Genetics of retinoblastoma. 1979

F Vogel

The genetic basis of retinoblastoma is reviewed and the following conclusions are drawn: 1) The mode of inheritance of the hereditary variety of retinoblastoma (R) is autosomal dominant with about 90% penetrance. 2) About 68% of inherited cases are bilateral, and about 32%, unilateral. There is an intrafamilial correlation between penetrance as measured by segregation ratio and expressivity as measured by the fraction of bilaterally affected patients. 3) The vast majority of all R patients are sporadic cases, i.e., they are the only affected members of otherwise unaffected families. The porportion of bilateral cases is much lower among sporadic than among hereditary cases. 4) All bilaterally affected patients with sporadic R and patients with unilateral sporadic R with more than one primary tumor have to be regarded as germ cell mutants; they will transmit the gene to 50% of their offspring. Only 10%-12% of unilateral sporadic cases are germ cell mutants; 88%-90% are nonhereditary; in these cases the tumor is probably caused by a somatic mutation. 5) In a minority of cases, deletion of the chromosome segment 13q14(=intersitital deletion of the long arm of chromosome 13) has been observed. In addition to R, the patients show a variable degree of general or mental retardation; often there are few external indications of a chromosome aberration. Other chromosome studies suggest anomalies of chromosome 13 in tumor tissue even in cases not showing an anomaly of this chromosome in blood cultures, and possibly a slightly increased chromosome instability. 6) Patients with bilateral, and possibly in general with hereditary, R run an increased risk of becoming affected with other tumor diseases, such as osseous sarcomas, in later life. 7) Knudson's hypothesis of two mutational steps leading to both the hereditary and the nonhereditary variants of R is discussed critically, and the alternative possibility is suggested that in the nonhereditary variant a single mutational step--possibly a small chromosome aberration--could be enough to produce a tumor. 8) Evidence indicating a possible viral origin of R is cited, and animal experiments are mentioned in which R-like tumors have successfully been produced by local DNA virus inoculation. 9) As a consequence of improved survival and reproduction of R patients, an increased in the incidence of R and in the proportion of bilateral cases among all R patients must be anticipated. 10) Detailed rules for genetic counseling in families affected by R are given.

UI MeSH Term Description Entries
D008297 Male Males
D008607 Intellectual Disability Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28) Disability, Intellectual,Idiocy,Mental Retardation,Retardation, Mental,Deficiency, Mental,Intellectual Development Disorder,Mental Deficiency,Mental Retardation, Psychosocial,Deficiencies, Mental,Development Disorder, Intellectual,Development Disorders, Intellectual,Disabilities, Intellectual,Disorder, Intellectual Development,Disorders, Intellectual Development,Intellectual Development Disorders,Intellectual Disabilities,Mental Deficiencies,Mental Retardations, Psychosocial,Psychosocial Mental Retardation,Psychosocial Mental Retardations,Retardation, Psychosocial Mental,Retardations, Psychosocial Mental
D009378 Neoplasms, Multiple Primary Two or more abnormal growths of tissue occurring simultaneously and presumed to be of separate origin. The neoplasms may be histologically the same or different, and may be found in the same or different sites. Neoplasms, Synchronous,Neoplasms, Synchronous Multiple Primary,Multiple Primary Neoplasms,Multiple Primary Neoplasms, Synchronous,Synchronous Multiple Primary Neoplasms,Synchronous Neoplasms,Multiple Primary Neoplasm,Neoplasm, Multiple Primary,Neoplasm, Synchronous,Primary Neoplasm, Multiple,Primary Neoplasms, Multiple,Synchronous Neoplasm
D010331 Paternal Age Age of the biological father. Age, Paternal,Ages, Paternal,Paternal Ages
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002872 Chromosome Deletion Actual loss of portion of a chromosome. Monosomy, Partial,Partial Monosomy,Deletion, Chromosome,Deletions, Chromosome,Monosomies, Partial,Partial Monosomies
D002901 Chromosomes, Human, 13-15 The medium-sized, acrocentric human chromosomes, called group D in the human chromosome classification. This group consists of chromosome pairs 13, 14, and 15. Chromosomes D,Group D Chromosomes,Chromosome, Group D,Chromosomes, Group D,Group D Chromosome
D005134 Eye Neoplasms Tumors or cancer of the EYE. Cancer of Eye,Eye Cancer,Cancer of the Eye,Neoplasms, Eye,Cancer, Eye,Cancers, Eye,Eye Cancers,Eye Neoplasm,Neoplasm, Eye
D005260 Female Females
D005799 Genes, Dominant Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state. Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant

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