{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:19:51Z","timestamp":1791825591488,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Complex parkinsonism is the commonest phenotype in late\u2010onset <jats:italic>PLA2G6<\/jats:italic>\u2010associated neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to deeply characterize phenogenotypically <jats:italic>PLA2G6<\/jats:italic>\u2010related parkinsonism in the largest cohort ever reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report 14 new cases of <jats:italic>PLA2G6<\/jats:italic>\u2010related parkinsonism and perform a systematic literature review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>PLA2G6<\/jats:italic>\u2010related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0\u2009years) with parkinsonism\/dystonia, gait\/balance, and\/or psychiatric\/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and\/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty\u2010four <jats:italic>PLA2G6<\/jats:italic> mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood\u2010 and late\u2010onset <jats:italic>PLA2G6<\/jats:italic>\u2010associated neurodegeneration. In five deceased patients, median disease duration was 13.0\u2009years. Brain pathology in three cases showed mixed Lewy and tau pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Biallelic <jats:italic>PLA2G6<\/jats:italic> mutations cause early\u2010onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro\/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell\u2010tale sign. \u00a9 2021 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.28807","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T04:14:51Z","timestamp":1633839291000},"page":"148-161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Dissecting the Phenotype and Genotype of <scp><i>PLA2G6<\/i><\/scp>\u2010Related Parkinsonism"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4706-6245","authenticated-orcid":false,"given":"Francesca","family":"Magrinelli","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology University College London  London United 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