants in dystonia genes, including gene transcription during neurodevelopment (e.g., KMT2B, THAP1), calcium homeostasis (e.g., ANO3, HPCA), striatal dopamine signaling (e.g., GNAL), endoplasmic reticulum stress response (e.g., EIF2AK2, PRKRA, TOR1A), autophagy (e.g., VPS16), and others. Thus, different forms of dystonia can be molecularly grouped, which may facilitate treatment development in the future. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 19 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Dystonia ; Genetics ; Molecular Pathways ; Pathophysiology; Movement-disorders; Myoclonus-dystonia; Basal Ganglia; Intellectual Disability; 3-nitropropionic Acid; Nuclear-envelope; Dyt1 Dystonia; Cell Biology; Taf1 Gene; Mutations
ISSN (print) / ISBN 1553-4006
e-ISSN 1553-4014
Journal Annual Review of Pathology: Mechanisms of Disease
Quellenangaben Volume: 19, Issue: , Pages: 99-131 Article Number: , Supplement: ,
Publisher Annual Reviews
Publishing Place 4139 El Camino Way, Po Box 10139, Palo Alto, Ca 94303-0139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Grants German Research Foundation
PreDYT by the European Joint Programme on Rare Diseases (Joint Transnational Call 2022)
German Federal Ministry of Education and Research
Bachmann-Strauss Dystonia & Parkinson's Foundation