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Summary: Tumor predisposition in children is rare, accounting for approximately 10% of all cancers in childhood. Tumor predisposition involves very rare tumors such as pleuropulmonary blastoma, adrenocortical carcinoma, hepatoblastoma, rhabdoid tumors, optic pathway glioma, as well as rare tumors such as retinoblastoma, medulloblastoma, nephroblastoma, or more frequent tumors such as sarcomas, neuroblastoma, and leukemias. The identification of these predispositions is important for improved management for both the child and relatives. Prenatal and preimplantation genetic diagnosis are options that could be considered for young parents in a perspective of future pregnancies. This manuscript describes the main tumor predispositions in childhood. From each histological subtype, the different diagnosis directions are discussed in view of these main tumor predispositions. [ABSTRACT FROM AUTHOR]

Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of 2 years, and in most cases they are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of 1 year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10-15% of children with a unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms at diagnosis are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, location), the risks for vision, and the possible hereditary nature of the disease. The main prognostic aspects are still early detection and adapted coverage by a multidisciplinary, highly specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is made according to the histological risk factors. The most important recent therapeutic advances concern conservative treatment, which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy, or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion and intravitreal injections, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblastoma is now excellent in industrialized countries, but long-term survival is still related to the development of secondary tumors, mainly secondary sarcoma. Retinoblastoma requires multidisciplinary care as well as a long-term specialized follow-up. Early counseling of patients and their family concerning the risk of transmission of the disease and the risk of development of secondary tumors is necessary. [ABSTRACT FROM AUTHOR]

Retinoblastoma is the most frequent malignant tumour in children with an incidence of 1 in 15,000 live births. Sixty per cent of retinoblastoma cases involve one eye (unilateral):median age at diagnosis is 2 years, and most of these forms are non-hereditary. Forty percent of retinoblastoma cases are bilateral: the median age at diagnosis is 1 year. All bilateral and multifocal unilateral forms are hereditary. Hereditary retinoblastoma is a cancer predisposition syndrome: the presence of a constitutional RB1 gene mutation in patients implies they have a greater than 90% chance of developing retinoblastoma. They also have an increased risk of developing other types of cancer. Leucocoria and strabismus are the most frequent revealing symptoms. Diagnosis is made by fundoscopy. US, MRI and CT scans may contribute to diagnosis. Treatment of patients with retinoblastoma should take into account the various aspects of the disease: the risk to vision, the possible hereditary nature of the disease, the life threatening risk. Enucleation is still often necessary in unilateral disease; adjuvant treatment might be given according to histological risk factors. Conservative treatmentmay be to at least one eye in most of bilateral cases: thermotherapy combined with chemotherapy, cryotherapy and brachytherapy. External beam radiation therapy should be restricted to large ocular tumours and diffuse vitreous seeding ocular because of the risk of late effects, including secondary sarcoma. Long term follow-up of patients with retinoblastoma is important, as well as information given at an early stage to them and their family about the risks of second primary tumours and of transmission to their off springs. [ABSTRACT FROM AUTHOR]

Background: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with an increased risk of pediatric tumors. The underlying molecular abnormalities may be genetic (CDKN1C mutations or 11p15 paternal uniparental isodisomy, pUPD) or epigenetic (imprinting center region 1, ICR1, gain of methylation, ICR1 GOM, or ICR2 loss of methylation, ICR2 LOM). Aim: We aimed to describe a cohort of 407 BWS patients with molecular defects of the 11p15 domain followed prospectively after molecular diagnosis. Results: Birth weight and length were significantly higher in patients with ICR1 GOM than in the other groups. ICR2 LOM and CDKN1C mutations were associated with a higher prevalence of exomphalos. Mean adult height (regardless of molecular subtype, n = 35) was 1.8 ± 1.2 SDS, with 18 patients having a final height above +2 SDS. The prevalence of tumors was 8.6% in the whole population; 28.6 and 17.3% of the patients with ICR1 GOM (all Wilms tumors) and 11p15 pUPD, respectively, developed a tumor during infancy. Conversely, the prevalence of tumors in patients with ICR2 LOM and CDKN1C mutations were 3.1 and 8.8%, respectively, with no Wilms tumors. Conclusion: Based on these results for a large cohort, we formulated guidelines for the follow-up of these patients according to the molecular subtype of BWS. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background:The effect of BRCA1/2 gene test result on anxiety, depression, cancer-related thought intrusion or avoidance and perceived control over cancer risk was assessed in breast cancer (BC) patients, according to their perceived probability of genetic predisposition to cancer.Methods:Two hundred and forty-three (89% response rate) women with BC completed questionnaires after an initial genetic counselling visit (T1), of which 180 (66%) completed questionnaires again after receiving the BRCA1/2 results (T2). The discrepancy between women's perceived probability of cancer genetic predisposition at T1 and the geneticist's computed estimates was assessed.Results:In all, 74% of women received a negative uninformative (NU), 11% a positive BRCA1/2 and 15% an unclassified variant (UV) result. On hierarchical regression analysis, in women with a positive BRCA1/2 result (vs NU or UV), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted lower levels of anxiety at T2 (β=−0.28; P<0.01), whereas in women receiving a UV result (vs NU or positive BRCA1/2), a lower perceived probability of cancer genetic predisposition than objective estimates at T1 predicted higher levels of anxiety (β=0.20; P<0.01), depression (β=0.19; P<0.05) and intrusion (β=0.18; P<0.05) at T2.Conclusion:The type of BRCA1/2 test result differently affects distress according to women's perceived probability of genetic predisposition before testing. [ABSTRACT FROM AUTHOR]

BACKGROUND Retinoblastoma (RB) is the most frequent eye tumour in children, with an incidence of 1 in 15–20 000 births. It accounts for 11% of all cancers in the first year of life. Except for the hereditary forms, its causes are not well-known. Studies have recently suggested an increased risk of RB among children born after IVF, but the relevant literature is sparse. We assessed the association between infertility treatment, subfertility and RB. METHODS We included all children living in France diagnosed with RB between 1 January 2000 and 31 December 2006 at the Institut Curie, the national reference centre for RB diagnosis and treatment. We used multiple logistic regression to compare them with a national sample of births in France in 1998 and 2003 (n = 28 170). RESULTS The study included 244 non-familial RB cases. The risk of RB increased with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval (CI) 1.33–3.22 at 35–39 years compared with younger than 25 years and adj OR = 2.42, 95% CI 1.22–4.81 at 40 years or older], but the associations with IVF (adj OR = 1.37, 95% CI 0.64–2.95) and ovarian stimulation or intrauterine insemination (adj OR = 1.35, 95% CI 0.77–2.38) were not statistically significant after adjustment for maternal age and tobacco use. Among women who had no infertility treatment, the risk of RB was significantly increased when time to pregnancy exceeded 24 months (adj OR = 2.02, 95% CI 1.17–3.48) compared with time to pregnancy ≤24 months. CONCLUSIONS Our study did not observe a significantly increased risk of RB associated with infertility treatment, in particular with IVF. But we did find an increased risk for women for whom time to pregnancy exceeded 24 months. [ABSTRACT FROM AUTHOR]

AimsTo assess if systematic fundus screening according to an 'intensive' schedule alters ocular outcome and to propose fundus screening schedule guidelines for children related to a retinoblastoma patient.MethodsFor children with a positive family history of retinoblastoma, we perform fundus exams shortly after birth under general anaesthesia and then at regular intervals according to schedules based on the risk. Familial retinoblastoma cases seen at our institution from January 1995 to December 2004 were retrospectively classified as 'screened' or 'non-screened' (NS) and, among the 'screened' patients, as 'intensively screened' (IS) if screening matched our recommendations or 'non-intensively screened' (S). Groups were compared by Fisher exact test for categorical variables and Kruskal-Wallis test for continuous variables.ResultsAmong the 547 retinoblastoma patients managed at our institution during this period, 59 were familial cases. In all, 20 were in the NS group, 23 in the S group, and 16 in the IS group. The number of children enucleated was, respectively, 13, 2, and 0 (P<10−4); external beam radiation (EBRT) was required for, respectively, 6, 0, and 2 children (P<0.009). Chemotherapy burden and visual acuity were not significantly different between groups.ConclusionAn 'intensive' fundus screening schedule decreased the need for enucleation and EBRT. Therefore, despite the heavy burden of the screening schedule, we recommend physicians and health-care professionals to better inform and refer children with a family history of retinoblastoma for genetic counselling and proper fundus screening in specialized centres. [ABSTRACT FROM AUTHOR]