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A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset\u2009&lt;\u200912\u00a0years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11\/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8\/50 (16%)<jats:italic>.<\/jats:italic> Missense pathogenic variants in <jats:italic>SPAST<\/jats:italic> were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional <jats:italic>Spastic Paraplegia Rating Scale<\/jats:italic> progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.<\/jats:p>","DOI":"10.1038\/s41598-021-01635-2","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T11:03:36Z","timestamp":1636974216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias"],"prefix":"10.1038","volume":"11","author":[{"given":"Gabriela Marchisio","family":"Giordani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcio","family":"Diniz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Fussiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carelis","family":"Gonzalez-Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Carvalho","family":"Donis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Freua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Paiva Magalh\u00e3es","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian Let\u00edcia","family":"de Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orlando Graziani Povoas","family":"Barsottini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Rosemberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luiz","family":"Pedroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Marcondes Cavalcante","family":"Fran\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas Alex Morales","family":"Saute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"issue":"7","key":"1635_CR1","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1007\/s00415-014-7598-y","volume":"262","author":"A Hensiek","year":"2015","unstructured":"Hensiek, A., Kirker, S. & Reid, E. 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