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Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and\/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype\u2013phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals.<\/jats:p>","DOI":"10.3390\/genes16070745","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T05:29:58Z","timestamp":1751002198000},"page":"745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phenotypic and Genotypic Characterization of 171 Patients with Syndromic Inherited Retinal Diseases Highlights the Importance of Genetic Testing for Accurate Clinical Diagnosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Sofia","family":"Kulyamzin","sequence":"first","affiliation":[{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Leibu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ehrenberg","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-1873","authenticated-orcid":false,"given":"Nitza","family":"Goldenberg-Cohen","sequence":"additional","affiliation":[{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Department of Ophthalmology, Bnai Zion Medical Center, Haifa 3339419, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Zayit-Soudry","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Ophthalmology, Rabin Medical Center, Petach Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-7538","authenticated-orcid":false,"given":"Eedy","family":"Mezer","sequence":"additional","affiliation":[{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Department of Ophthalmology, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ygal","family":"Rotenstreich","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer 5262100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-6774","authenticated-orcid":false,"given":"Iris","family":"Deitch","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rabin Medical Center, Petach Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan M.","family":"Panneman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-444X","authenticated-orcid":false,"given":"Dinah","family":"Zur","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel"},{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Chervinsky","sequence":"additional","affiliation":[{"name":"Genetics Institute, Emek Medical Center, Afula 1834111, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavit A.","family":"Shalev","sequence":"additional","affiliation":[{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"},{"name":"Genetics Institute, Emek Medical Center, Afula 1834111, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans P. M.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-5811","authenticated-orcid":false,"given":"Dror","family":"Sharon","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9038-0067","authenticated-orcid":false,"given":"Susanne","family":"Roosing","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Ben-Yosef","sequence":"additional","affiliation":[{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ben-Yosef, T. 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