JOURNAL ARTICLE

Prognostic information for known genetic carriers of RB1 pathogenic variants (germline and mosaic)

M Ashwin Reddy, Mussa Butt, Anne-Marie Hinds, Catriona Duncan, Elizabeth A Price, Mandeep S Sagoo, Zerrin Onadim
Ophthalmology Retina 2020 August 21
32835838

OBJECTIVE: 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 (HP: high penetrant, LP: low penetrant & mosaicism).

SUBJECTS: Data were analysed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London UK. 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: 111 patients were included: 64 full germline, familial patients (53 HP and 11 LP) & 47 were mosaic patients. 12 (23%) of HP patients were unilateral and 8 of 12 (67%) developed tumors in their previously unaffected eye. 34 (72%) of mosaic patients were unilateral and only 2 (6%) developed tumors in their unaffected eye. Age at diagnosis was higher in mosaic patients (median 22 months) than HP patients (median 7) (p<0.00002). Number of tumors per eye was fewer in patients with mosaic alleles (median 1.0 range 1-6) compared to patients with HP alleles (median 3.0 range 1-8) (p<0.0003). All three 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 to 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.

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