M Ashwin Reddy1, Mussa Butt2, Anne-Marie Hinds2, Catriona Duncan3, Elizabeth A Price4, Mandeep S Sagoo5, Zerrin Onadim4. 1. Retinoblastoma Service, Royal London Hospital, London, United Kingdom; NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London, Institute of Ophthalmology, London, United Kingdom. Electronic address: ashwin.reddy4@nhs.net. 2. Retinoblastoma Service, Royal London Hospital, London, United Kingdom. 3. Retinoblastoma Service, Royal London Hospital, London, United Kingdom; Paediatric Oncology Department, Great Ormond Street Hospital, London, United Kingdom. 4. Retinoblastoma Genetic Screening Unit, Royal London Hospital, London, United Kingdom. 5. Retinoblastoma Service, Royal London Hospital, London, United Kingdom; NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London, Institute of Ophthalmology, London, United Kingdom.
Abstract
PURPOSE: To compare the number of tumors per eye for mosaic carriers of RB1 pathogenic variants with full germline variants and the conversion from unilateral to bilateral disease. DESIGN: Retrospective cohort study comparing patients with retinoblastoma and different genetic subtypes: high penetrance (HP), low penetrance (LP), and mosaicism. PARTICIPANTS: Data were analyzed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London, United Kingdom. All familial patients had a parent with a known pathogenic variant even if the parent did not manifest the disease. MAIN OUTCOME MEASURES: Number of tumors per eye in children who developed retinoblastoma in that eye. Other outcomes included total number of tumors per patient, age at diagnosis, laterality at presentation and later, sex, and stage according to International Intraocular Retinoblastoma Classification. RESULTS: A total of 111 patients were included: 64 full germline, familial patients (53 HP and 11 LP) and 47 mosaic patients. Twelve HP patients (23%) were unilateral, and 8 of 12 patients (67%) developed tumors in their previously unaffected eye. A total of 34 mosaic patients (72%) were unilateral, and only 2 (6%) developed tumors in their unaffected eye. Age at diagnosis was higher in mosaic patients (median, 22 months) than in HP patients (median 7) (P < 0.00002). The number of tumors per eye was fewer in patients with mosaic alleles (median, 1.0; range, 1-6) compared with patients with HP alleles (median, 3.0; range, 1-8) (P < 0.0003). All 3 children (4 eyes) with mosaicism and more than 2 tumors per eye had high levels of mosaicism. CONCLUSIONS: Children with mosaic alleles have fewer tumors per eye compared with those with known high-penetrant pathogenic variants and are more likely to remain unilateral. The level of mosaicism has an impact on laterality and number of tumors.
PURPOSE: To compare the number of tumors per eye for mosaic carriers of RB1 pathogenic variants with full germline variants and the conversion from unilateral to bilateral disease. DESIGN: Retrospective cohort study comparing patients with retinoblastoma and different genetic subtypes: high penetrance (HP), low penetrance (LP), and mosaicism. PARTICIPANTS: Data were analyzed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London, United Kingdom. All familial patients had a parent with a known pathogenic variant even if the parent did not manifest the disease. MAIN OUTCOME MEASURES: Number of tumors per eye in children who developed retinoblastoma in that eye. Other outcomes included total number of tumors per patient, age at diagnosis, laterality at presentation and later, sex, and stage according to International Intraocular Retinoblastoma Classification. RESULTS: A total of 111 patients were included: 64 full germline, familial patients (53 HP and 11 LP) and 47 mosaic patients. Twelve HP patients (23%) were unilateral, and 8 of 12 patients (67%) developed tumors in their previously unaffected eye. A total of 34 mosaic patients (72%) were unilateral, and only 2 (6%) developed tumors in their unaffected eye. Age at diagnosis was higher in mosaic patients (median, 22 months) than in HP patients (median 7) (P < 0.00002). The number of tumors per eye was fewer in patients with mosaic alleles (median, 1.0; range, 1-6) compared with patients with HP alleles (median, 3.0; range, 1-8) (P < 0.0003). All 3 children (4 eyes) with mosaicism and more than 2 tumors per eye had high levels of mosaicism. CONCLUSIONS:Children with mosaic alleles have fewer tumors per eye compared with those with known high-penetrant pathogenic variants and are more likely to remain unilateral. The level of mosaicism has an impact on laterality and number of tumors.
Authors: David H Abramson; Diana Mandelker; Jasmine H Francis; Ira J Dunkel; A Rose Brannon; Ryma Benayed; Michael F Berger; Maria E Arcila; Marc Ladanyi; Danielle Novetsky Friedman; Gowtham Jayakumaran; Monica S Diosdado; Melissa A Robbins; Dianna Haggag-Lindgren; Neerav Shukla; Michael Walsh; Prachi Kothari; Dana W Y Tsui Journal: Ophthalmol Sci Date: 2021-03-16