Paper 37

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Mosaic Carriers of RB1 Develop Fewer Tumors Compared to Retinoblastoma Patients with Heterozygous Germline Mutations

 Ashwin Reddy, FRCOphth; Mussa Butt, BSc; Anne-Marie Hinds, FRCOphth; Catriona Duncan, MRCPCH; Tanzina Chowdhury, MRCPCH; Elizabeth A. Price, PhD; Mandeep S. Sagoo, FRCS (Ed); Zerrin Onadim, PhD
Royal London Hospital, Barts Health NHS Trust
London UK

Introduction:  The role of mosaicism in Retinoblastoma (Rb) is increasingly being recognised as molecular genetic tests become more sensitive (1). There is conflicting information regarding the phenotypic characteristics of mosaicism such as age of onset and laterality (2,3).

Methods:  A retrospective analysis of mosaic and heterozygous RB1 mutation carriers (low penetrant (LP) and high penetrant (HP)) from 1992 to 2017 was conducted.  Tumor number per eye was assessed in patients classified with A, B and C tumors using the International Intraocular Retinoblastoma Classification system. Patients with D or E group eyes were assessed based upon age at diagnosis.

Results:  Data were analysed for 107 patients : 64 were full germline familial patients (53 HP and 11 LP) and 43 mosaic germline patients.  25% HP patients were unilateral and 9 of 13 developed tumors in their previously unaffected eye.  72% of mosaic patients were unilateral and only 1 of 31 developed tumours in their unaffected eye. Age at diagnosis was higher in mosaic patients (median 16 months range 2-117) than HP patients (median 7 range 2-33) (p<0.001). Tumor number per eye was lower in mosaic patients (median 1.5 tumors range 1-6) than HP patients (median 3 range 1-8) (p=0.009).

Discussion:  Patients with mosaicism develop less tumors compared to patients with HP mutations in eyes with Rb at presentation. Advanced disease presents at an older age.

Conclusion:  This is the first study to demonstrate that Rb mosaicism is associated with fewer tumors in eyes with Rb. This provides important prognostic information for clinicians and families.

1. Price EA, Price K, Kolkiewicz K, et al. Spectrum of RB1 mutations identified in 403 retinoblastoma patients. J Med Genet. 2014;51:208-14
2. Kivelä T, Tuppurainen K, Riikonen P, Vapalahti M. Retinoblastoma associated with chromosomal 13q14 deletion mosaicism. Ophthalmology. 2003;110:1983-8
3. Astudillo PP, Chan HS, Héon E, Gallie BL. Late-diagnosis retinoblastoma with germline mosaicism in an 8-year-old. J AAPOS. 2014 ;18:500-2

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