{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:15:11Z","timestamp":1783610111742,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201ccurrent research annual funding\u201d of the Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To describe the long-term, multimodal follow-up and multidisciplinary evaluation of two pediatric patients with CDH3-related retinopathy, discussing the genotypic and phenotypic spectrum of this rare cadherinopathy. Design: Retrospective observational case series. Methods: Two unrelated children with early-onset macular dystrophy and congenital hypotrichosis underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography (SD-OCT), blue-light fundus autofluorescence (BAF), microperimetry, and full-field electroretinography (ffERG), combined with dermatologic assessment and exome sequencing. Follow-up extended over 4 years in Patient 1 and 15 years in Patient 2. Results: Both patients showed sharply demarcated posterior pole chorioretinal atrophy with preservation of the peripheral retina and stable best-corrected visual acuity throughout follow-up. Microperimetry documented localized sensitivity loss with limited progression. SD-OCT revealed persistent ellipsoid zone disruption, retinal pigment epithelium atrophy, and outer retinal tubulations. Dermatologic evaluation confirmed congenital hypotrichosis without nail abnormalities; one patient exhibited mild fifth finger clinodactyly. Genetic testing identified the following two distinct homozygous CDH3 variants: a splice-site mutation (c.160+1G&gt;A) and a frameshift insertion (c.1837dup, p.(Asp613Glyfs*4)). Conclusions:CDH3 retinopathy presents with a characteristic multimodal imaging pattern of localized macular atrophy and slow functional decline associated with congenital hypotrichosis. A comprehensive multidisciplinary approach was essential for the correct diagnosis and a better and more thorough definition of the clinical presentation. Detailed long-term follow-up supports the hypothesis of retinal pigment epithelium dysfunction or maldevelopment rather than widespread retinal degeneration. Recognition of this phenotype is critical for accurate diagnosis, genetic counseling, and future gene-therapy strategies targeting the preserved peripheral retina.<\/jats:p>","DOI":"10.3390\/jcm15145393","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"5393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CDH3 Retinopathy: Long-Term Multimodal Follow-Up with Pediatric Multidisciplinary Insights"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-9379","authenticated-orcid":false,"given":"Elisa","family":"Marziali","sequence":"first","affiliation":[{"name":"Pediatric Ophthalmology, Meyer Children\u2019s Hospital IRCCS, Viale Pieraccini 24, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0188-0781","authenticated-orcid":false,"given":"Chiavetta","family":"Elia","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology, Meyer Children\u2019s Hospital IRCCS, Viale Pieraccini 24, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bargiacchi","sequence":"additional","affiliation":[{"name":"Medical Genetics Division, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6528-1841","authenticated-orcid":false,"given":"Giorgia","family":"Mancano","sequence":"additional","affiliation":[{"name":"Medical Genetics Division, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-1360","authenticated-orcid":false,"given":"Rosangela","family":"Artuso","sequence":"additional","affiliation":[{"name":"Medical Genetics Division, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-6464","authenticated-orcid":false,"given":"Elia","family":"Dirupo","sequence":"additional","affiliation":[{"name":"Medical Genetics Division, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-0172","authenticated-orcid":false,"given":"Lucia","family":"Tiberi","sequence":"additional","affiliation":[{"name":"Medical Genetics Division, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Daniotti","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Neuroscience Department, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pochiero","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Neuroscience Department, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Filippeschi","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, Department of Pediatrics, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Oranges","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, Department of Pediatrics, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, 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 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"}]},{"given":"Salvatore","family":"Angileri","sequence":"additional","affiliation":[{"name":"Research Collaborator Nurse, Operational Research Unit of Clinical and Cellular Physiopathology, Meyer Children\u2019s Hospital IRCCS, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pina","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology, Meyer Children\u2019s 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