The mutational landscape of hereditary retinoblastoma and genotype-phenotype associations in Lebanon.
Bilaterality strongly associated with hereditary retinoblastoma versus sporadic disease.
The mutational landscape of hereditary retinoblastoma and genotype-phenotype associations in Lebanon.
Retinoblastoma is the most common intraocular tumor of childhood.
This study aimed to characterize the spectrum of RB1 variants in hereditary retinoblastoma and explore genotype-phenotype associations in a Lebanese cohort.
A retrospective chart review was conducted on retinoblastoma patients enrolled in the Children's Cancer Institute at the American University of Beirut Medical Center from 2012 to 2022.
hereditary cases showed tumors in both eyes far more often than sporadic cases
A total of 47 patients underwent genetic testing; 63% had hereditary retinoblastoma with 23 patients carrying single nucleotide changes, including four novel mutations, 3 patients with submicroscopic deletions/duplications, and 3 with deletion 13q syndrome.
Nonsense mutations were most frequent (52.2%), followed by frameshift and splice-site alterations.
Median age at diagnosis was younger in the hereditary group, although not statistically significant.
Among the 3 patients with deletion 13q, two exhibited severe psychomotor and developmental delays.
Hereditary retinoblastoma accounted for 63% of cases, with 23 pathogenic variants including four novel ones. Bilaterality and Syrian nationality were significantly associated with RB1 positivity.
This study underscores the importance of comprehensive RB1 genetic testing in improving diagnostic accuracy, guiding treatment decisions, and supporting genetic counselling, particularly in non-Western populations.