{"doi":"10.1002/mds.28807","title":"Dissecting the Phenotype and Genotype of <scp><i>PLA2G6</i></scp>‐Related Parkinsonism","abstract":"BACKGROUND: Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration. OBJECTIVES: The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported. METHODS: We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review. RESULTS: PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) 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-four PLA2G6 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- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology. CONCLUSIONS: Biallelic PLA2G6 mutations cause early-onset 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-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2021,"id":155382,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":657490,"name":"Sahil Mehta","orcid":"0000-0002-5915-8334","position":1,"is_corresponding":false},{"id":657491,"name":"Giulia Di Lazzaro","orcid":"0000-0003-2413-1788","position":2,"is_corresponding":false},{"id":567329,"name":"Anna Latorre","orcid":"0000-0001-7103-5209","position":3,"is_corresponding":false},{"id":255820,"name":"Mark J. Edwards","orcid":"0000-0002-8283-9015","position":4,"is_corresponding":false},{"id":657492,"name":"Bettina Balint","orcid":"0000-0003-4127-8554","position":5,"is_corresponding":false},{"id":657493,"name":"Purba Basu","orcid":"0009-0009-3383-3264","position":6,"is_corresponding":false},{"id":271296,"name":"Christopher Kobylecki","orcid":"0000-0002-7797-0756","position":7,"is_corresponding":false},{"id":405057,"name":"Sergiu Groppa","orcid":"0000-0002-2551-5655","position":8,"is_corresponding":false},{"id":657494,"name":"Anaita Hegde","orcid":"0000-0003-3471-9876","position":9,"is_corresponding":false},{"id":657495,"name":"Eoin Mulroy","orcid":"0000-0003-3057-0592","position":10,"is_corresponding":false},{"id":657496,"name":"Carlos Estevez‐Fraga","orcid":"0000-0001-6855-1093","position":11,"is_corresponding":false},{"id":657986,"name":"Anshita Arora","orcid":null,"position":12,"is_corresponding":false},{"id":657497,"name":"Hrishikesh Kumar","orcid":"0000-0002-9789-7832","position":13,"is_corresponding":false},{"id":657498,"name":"Susanne A. 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