The Heredity of Retinoblastoma

Schappert-Kimmijser, J.; Hemmes, G.D.; Nijland, Reindert

doi:10.1159/000304891

Cited by 98 publications

(19 citation statements)

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“…It is possible that some of the cases originally ascertained as unilateral in this study later developed tumours in the other eye. Among 550 cases ascertained in the Netherlands, 31% were found to be bilateral (Schappert-Kimmijser et al, 1966), and in a study of 899 cases of retinoblastoma in France, 34% were bilateral (Bonaiti-Pellie, 1976). …”

Section: Discussionmentioning

confidence: 97%

“…Vogel bases his estimate, which is the one nearly always quoted for genetic counselling, on the joint results from seven separate studies, the largest study (Schappert-Kimmijser et al, 1966), giving a particularly high rate of affected children in the families of survivors from unilateral sporadic retinoblastoma. If the selection of cases included in some of these seven studies was biased this could lead to an overestimate of the risk: such bias could arise for instance if unilateral sporadic probands were included in a series after being ascertained through an affected offspring.…”

Section: Risks To Offspringmentioning

confidence: 99%

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Patterns of risk of hereditary retinoblastoma and applications to genetic counselling

Draper

Sanders²,

Brownbill³

et al. 1992

Br J Cancer

148

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A registry including information about nearly 1,600 cases of retinoblastoma diagnosed in Britain has been created at the Childhood Cancer Research Group. Cases have been classified as 'old germ cell mutation', 'new germ cell mutation' or 'sporadic non-hereditary'. For a population-based group of 918 cases diagnosed between 1962 and 1985 we have calculated the proportions of unilateral/bilateral and hereditary/non-hereditary cases. Bilateral cases represent 40% of the total number over this period; the proportion known to be hereditary is 44%, a higher proportion than has been reported elsewhere. By following up selected groups of cases, an estimate has been made of the proportions of siblings of retinoblastoma patients and offspring of survivors from retinoblastoma who are themselves affected with the disease. Where there is no previous family history, the risk for siblings of retinoblastoma patients of developing the disease is approximately 2% if the disease in the affected child is bilateral and 1% if it is unilateral, assuming that there are no other siblings; if there are unaffected siblings the risks for subsequent children are lower. Children of patients with hereditary retinoblastoma have a one in two chance of carrying the germ cell mutation and for those who are carriers the probability of developing retinoblastoma is very close to the accepted figure of 90% if the parents have bilateral retinoblastoma but probably less if they have the unilateral form. For children of patients not known to be carriers, the probability of developing retinoblastoma is estimated to be about 1%, considerably lower than the previously accepted figure of about 5%. Retinoblastoma kindreds consist mainly of bilateral cases but there is evidence that some kindreds have a high proportion of unilateral cases. The ways in which these findings may be used in conjunction with modern techniques of molecular biology for prenatal and postnatal genetic counselling are discussed.

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Section: Discussionmentioning

confidence: 97%

Section: Risks To Offspringmentioning

confidence: 99%

Patterns of risk of hereditary retinoblastoma and applications to genetic counselling

Draper

Sanders²,

Brownbill³

et al. 1992

Br J Cancer

148

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“…The national retinoblastoma register of the Netherlands (Schappert- Kimmijser et al 1966;DerKinderen 1987) was used. For our study, the register has recently been updated and the data verified (Moll et al 1995).…”

Section: Methodsmentioning

confidence: 99%

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862-1994

et al. 1996

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We wished to determine the influence of parental age at the birth of a retinoblastoma patient on the risk of sporadic hereditary retinoblastoma. The parental age at birth of 941 patients of the Dutch retinoblastoma register was identified and compared between sporadic hereditary and nonhereditary patients. In a subcohort , a comparison was made with parental age at birth in the general population, as obtained from the Central Bureau of Statistics. Missing birth dates of the parents of retinoblastoma patients were traced with the help of the municipal registries and the Central Bureau of Genealogy. The mean paternal age was 10.7 months higher and the mean maternal age was 11.0 months higher in the sporadic hereditary retinoblastoma patients than in parents of nonhereditary patients. In the subcohort, the mean paternal and maternal ages of sporadic hereditary patients were also higher (12.4 and 11.5 months, respectively) than those of the general population. All differences were statistically significant. This study shows that a high parental age is associated with an enhanced risk of sporadic hereditary retinoblastoma. IntroductionRetinoblastoma is a malignant pediatric tumor affecting the retina and occurring about once in 20 000 live births. Retinoblastoma occurs in a hereditary form (30%-40% of the patients) and a nonhereditary form (60%-70%; Vogel 1979). It develops following at least two (Knudson 1971; DerKinderen 1987) mutational events, namely, inactivation of both alleles of the retinoblastoma (RB1) gene at 13q14 (Cavenee et al. 1983;Dryja et al. 1986).The hereditary form results from a germline mutation which is present in all body cells. Among hereditary cases, a familial hereditary form and a sporadic hereditary form may be distinguished. An indication for the familial hereditary form is a parent with retinoblastoma or a family member with this disease, indicating that one of the parents must be a carrier of the RB1 gene. In the sporadic hereditary form, no other family members are affected, and the patient is the first person in the family with retinoblastoma. In the nonhereditary form, the retinoblastoma mutation is exclusively found in the tumor cells of the retina (Knudson 1971;Vogel 1979).Epidemiological observations suggest that parental age is related to the genesis of sporadic hereditary disorders such as Down's syndrome and achondroplasia. This is understandable, since the number of new mutations in germline cells increases with age (Penrose 1955;Vogel and Rathenberg 1975;Vogel 1979). The existence of an association of sporadic hereditary retinoblastoma with parental age is still controversial (Falls and Neel 1951;Stevenson and Martin 1957;Smith and Sorsby 1958;Macklin 1960;Matsunaga 1965;Fraser and Friedmann 1967;Tünte 1972;Pellié et al. 1973;Bunin et al. 1989;Matsunaga et al. 1990; DerKinderen et al. 1990). Furthermore, DNA investigations on some patients suggest that new germline mutations are principally of paternal orgin (Ejima et al. 1988;Dryja et al. 1989;Zhu et al. 1989). Th...

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“…This form of the disease generally affects both eyes, whereas the spontaneous form usually affects a single eye. The occurrence of retinoblastoma as both heritable and sporadic forms has allowed detailed statistical analyses, which indicate a relationship between these two forms of the disease (2)(3)(4)(5). A locus, RBJ, which plays a role in the development of this tumor, has been localized to the q14 band of human chromosome 13 through segregation analysis (6) and by the identification of specific deletions of this chromosomal region in some retinoblastoma patients or their tumors (7)(8)(9).…”

mentioning

confidence: 99%

Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.

Hansen¹,

Koufos²,

Gallie³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

370

134

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Survivors of the heritable form of retinoblastoma subsequently develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma. Here we present molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RBI locus. Similar events occur during the genesis of nonheritable osteosarcoma but not in several other embryonal tumors or sarcomas. These findings suggest that a conceptual approach toward defining the number of genes whose recessive mutant forms predispose to cancer is the molecular genetic analysis of clinically associated tumor types. They also suggest that the molecular basis of mixed cancer families may be the differential expression of a single pleiotropic recessive mutation by tissue specific mitotic segregation abnormalities.Retinoblastoma is one of a group of childhood tumors to which predisposition can be inherited as an autosomal dominant trait (1). This form of the disease generally affects both eyes, whereas the spontaneous form usually affects a single eye. The occurrence of retinoblastoma as both heritable and sporadic forms has allowed detailed statistical analyses, which indicate a relationship between these two forms of the disease (2-5). A locus, RBJ, which plays a role in the development of this tumor, has been localized to the q14 band of human chromosome 13 through segregation analysis (6) and by the identification of specific deletions of this chromosomal region in some retinoblastoma patients or their tumors (7)(8)(9).A model to unify these observations has been proposed (10), based on the previous hypothesis that as few as two mutations are required for malignant transformation (2-4). In this model, bilateral retinoblastoma cases have inherited a germinal mutation of the RBJ locus, which predisposes each cell to transformation by a further event. Evidence has recently been presented that suggests that these predisposing mutations are recessive at the cellular level, are expressed upon loss of the homologous wild-type allele (10-14), and occur as germ-line events in heritable cases and somatic events in sporadic cases. Several somatic chromosomal mechanisms effect this loss, including nondisjunctional loss of the homolog carrying the wild-type allele, followed by reduplication of the mutant chromosome, and mitotic recombination between the two homologs (10); the net result is a cell that is homozygous for the mutant allele at the RBI locus (14).Advances in surgical and radiotherapeutic techniques have led to survival rates exceeding 90% for retinoblastoma patients. However, survivors of the heritable, but not the spontaneous, form are at a substantially increased risk for the development of independent, second tumors (15)(16)(17)(18)(19)(20). In a recent longitudinal survey of 693 bilateral retinoblastoma cases (20), 15% developed independent second pr...

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The Heredity of Retinoblastoma

Cited by 98 publications

References 0 publications

Patterns of risk of hereditary retinoblastoma and applications to genetic counselling

Patterns of risk of hereditary retinoblastoma and applications to genetic counselling

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862-1994

Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition.

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