{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:06:59Z","timestamp":1791594419442,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Brittle cornea syndrome (BCS) is a rare, autosomal recessive connective tissue disorder characterized by extreme corneal thinning, high myopia, and increased risk of spontaneous or trauma-induced ocular rupture. It is primarily caused by mutations in the ZNF469 or PRDM5 genes, which regulate extracellular matrix integrity. Early recognition and diagnosis of BCS are crucial to prevent severe visual impairment. This report presents two genetically confirmed cases of BCS in Albanian siblings, emphasizing the diagnostic value of whole-exome sequencing and individualized surgical management strategies. Case Presentation: Two siblings\u2014a 28-year-old male and a 25-year-old female\u2014presented with progressive visual deterioration and marked corneal thinning (&lt;200 \u00b5m). Both had a history of spontaneous ocular rupture following minor trauma in the contralateral eye. Detailed ophthalmologic evaluation revealed keratoglobus, high myopia, and irregular astigmatism. Genetic testing identified the homozygous pathogenic variant c.974delG (p.Cys325LeufsX2) in the PRDM5 gene in both cases. The male underwent penetrating keratoplasty (PKP), achieving a best-corrected visual acuity (BCVA) of 20\/30. The female initially underwent deep anterior lamellar keratoplasty (DALK), which was converted to PKP intraoperatively due to central endothelial perforation, resulting in a BCVA of 20\/25. Both patients remained complication-free over a 7-year follow-up period. Conclusions: These cases highlight the importance of early genetic diagnosis and a tailored surgical approach in managing BCS. Long-term monitoring and protective strategies are essential to prevent complications. Incorporating genetic testing into clinical practice can enhance diagnostic accuracy and guide personalized treatment plans in patients with hereditary corneal dystrophies.<\/jats:p>","DOI":"10.3390\/diagnostics15131596","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T06:49:38Z","timestamp":1750747778000},"page":"1596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Brittle Cornea Syndrome: Molecular Diagnosis and Management"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-6036","authenticated-orcid":false,"given":"Mattia","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Di Venere Hospital, 70012 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"U.O.C Ophthalmology, \u201cDi Venere\u201d Hospital, 70012 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Scollo","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\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, 153-173 Marylebone Rd, London NW15QH, UK"},{"name":"Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Via Pansini 5, 80131 Napoli, Italy"},{"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\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, 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":"Department of Ophthalmology, University of Catania, 95123 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, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Lapenna","sequence":"additional","affiliation":[{"name":"U.O.C Ophthalmology, \u201cDi Venere\u201d Hospital, 70012 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101124","DOI":"10.1016\/j.bonr.2021.101124","article-title":"Does brittle cornea syndrome have a bone fragility phenotype?","volume":"15","author":"Cundy","year":"2021","journal-title":"Bone Rep."},{"key":"ref_2","first-page":"4381273","article-title":"Case Series of Brittle Cornea Syndrome","volume":"2020","author":"Eleiwa","year":"2020","journal-title":"Case Rep. Ophthalmol. 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