{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:13:33Z","timestamp":1776312813180,"version":"3.50.1"},"reference-count":40,"publisher":"BMJ","funder":[{"name":"Italian Ministry of Health","award":["Annual funding by Italian Ministry of Health (RRC)"],"award-info":[{"award-number":["Annual funding by Italian Ministry of Health (RRC)"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Natural history of spinal muscular atrophy (SMA) in adult age has not been fully elucidated yet, including factors predicting disease progression and response to treatments. Aim of this retrospective, cross-sectional study, is to investigate motor function across different ages, disease patterns and gender in adult SMA untreated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inclusion criteria were as follows: (1) clinical and molecular diagnosis of SMA2, SMA3 or SMA4 and (2) clinical assessments performed in adult age (&gt;18 years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 64 (38.8%) females and 101 (61.2%) males (p=0.0025), among which 21 (12.7%) SMA2, 141 (85.5%) SMA3 and 3 (1.8%) SMA4. Ratio of sitters\/walkers within the SMA3 subgroup was significantly (p=0.016) higher in males (46\/38) than in females (19\/38). Median age at onset was significantly (p=0.0071) earlier in females (3 years; range 0\u201316) than in males (4 years; range 0.3\u201328), especially in patients carrying 4<jats:italic>SMN2<\/jats:italic>copies. Median Hammersmith Functional Rating Scale Expanded scores were significantly (p=0.0040) lower in males (16, range 0\u201364) than in females (40, range 0\u201362); median revised upper limb module scores were not significantly (p=0.059) different between males (24, 0-38) and females (33, range 0\u201338), although a trend towards worse performance in males was observed. In SMA3 patients carrying three or four SMN2 copies, an effect of female sex in prolonging ambulation was statistically significant (p=0.034).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data showed a relevant gender effect on SMA motor function with higher disease severity in males especially in the young adult age and in SMA3 patients.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2022-329320","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T17:25:14Z","timestamp":1665509114000},"page":"jnnp-2022-329320","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Adults with spinal muscular atrophy: a large-scale natural history study shows gender effect on disease"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0932-5173","authenticated-orcid":false,"given":"Lorenzo","family":"Maggi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-6525","authenticated-orcid":false,"given":"Luca","family":"Bello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Bonanno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Govoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Caponnetto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigia","family":"Passamano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Grandis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Trojsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Cerri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Gardani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfredi","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-8222","authenticated-orcid":false,"given":"Giulio","family":"Gadaleta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittoria","family":"Zangaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Caumo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariantonietta","family":"Maioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaella","family":"Tanel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Saccani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megi","family":"Meneri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-2394","authenticated-orcid":false,"given":"Veria","family":"Vacchiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eustachio","family":"D'Errico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Bortolani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Pavesi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Zanin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5425-969X","authenticated-orcid":false,"given":"Stefania","family":"Corti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Silvestrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Politano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Schenone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2546-4357","authenticated-orcid":false,"given":"Stefano Carlo","family":"Previtali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Berardinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Turri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Verriello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Coccia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9810-5737","authenticated-orcid":false,"given":"Renato","family":"Mantegazza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco","family":"Liguori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2852-7512","authenticated-orcid":false,"given":"Massimiliano","family":"Filosto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianni","family":"Marrosu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Danilo","family":"Tiziano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella Laura","family":"Simone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Mongini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Comi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-4156","authenticated-orcid":false,"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"2022101910251889000_jnnp-2022-329320v2.1","doi-asserted-by":"crossref","DOI":"10.1007\/s10072-021-05258-3","article-title":"Spinal muscular atrophy: state of the art and new therapeutic strategies","author":"Messina","year":"2021","journal-title":"Neurol Sci"},{"key":"2022101910251889000_jnnp-2022-329320v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.11.005"},{"key":"2022101910251889000_jnnp-2022-329320v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.01.003"},{"key":"2022101910251889000_jnnp-2022-329320v2.4","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318271f7e4"},{"key":"2022101910251889000_jnnp-2022-329320v2.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.10.006"},{"key":"2022101910251889000_jnnp-2022-329320v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2012.05.067"},{"key":"2022101910251889000_jnnp-2022-329320v2.7","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008166"},{"key":"2022101910251889000_jnnp-2022-329320v2.8","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010540"},{"key":"2022101910251889000_jnnp-2022-329320v2.9"},{"key":"2022101910251889000_jnnp-2022-329320v2.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710504"},{"key":"2022101910251889000_jnnp-2022-329320v2.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30037-5"},{"key":"2022101910251889000_jnnp-2022-329320v2.12","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-323822"},{"key":"2022101910251889000_jnnp-2022-329320v2.13","doi-asserted-by":"publisher","DOI":"10.1177\/0883073811420294"},{"key":"2022101910251889000_jnnp-2022-329320v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.02.014"},{"key":"2022101910251889000_jnnp-2022-329320v2.15","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d3e308"},{"key":"2022101910251889000_jnnp-2022-329320v2.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0912-y"},{"key":"2022101910251889000_jnnp-2022-329320v2.17","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0156-7"},{"key":"2022101910251889000_jnnp-2022-329320v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.41"},{"key":"2022101910251889000_jnnp-2022-329320v2.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155085"},{"key":"2022101910251889000_jnnp-2022-329320v2.20","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13534"},{"key":"2022101910251889000_jnnp-2022-329320v2.21","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25900"},{"key":"2022101910251889000_jnnp-2022-329320v2.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)00284-5"},{"key":"2022101910251889000_jnnp-2022-329320v2.23","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0598-1"},{"key":"2022101910251889000_jnnp-2022-329320v2.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2017.06.002"},{"key":"2022101910251889000_jnnp-2022-329320v2.25","doi-asserted-by":"publisher","DOI":"10.3233\/JND-200563"},{"key":"2022101910251889000_jnnp-2022-329320v2.26","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.21.6.447"},{"key":"2022101910251889000_jnnp-2022-329320v2.27","first-page":"805","article-title":"Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy","volume":"57","author":"Cobben","year":"1995","journal-title":"Am J Hum Genet"},{"key":"2022101910251889000_jnnp-2022-329320v2.28","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(96)00350-1"},{"key":"2022101910251889000_jnnp-2022-329320v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91507-9"},{"key":"2022101910251889000_jnnp-2022-329320v2.30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.3.359"},{"key":"2022101910251889000_jnnp-2022-329320v2.31","doi-asserted-by":"publisher","DOI":"10.1086\/302369"},{"key":"2022101910251889000_jnnp-2022-329320v2.32","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01771-y"},{"key":"2022101910251889000_jnnp-2022-329320v2.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213680"},{"key":"2022101910251889000_jnnp-2022-329320v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.02.011"},{"key":"2022101910251889000_jnnp-2022-329320v2.35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.372318"},{"key":"2022101910251889000_jnnp-2022-329320v2.36","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.87908","article-title":"Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy","volume":"1","author":"Powis","year":"2016","journal-title":"JCI Insight"},{"key":"2022101910251889000_jnnp-2022-329320v2.37","doi-asserted-by":"publisher","DOI":"10.18388\/abp.2009_2521"},{"key":"2022101910251889000_jnnp-2022-329320v2.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102750"},{"key":"2022101910251889000_jnnp-2022-329320v2.39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131989"},{"key":"2022101910251889000_jnnp-2022-329320v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.03.036"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2022-329320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:26:08Z","timestamp":1666200368000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2022-329320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":40,"alternative-id":["10.1136\/jnnp-2022-329320"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2022-329320","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}