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This study aims to characterize their long-term clinical and radiological evolution and identify factors influencing disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective observational study of patients with anoctaminopathies in the Valencian Community (Spain). Demographic, clinical, genetic, ancillary tests, and serial muscle MRI data were analyzed using univariate and Bayesian multivariate models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty patients (21 males) from 23 families were included. Median disease duration was 13.5\u00a0years, and follow-up was 7\u00a0years (range 3\u201331). Median age at first assessment was 43.5\u00a0years (range 9\u201378). Most patients presented with pseudometabolic myopathy (47%) or asymptomatic hyperCKemia (37%), while 16% had LGMD-R12\/MMD3. Nearly one-third of symptomatic patients had a documented asymptomatic hyperCKemia period (median 5.5\u00a0years). At last assessment, 27% had LGMD-R12\/MMD3, 43% had pseudometabolic myopathy, and 30% remained asymptomatic. The most frequent variants were c.191dupA (35%) and c.692G\u2009&gt;\u2009T (22%). CK levels, biopsy and EMG findings did not distinguish phenotypes. Baseline MRI revealed fat infiltration and STIR hyperintensities in most patients across all phenotypes. Muscle involvement progressed in 95% of serial scans. STIR hyperintensities preceded fat replacement in approximately 50% of muscles. More severe phenotypes correlated with older age, loss-of-function variants, and higher MRI T1 scores. Estimated prevalence was 1.8\/100,000 in our region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ANO5<\/jats:italic>\n                      -related myopathies show progressive muscle involvement regardless of phenotype. Muscle MRI analysis provides valuable outcome measures for monitoring and future clinical trials, with STIR hyperintensities as a sensitive biomarker of disease activity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13805-1","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T01:59:18Z","timestamp":1776218358000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term clinical and radiological trajectories in ANO5-related myopathies highlight muscle MRI as a predictor of disease progression"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6447-6388","authenticated-orcid":false,"given":"Karolina","family":"Aragon-Gawinska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-9314","authenticated-orcid":false,"given":"Pilar","family":"Mart\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6169-3844","authenticated-orcid":false,"given":"Inmaculada","family":"Azor\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-1180","authenticated-orcid":false,"given":"Rafael","family":"Sivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-5250","authenticated-orcid":false,"given":"Elena","family":"Aller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-7374","authenticated-orcid":false,"given":"Inmaculada","family":"Pitarch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Benlloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"T\u00e1rrega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Vilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmina","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"S\u00e1nchez-Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"M\u00e1s-Estell\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Frasquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-7938","authenticated-orcid":false,"given":"Juan F.","family":"V\u00e1zquez-Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Otero-Borell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Vilchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0532-2872","authenticated-orcid":false,"given":"Juan J.","family":"Vilchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4716-2667","authenticated-orcid":false,"given":"Teresa","family":"Sevilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2349-7481","authenticated-orcid":false,"given":"Nuria","family":"Muelas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"13805_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.013","author":"V Bolduc","year":"2010","unstructured":"Bolduc V, Marlow G, Boycott KM et al (2010) Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. 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