{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:07:38Z","timestamp":1792670858163,"version":"4.5.0"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010093","name":"King Khaled Eye Specialist Hospital","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100010093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Retinoblastoma is a rare but malignant pediatric retinal tumor, affecting 1 in 15,000\u201320,000 live births annually. It arises from biallelic mutations in the RB1 tumor suppressor gene (chromosome 13q14.2), leading to uncontrolled cell cycle progression. Clinically, it presents as unilateral (60%) or bilateral (40%) disease, with leukocoria and strabismus as hallmark signs. Untreated, retinoblastoma is fatal due to metastatic spread. The disease follows Knudson\u2019s two-hit model: heritable forms (30\u201340% of cases) involve a germline RB1 mutation (M1) and a somatic second hit (M2), predisposing to bilateral\/multifocal tumors and secondary cancers. Non-heritable cases (60\u201370%) result from somatic RB1 mutations or, rarely, MYCN amplification (2%). Genetic testing is critical to classify risk (H0, H1, and HX categories), guide surveillance, and inform family counseling. Bilateral cases almost always harbor germline mutations, while 15% of unilateral cases may carry germline\/mosaic RB1 defects. Advanced techniques (Sanger\/NGS sequencing for mutation detection, NGS for copy number alterations, and methylation assays) detect RB1 mutations, CNVs, and epigenetic silencing. Tumor DNA analysis resolves ambiguous cases. H1 patients require intensive ocular and brain MRI surveillance, while H0 cases need no follow-up. Prenatal\/preimplantation genetic diagnosis (PGD) can prevent transmission in high-risk families. Emerging research explores additional genes (BCOR, CREBBP) and MYCN-amplified subtypes. Genetic counseling addresses recurrence risks, reproductive options, and long-term cancer monitoring. Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies.<\/jats:p>","DOI":"10.3390\/genes16091031","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T16:18:15Z","timestamp":1756484295000},"page":"1031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetics of Retinoblastoma: An Overview and Significance of Genetic Testing in Clinical Practice"],"prefix":"10.3390","volume":"16","author":[{"given":"Khaled K.","family":"Abu-Amero","sequence":"first","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A.","family":"Kondkar","sequence":"additional","affiliation":[{"name":"Glaucoma Research Chair, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3607-395X","authenticated-orcid":false,"given":"Naif A. M.","family":"Almontashiri","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"},{"name":"College of Applied Medical Sciences and Center for Genetics and Inherited Diseases, Taibah University, Madinah 41477, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1125-7891","authenticated-orcid":false,"given":"Abdullah M.","family":"Khan","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology and Strabismus Division and Ocular Oncology Division, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza M. Y.","family":"Maktabi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Ocular Oncology Division, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2746-0784","authenticated-orcid":false,"given":"Syed","family":"Hameed","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"AlMesfer","sequence":"additional","affiliation":[{"name":"Pediatric Ophthalmology and Strabismus Division and Ocular Oncology Division, King Khaled Eye Specialist Hospital and Research Center, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1136\/bjo.2008.138750","article-title":"Incidence of Retinoblastoma in the USA: 1975\u20132004","volume":"93","author":"Broaddus","year":"2009","journal-title":"Br. 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