{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:09:29Z","timestamp":1784214569597,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":118,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Case Reports in Neurological Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>SPAST<\/jats:italic>\n                      gene encodes spastin, a microtubule\u2010severing protein. Pathogenic variants in this gene are commonly associated with autosomal dominant Spastic paraplegia type 4 (\n                      <jats:italic>SPG4<\/jats:italic>\n                      ), a neurodegenerative disorder presenting with progressive lower limb spasticity. Severe phenotypes involving more extensive neurological impairment are rare.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>\n                      We report the first known case of an adolescent with a rare pathogenic\n                      <jats:italic>SPAST<\/jats:italic>\n                      variant (NM_014946.4: c.1507C\u2009&gt;\u2009T; NP_055761.2: p. [Arg503Trp]) presenting with spastic quadriplegia. Additional features included severe intellectual disability, absent speech, dysphagia, and epilepsy, manifestations infrequently reported in association with\n                      <jats:italic>SPAST<\/jats:italic>\n                      mutations. He was born prematurely at 32\u2009weeks of gestation after a complicated antenatal period due to the development of preeclampsia at 23\u2009weeks and gestational diabetes mellitus at 26\u2009weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The patient\u2019s clinical presentation represents one of the most severe phenotypes described in the literature for\n                      <jats:italic>SPAST<\/jats:italic>\n                      \u2010related disorders. The identification of a genetic cause provided a more satisfactory and specific diagnosis than the previously presumed etiology of perinatal asphyxia. This case broadens the phenotypic spectrum of\n                      <jats:italic>SPAST<\/jats:italic>\n                      \u2010related disease and highlights the role of genetic testing in the diagnostic workup of complex neurological conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We report the first case of a pathogenic variant in the\n                      <jats:italic>SPAST<\/jats:italic>\n                      gene and quadriplegia and one of the most severe clinical phenotypes described in the literature in association with variants in this gene. This report underscores the importance of considering\n                      <jats:italic>SPAST<\/jats:italic>\n                      mutations in patients with atypical or severe neurodevelopmental presentations. Genetic diagnosis enables more accurate prognosis, individualized medical care, and appropriate genetic counseling for families.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/crnm\/2632593","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:21:06Z","timestamp":1777450866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spastic Quadriplegia Resulting From a Pathogenic Variant in the\n                    <i>SPAST<\/i>\n                    Gene: A First Report"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-7537","authenticated-orcid":false,"given":"Eirini","family":"Kostopoulou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-0212","authenticated-orcid":false,"given":"Maria","family":"Lagadinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ageliki","family":"Karatza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xenophon","family":"Sinopidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8517-133X","authenticated-orcid":false,"given":"Rin","family":"Khang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7929-1573","authenticated-orcid":false,"given":"Gabriel","family":"Dimitriou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1135-8"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282f1cde0"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/15472"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29225"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2017.03.001"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228245.19556.fa"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.9.1569"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.5.1487"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.64.1.61"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000022798"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200185"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000108629.04434.05"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3181b04c6c"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.55.1.89"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.6.849"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000125324.32082.d9"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073818756680"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14510"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.11.007"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2007.02.003"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1694973"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073816639718"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00847-4"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000223315.62404.00"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000294330.27058.61"}],"container-title":["Case Reports in Neurological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crnm\/2632593","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/crnm\/2632593","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crnm\/2632593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:50:27Z","timestamp":1784213427000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/crnm\/2632593"}},"subtitle":[],"editor":[{"given":"Isabella Laura","family":"Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/crnm\/2632593"],"URL":"https:\/\/doi.org\/10.1155\/crnm\/2632593","archive":["Portico"],"relation":{},"ISSN":["2090-6668","2090-6676"],"issn-type":[{"value":"2090-6668","type":"print"},{"value":"2090-6676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2632593"}}