{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:22:08Z","timestamp":1792642928022,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2026,8]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by progressive spasticity and lower limb weakness. The most common forms of autosomal dominant HSP are caused by pathogenic variants in\n SPAST<\/jats:italic>\n (SPG4 or HSP\u2010\n SPAST<\/jats:italic>\n ),\n ATL1<\/jats:italic>\n (SPG3A or HSP\u2010\n ATL1<\/jats:italic>\n ), and\n REEP1<\/jats:italic>\n (SPG31 or HSP\u2010\n REEP1<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n We performed an MDSGene Systematic Review to determine in\u2010depth genotype\u2013phenotype associations and to estimate longitudinal progression, to inform prognostication and clinical trial stratification.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We systematically collected demographic, phenotypic, and genetic data from published reports of individuals affected by these forms of HSP using the MDSGene protocol.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We reviewed 2177 affected individuals, including 1670 individuals with HSP\u2010\n SPAST<\/jats:italic>\n , 356 with HSP\u2010\n ATL1<\/jats:italic>\n and 151 with HSP\u2010\n REEP1<\/jats:italic>\n . HSP\u2010\n ATL1<\/jats:italic>\n was associated with an earlier age at onset compared to HSP\u2010\n SPAST<\/jats:italic>\n and HSP\u2010\n REEP1<\/jats:italic>\n . Toe\u2010walking was more frequently reported in HSP\u2010\n ATL1<\/jats:italic>\n (10.4%) and HSP\u2010\n REEP1<\/jats:italic>\n (3.3%) than HSP\u2010\n SPAST<\/jats:italic>\n (0.3%). Upper limb hyperreflexia and abnormalities of bladder function were more frequent in HSP\u2010\n SPAST<\/jats:italic>\n than HSP\u2010\n ATL1<\/jats:italic>\n or HSP\u2010\n REEP1<\/jats:italic>\n . Sufficient data was available to estimate disease progression for HSP\u2010\n SPAST<\/jats:italic>\n ; this showed that Spastic Paraplegia Rating Scale (SPRS) scores increased with increasing age at examination after the age of 40\u2009years. Truncating variants were more frequent in HSP\u2010\n SPAST<\/jats:italic>\n and HSP\u2010\n REEP1<\/jats:italic>\n than HSP\u2010\n ATL1<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Overall, HSP\u2010\n ATL1<\/jats:italic>\n , HSP\u2010\n SPAST<\/jats:italic>\n and HSP\u2010\n REEP1<\/jats:italic>\n demonstrated differences in clinical phenotypes. To our knowledge, this is the first systematic review to model longitudinal progression using SPRS scores in HSP. Missing data is a limiting factor in all these comparisons, highlighting the need for uniform data collection. Online resources can be found at\n https:\/\/www.mdsgene.org\/<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mdc3.70559","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:09:37Z","timestamp":1772989777000},"page":"1804-1814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MDSGene<\/scp>\n Systematic Review of Common Forms of Dominant Hereditary Spastic Paraplegia: Novel Insights"],"prefix":"10.1002","volume":"13","author":[{"given":"Ce","family":"Kang","sequence":"first","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health University of Sydney Camperdown NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasumi","family":"Rajalingam","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"},{"name":"Department of Psychiatry Western Michigan University Homer Stryker M.D. School of Medicine Kalamazoo MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Walls","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Information Technologies University of Sydney Darlington NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Huang","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sun","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-319X","authenticated-orcid":false,"given":"Laura I.","family":"Rudaks","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health University of Sydney Camperdown NSW Australia"},{"name":"ANZAC Research Institute Department of Neurology and Molecular Medicine Laboratory, Concord Repatriation General Hospital and Sydney Local Health District Concord NSW Australia"},{"name":"Translational Neurogenomics Group Garvan Institute for Medical Research Darlinghurst NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-7007","authenticated-orcid":false,"given":"Dennis","family":"Yeow","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health University of Sydney Camperdown NSW Australia"},{"name":"ANZAC Research Institute Department of Neurology and Molecular Medicine Laboratory, Concord Repatriation General Hospital and Sydney Local Health District Concord NSW Australia"},{"name":"Translational Neurogenomics Group Garvan Institute for Medical Research Darlinghurst NSW Australia"},{"name":"Neuroscience Research Australia and Faculty of Medicine and Health University of New South Wales Sydney NSW Australia"},{"name":"Department of Neurology Prince of Wales Hospital, South Eastern Sydney Local Health District Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashar","family":"Rasheed","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny W.","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moath","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Neurology NYP Brooklyn Methodist Hospital Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-7941","authenticated-orcid":false,"given":"Marianthi","family":"Breza","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit 1st Department of Neurology Eginition Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susen","family":"Schaake","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Vekhande","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology) and Medical Genetics Faculty of Medicine and Dentistry University of Alberta Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn E.","family":"Massa","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakash","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology) and Medical Genetics Faculty of Medicine and Dentistry University of Alberta Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Sue","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia and Faculty of Medicine and Health University of New South Wales Sydney NSW Australia"},{"name":"Department of Neurology Prince of Wales Hospital, South Eastern Sydney Local Health District Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Cambi","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Suchowersky","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology) and Medical Genetics Faculty of Medicine and Dentistry University of Alberta Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Vulinovic","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Petkovic","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9236-9328","authenticated-orcid":false,"given":"Connie","family":"Marras","sequence":"additional","affiliation":[{"name":"The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-6962","authenticated-orcid":false,"given":"Kishore R.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health University of Sydney Camperdown NSW Australia"},{"name":"ANZAC Research Institute Department of Neurology and Molecular Medicine Laboratory, Concord Repatriation General Hospital and Sydney Local Health District Concord NSW Australia"},{"name":"Translational Neurogenomics Group Garvan Institute for Medical Research Darlinghurst NSW Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, St Vincent's Healthcare Clinical Campus University of New South Wales Darlinghurst NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12184"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-021-01099-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28982"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.06.011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"e_1_2_9_7_1","volume-title":"GeneReviews((R))","author":"Hedera P","year":"1993"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09633-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-017-0079-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27352"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27527"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28874"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228242.53336.90"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26651"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy285"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn026"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.03.043"},{"key":"e_1_2_9_20_1","volume-title":"GeneReviews((R))","author":"Hedera P","year":"1993"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac072"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11030403"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21114"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000244413.49258.f5"}],"container-title":["Movement Disorders Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mdc3.70559","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mdc3.70559","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mdc3.70559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T08:36:26Z","timestamp":1786782986000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mdc3.70559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/mdc3.70559"],"URL":"https:\/\/doi.org\/10.1002\/mdc3.70559","archive":["Portico"],"relation":{},"ISSN":["2330-1619","2330-1619"],"issn-type":[{"value":"2330-1619","type":"print"},{"value":"2330-1619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"2025-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}