{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:21:48Z","timestamp":1779175308884,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["339437"],"award-info":[{"award-number":["339437"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["23281"],"award-info":[{"award-number":["23281"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015736","name":"Folkh\u00e4lsanin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010116","name":"Medicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004810","name":"Samfundet Folkh\u00e4lsan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002342","name":"Suomalainen Tiedeakatemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005633","name":"Syd\u00e4ntutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Tibial muscular dystrophy (TMD) is a dominant late onset distal titinopathy. It was first described in Finnish patients 3 decades ago. TMD patients with several other <jats:italic>TTN<\/jats:italic> mutations occur in many European populations. In this retrospective study, we were able to obtain longitudinal follow\u2010up data of the disease progression over 15\u2009years in 137 TMD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrieved clinical data retrospectively from three examinations spanning a period of 15\u2009years. The data were analyzed in R. Frequencies, percentages, and median values were used to describe data. Probability values were determined with the chi\u2010squared test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the cohort, the first symptoms were walking difficulties (97.8%) and weakness in distal lower limbs (98.5%). The progression of the weakness in distal lower limbs was moderate, and in the proximal lower limbs and proximal upper limbs it was mild. The distal upper limbs were not affected. Magnetic resonance imaging results indicated fatty degeneration preferentially in lower leg anterior muscles, gluteus minimus, and hamstring muscles. Serum creatine kinase values in the cohort were mostly normal (40.7%) or mildly elevated (53.7%). The data suggest that 50% of patients need walking aids by the age of 88\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite individual variability of severity, the overall disability due to walking difficulties and upper limb weakness remained moderate even at very advanced ages, and cardiomyopathy did not develop due to the titin defect alone. The acquired results promote the correct identification of TMD, and the obtained trajectories of disease evolution can be used as natural history data for any therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15688","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:25:11Z","timestamp":1674566711000},"page":"1080-1088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long\u2010term favorable prognosis in late onset dominant distal titinopathy: Tibial muscular dystrophy"],"prefix":"10.1111","volume":"30","author":[{"given":"Victoria","family":"Lillback","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Medicum University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-244X","authenticated-orcid":false,"given":"Marco","family":"Savarese","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Medicum University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niina","family":"Sandholm","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hackman","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Medicum University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarne","family":"Udd","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Research Center  Helsinki Finland"},{"name":"Tampere Neuromuscular Center Tampere University Hospital  Tampere Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/342380"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880141103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1993.00540060044015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5372-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10647"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4899"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190423"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24102"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.07.010"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136873"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1264"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.07.011"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.199"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.657949"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.774"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt-2020-0066"},{"key":"e_1_2_11_18_1","volume-title":"GeneReviews\u00ae [Internet]","author":"Udd B","year":"1993"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt494"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25241"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51434"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.09.032"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-160158"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0914-2"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3719"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.190"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15688","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15688","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T13:26:53Z","timestamp":1692710813000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/ene.15688"],"URL":"https:\/\/doi.org\/10.1111\/ene.15688","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,8]]},"assertion":[{"value":"2022-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}