{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:48:17Z","timestamp":1789861697083,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB936"],"award-info":[{"award-number":["SFB936"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB TR134 C1"],"award-info":[{"award-number":["SFB TR134 C1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1957"],"award-info":[{"award-number":["GRK1957"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease\u2010modifying therapies at a time point where progressive neurodegeneration can still be modified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this study was to determine whether motor or non\u2010motor signs of the disease occur as indicators of a prodromal phase of X\u2010linked dystonia\u2010parkinsonism (XDP), a highly\u2010penetrant monogenic movement disorder with striking basal ganglia pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In addition to a comprehensive clinical assessment, sensor\u2010based balance and gait analyses were performed in non\u2010manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient\u2010boosted trees (GBT) methodology was utilized to classify groups of interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best\u2010performing GBT\u2010based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29033","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T04:25:14Z","timestamp":1651465514000},"page":"1474-1482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Prodromal X\u2010Linked Dystonia\u2010Parkinsonism is Characterized by a Subclinical Motor Phenotype"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-8112","authenticated-orcid":false,"given":"Julia","family":"Steinhardt","sequence":"first","affiliation":[{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Heldmann","sequence":"additional","affiliation":[{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-7911","authenticated-orcid":false,"given":"Andreas","family":"Sprenger","sequence":"additional","affiliation":[{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck 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