Abstract
Genetic counseling for retinoblastoma is simple at first glance but complex in practice. The appearance of simplicity, in part, lies in the fact that there is only one gene, RB1, involved. The fact that almost all patients with bilateral retinoblastoma have a germline mutation in RB1 reinforces that perception. However, for those with unilateral retinoblastoma, genetic counseling is less straightforward as only about 15–20 % will have a germline mutation. Although most patients are young children whose parents have specific concerns, genetic counselors must also be prepared to counsel adult Rb survivors who are at risk for second non-ocular cancers. Mosaicism and low-penetrance mutations may make risk assessments difficult. The optimum surveillance strategy for second primary cancers in retinoblastoma survivors has not been developed so it is difficult to offer guidance to mutation carriers who want to manage their cancer risk. Finally, pregnant patients whose fetuses are at risk for retinoblastoma pose challenges for the geneticist since RB1 gene testing must be completed within a narrow time frame.
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References
Albrecht P, Ansperger-Rescher B, Schuler A, et al. Spectrum of gross deletions and insertions in the RB1 gene in patients with retinoblastoma and association with phenotypic expression. Hum Mutat. 2005;26(5):437–45.
Lohmann DR, Gallie BL. Retinoblastoma: revisiting the model prototype of inherited cancer. Am J Med Genet C Semin Med Genet. 2004;129(1):23–8.
Kallioniemi A, Kallioniemi OP, Waldman FM, et al. Detection of retinoblastoma gene copy number in metaphase chromosomes and interphase nuclei by fluorescence in situ hybridization. Cytogenet Cell Genet. 1992;60(3–4):190–3.
Dudin G, Nasr A, Traboulsi E, et al. Hereditary retinoblastoma and 13q–mosaicism. Cytogenet Cell Genet. 1984;38(3):235–7.
Greger V, Passarge E, Horsthemke B. Somatic mosaicism in a patient with bilateral retinoblastoma. Am J Hum Genet. 1990;46(6):1187–93.
Kivela T, Tuppurainen K, Riikonen P, Vapalahti M. Retinoblastoma associated with chromosomal 13q14 deletion mosaicism. Ophthalmology. 2003;110(10):1983–8.
Munier FL, Thonney F, Girardet A, et al. Evidence of somatic and germinal mosaicism in pseudo-low-penetrant hereditary retinoblastoma, by constitutional and single-sperm mutation analysis. Am J Hum Genet. 1998;63(6):1903–8.
Ribeiro MC, Andrade JA, Erwenne CM, Brunoni D. Bilateral retinoblastoma associated with 13q-mosaicism. Possible manifestation of a germinal mutation. Cancer Genet Cytogenet. 1988;32(2):169–75.
Sippel KC, Fraioli RE, Smith GD, et al. Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling. Am J Hum Genet. 1998;62(3):610–9.
Van Esch H, Aerssens P, Fryns JP. The importance of excluding 13q deletion mosaicism in the diagnosis of retinoblastoma associated with dysmorphic features. Genet Couns. 2005;16(1):91–3.
Dalamon V, Surace E, Giliberto F, et al. Detection of germline mutations in argentine retinoblastoma patients: low and full penetrance retinoblastoma caused by the same germline truncating mutation. J Biochem Mol Biol. 2004;37(2):246–53.
Huang Q, Dryja TP, Yandell DW. Distinct Rb gene point mutations in families showing low penetrance of hereditary retinoblastoma. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998;15(3):139–42.
Lohmann DR, Brandt B, Hopping W, et al. Distinct RB1 gene mutations with low penetrance in hereditary retinoblastoma. Hum Genet. 1994;94(4):349–54.
Taylor M, Dehainault C, Desjardins L, et al. Genotype-phenotype correlations in hereditary familial retinoblastoma. Hum Mutat. 2007;28(3):284–93.
Sanchez-Sanchez F, Ramirez-Castillejo C, Weekes DB, et al. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma. Hum Mutat. 2007;28(2):159–67.
Munier FL, Wang MX, Spence MA, et al. Pseudo low penetrance in retinoblastoma. Fortuitous familial aggregation of sporadic cases caused by independently derived mutations in two large pedigrees. Arch Ophthalmol. 1993;111(11):1507–11.
Brichard B, Heusterspreute M, De Potter P, et al. Unilateral retinoblastoma, lack of familial history and older age does not exclude germline RB1 gene mutation. Eur J Cancer. 2006;42(1):65–72.
Barbosa RH, Vargas FR, Lucena E, et al. Constitutive RB1 mutation in a child conceived by in vitro fertilization: implications for genetic counseling. BMC Med Genet. 2009;10:75.
National Retinoblastoma Strategy Canadian Guidelines for Care: Strategie therapeutique du retinoblastome guide clinique canadien. Can J Ophthalmol. 2009;44 Suppl 2:S1–88.
Squire J, Gallie BL, Phillips RA. A detailed analysis of chromosomal changes in heritable and non-heritable retinoblastoma. Hum Genet. 1985;70(4):291–301.
Grasemann C, Gratias S, Stephan H, et al. Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma. Oncogene. 2005;24(42):6441–9.
Gratias S, Schuler A, Hitpass LK, et al. Genomic gains on chromosome 1q in retinoblastoma: consequences on gene expression and association with clinical manifestation. Int J Cancer. 2005;116(4):555–63.
Marchong MN, Chen D, Corson TW, et al. Minimal 16q genomic loss implicates cadherin-11 in retinoblastoma. Mol Cancer Res. 2004;2(9):495–503.
Orlic M, Spencer CE, Wang L, Gallie BL. Expression analysis of 6p22 genomic gain in retinoblastoma. Genes Chromosomes Cancer. 2006;45(1):72–82.
Berger JC, Vander Griend DJ, Robinson VL, et al. Metastasis suppressor genes: from gene identification to protein function and regulation. Cancer Biol Ther. 2005;4(8):805–12.
Kauffman EC, Robinson VL, Stadler WM, et al. Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site. J Urol. 2003;169(3):1122–33.
Keller ET. Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP). Anticancer Drugs. 2004;15(7):663–9.
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Clark, R.D., Avishay, S.G. (2015). Retinoblastoma: Genetic Counseling and Testing. In: Singh, A., Murphree, A., Damato, B. (eds) Clinical Ophthalmic Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43451-2_8
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DOI: https://doi.org/10.1007/978-3-662-43451-2_8
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