{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:00:32Z","timestamp":1791518432788,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Usher syndrome (USH), the most common cause of combined deaf-blindness, is a genetically and phenotypically heterogeneous disorder characterized by congenital hearing impairment and progressive vision loss due to rod-cone dystrophy. Although the original classification in three subtypes (USH I, USH II, and USH III) is still valid, recent findings have changed and widened perspectives in its classification, genotype\u2013phenotype correlations, and management strategies: Objective: This study aims to provide new insights into the classification of Usher syndrome, explore the genotype-phenotype correlations, and review current and emerging management strategies. Methods: A comprehensive literature review has been conducted, incorporating data from clinical studies, genetic databases, and patient registries. Results: Recent studies have led to the identification of several novel pathogenic variants in the USH genes, leading to refined subclassifications of Usher syndrome. Interactions between different genes being part of the network of this ciliopathy have been investigated and new mechanisms unveiled. Significant correlations were found between certain genotypes and the presentation of both auditory and visual phenotypes. For instance, pathogenic variants in the MYO7A gene (USH1B) were generally associated with more severe hearing impairment and earlier onset of retinal dystrophy, if compared to other USH genes-related forms. Other genes, such as USH1G, traditionally considered as causing a specific subtype, can display phenotypic heterogeneity in some patients. Conclusions: This review provides insights into a better understanding of Usher syndrome that considers recent findings regarding its genetic causes and clinical features. Precise genotype\u2013phenotype correlations can lead to better genetic counselling, more precise characterization of the natural history of the condition, and a personalized and effective management approach. Recent progress has been made in research into gene-specific therapies that appear promising for improving the quality of life for individuals affected by Usher syndrome.<\/jats:p>","DOI":"10.3390\/genes16030332","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:31:42Z","timestamp":1741764702000},"page":"332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Usher Syndrome: New Insights into Classification, Genotype\u2013Phenotype Correlation, and Management"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"first","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, 153-173 Marylebone Rd., London NW1 5QH, UK"},{"name":"Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Via Pansini 5, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Eye Clinic Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, Via Sant\u2019Eupio, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-0185","authenticated-orcid":false,"given":"Antonino","family":"Maniaci","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Eye Clinic Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-0786","authenticated-orcid":false,"given":"Rosa","family":"Giglio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, Via Farneto 3, 34100 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-6729","authenticated-orcid":false,"given":"Michele","family":"Reibaldi","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, University of Turin, Corso Bramante 88, 10126 Turin, Italy"},{"name":"Department of Ophthalmology, \u201cCity of Health and Science\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, 153-173 Marylebone Rd., London NW1 5QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, Via Farneto 3, 34100 Trieste, Italy"},{"name":"Department of Ophthalmology, University Hospital of Udine, p.le S. 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