AUTHOR=Lowe Simon A. TITLE=Critical developmental periods of vulnerability in dystonia JOURNAL=Dystonia VOLUME=3 YEAR=2024 URL=https://www.frontierspartnerships.org/journals/dystonia/articles/10.3389/dyst.2024.12125 DOI=10.3389/dyst.2024.12125 ISSN=2813-2106 ABSTRACT=

Dystonia is a heterogenous movement disorder characterised by involuntary muscle contractions, leading to abnormal postures and movements. Despite being the third most common movement disorder, the pathophysiological mechanisms causing dystonia are incompletely understood. Isolated dystonia is often caused by pathogenic mutations in single genes. An emerging body of evidence suggests that at least some forms of isolated dystonia have a strong developmental component, with pathogenic effects acting within discrete periods of increased vulnerability during neurodevelopment. The extent to which this is a common feature of genetically distinct forms of dystonia, and which developmental mechanisms might be disrupted during these periods, remains unclear. During critical periods of development, neuronal activity is instructive in the maturation of neuronal circuits, and inappropriate levels of activity during this period can lead to permanent defects. This review, with an intentional focus on our work, outlines evidence implicating disruptions to neuronal activity during critical developmental periods as a potential mechanism underlying inherited motor disorders in general, and dystonia in particular.