Background: Retinoblastoma is the most common intraocular malignancy in childhood and is responsible for approximately 1% of all deaths caused by childhood cancer. Aims/methods: Comparative genomic hybridisation was performed on 13 consecutive, histologically confirmed retinoblastomas to analyse patterns of chromosomal changes and correlate these to clinicopathological variables. Six cases were hereditary and seven cases were sporadic. Results: In 11 of the 13 tumours chromosomal abnormalities were detected, most frequently gains. Frequent chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q, and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%). High level copy number gains were found at 5p15 and 6p11-12. A loss at 13q14 occurred in three cases only. Relatively few events occurred in the hereditary cases (27) compared with the non-hereditary cases (70 events). The number of chromosomal aberrations in these 13 retinoblastomas showed a bimodal distribution. Seven tumours showed less than four chromosomal aberrations, falling into a low level chromosomal instability (CIN) group, and six tumours showed at least eight aberrations, falling into a high level CIN group. In the low level CIN group the mean age was half that seen in the high level CIN group, there were less male patients, and there were more hereditary and bilateral cases. Microsatellite instability was not detected in either of the two groups. Conclusion: Despite the complex pattern of genetic changes in retinoblastomas, certain chromosomal regions appear to be affected preferentially. On the basis of the number of genetic events, retinoblastomas can be divided in low and a high level chromosomal instability groups, which have striking differences in clinical presentation.

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...

Little is known about the reproductive decision-making process of couples with an increased risk of having a child with retinoblastoma (Rb). A qualitative study was conducted to explore the impact of prospective risk on reproductive decisions, factors influencing these decisions, and the needs of couples with regard to reproductive counselling. Fourteen couples of childbearing age who received genetic counselling between 2002 and 2006 participated in semi-structured interviews in 2008. The risk of having a child with Rb ranged from less than 1% to 50%. In most cases, the diagnosis of Rb influenced subsequent family planning. Prenatal diagnosis was used by two couples, while others refrained from having more children. Reproductive decisions were influenced by the burden of the disease for the patient and family members, the impact of ophthalmological screening under anaesthesia, and couples' perceived risk, which did not always relate to their actual risk. Reproductive choices with regard to the number of children wanted changed over time. Our findings indicate topics to be discussed during genetic counselling of couples at increased risk for a child with Rb. We suggest continued access to genetic counselling also after the initial diagnosis and treatment.

SUMMARY:We report a 6-month-old boy who presented with unilateral leukocoria, retinal detachment, and a retrolental mass in a microphthalmic eye based on retinal dysplasia with concurrent optic nerve aplasia. Dysplastic retinal tissue, a rare congenital defect, may create a clinical and radiologic picture of an intraocular mass closely resembling tumor tissue. MR imaging findings with histopathologic correlation are presented to facilitate discrimination of the more common causes of leukocoria. Retinal dysplasia is a rare cause of childhood leukocoria, which can cause considerable diagnostic difficulty in the differentiation of benign and malignant intraocular pathology. When clinical diagnosis is uncertain, ocular MR imaging helps to characterize and differentiate between intraocular pathologies. However, in contrast to many lesions in the differential diagnosis of leukocoria, to our knowledge, detailed MR imaging findings in retinal dysplasia have not been previously reported. We report MR imaging findings of unilateral retinal dysplasia with concurrent optic nerve aplasia. Case ReportA 6-month-old boy was admitted with a history of a smaller left eye since birth and leukocoria for 1 month. He was born to nonconsanguineous parents at 41 weeks' gestation. Ophthalmic examination revealed no abnormalities in the right eye. The left eye was microphthalmic, with a corneal diameter of 9 mm (right, 10 mm). A yellowish-white retrolental mass, projecting from the inferomedial quadrant into the vitreous, was present (Fig 1). The mass in combination with retinal detachment obscured clear visualization of optic nerve disc and macula. Prominent irregular feeder vessels and small focal hemorrhages covered the surface of the mass. Differential diagnosis based on these findings included ciliary body medulloepithelioma, anteriorly located retinoblastoma, and persistent hyperplastic primary vitreous (PHPV).Ultrasonography showed a noncalcified mass with high reflectivity. MR imaging showed a mass arising from the nasal ciliary body region with high signal intensity (SI) on T1-weighted (T1WI) and low SI on T2-weighted (T2WI) images, combined with a normal-appearing vitreous and tent-shaped retinal detachment with subretinal exudate (Fig 2). The anterior chamber and lens showed no abnormalities. The right orbit, optic nerve, and portions of the optic chiasm related to the nerve were normal. The optic nerve and sheath complex were not visible within the left orbit or anywhere along the usual course of the nerve (Fig 2). Total aplasia of the left optic nerve was not combined with other congenital central nervous system (CNS) abnormalities. The mass showed intense homogeneous enhancement. Ultrasonography and MR imaging findings were more consistent with medulloepithelioma or PHPV, and a retinoblastoma could be ruled out. Five weeks later, enucleation was required due to enlargement of the mass with an increase of intraocular pressure, shallowness of the anterior chamber, and progression toward a phthisis bulbi.Histopathologic examin...

To investigate reproductive behavior of individuals at increased risk of having a child with retinoblastoma (Rb), we conducted a cross-sectional questionnaire survey among 118 counselees visiting the Clinical Genetics Department of the National Rb Center in the Netherlands. The recurrence risk for counselees ranged from <1% to 50%. The response rate was 69%. Of 43 respondents considering having children after becoming aware of their increased risk, Rb influenced reproductive behavior for 25 (58%), of whom 14 had a recurrence risk <3%. Twenty of these 25 decided against having more children and 5 used prenatal diagnosis. Eighteen of the 43 respondents did not use any of the alternative reproductive options and had children (or more children), although half indicated having had doubts about their decisions. Multiple logistic regression showed that only perceived risk (p = 0.003) was significantly associated with Rb influencing reproductive behavior. Of 17 respondents planning children (or more children), 11 (65%) considered using one of the alternative reproductive options. We conclude that reproductive behavior is greatly influenced by Rb and that perceived risk, not objective risk, is the most important factor of influence. It is important to offer individuals at increased risk continued access to genetic counseling, even when this risk is small.