{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:11:35Z","timestamp":1792131095371,"version":"4.4.0"},"reference-count":140,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RF19.12"],"award-info":[{"award-number":["RF19.12"]}]},{"name":"Department of Medicine and Surgery of the University of Perugia","award":["DSCH_BASE19_ORLACCHIO"],"award-info":[{"award-number":["DSCH_BASE19_ORLACCHIO"]}]},{"name":"Department of Medicine and Surgery of the University of Perugia","award":["RICERCABASE_2020_ORLACCHIO"],"award-info":[{"award-number":["RICERCABASE_2020_ORLACCHIO"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder with the predominant clinical manifestation of spasticity in the lower extremities. HSP is categorised based on inheritance, the phenotypic characters, and the mode of molecular pathophysiology, with frequent degeneration in the axon of cervical and thoracic spinal cord\u2019s lateral region, comprising the corticospinal routes. The prevalence ranges from 0.1 to 9.6 subjects per 100,000 reported around the globe. Though modern medical interventions help recognize and manage the disorder, the symptomatic measures remain below satisfaction. The present review assimilates the available data on HSP and lists down the chromosomes involved in its pathophysiology and the mutations observed in the respective genes on the chromosomes. It also sheds light on the treatment available along with the oral\/intrathecal medications, physical therapies, and surgical interventions. Finally, we have discussed the related diagnostic techniques as well as the linked pharmacogenomics studies under future perspectives.<\/jats:p>","DOI":"10.3390\/ijms23031697","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T09:59:21Z","timestamp":1643709561000},"page":"1697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":172,"title":["Hereditary Spastic Paraplegia: An Update"],"prefix":"10.3390","volume":"23","author":[{"given":"Arun","family":"Meyyazhagan","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 di Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2602-3281","authenticated-orcid":false,"given":"Antonio","family":"Orlacchio","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 di Perugia, 06132 Perugia, Italy"},{"name":"Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, 00143 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S1474-4422(19)30235-2","article-title":"Hereditary spastic paraplegia: From diagnosis to emerging therapeutic approaches","volume":"18","author":"Shribman","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635032","DOI":"10.3389\/fneur.2021.635032","article-title":"Muscle characteristics in pediatric hereditary spastic paraplegia vs. bilateral spastic cerebral palsy: An exploratory study","volume":"12","author":"Hanssen","year":"2021","journal-title":"Front. 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