Screening for Wilms tumor and hepatoblastoma in children with Beckwith‐Wiedemann syndromes: A cost‐effective model*

McNeil, D. Elizabeth; Brown, M L; Ching, Alexander C.; DeBaun, Michael R.

doi:10.1002/mpo.1209

Cited by 79 publications

(46 citation statements)

References 19 publications

(21 reference statements)

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“…At present, cancer surveillance programs for BWS patients are based on a 3-6 months abdominal ultrasound up to 7-8 years of age to detect Wilms' tumor and 2-3 months serum alpha-fetoprotein determinations up to 4 years of age to screen for hepatoblastoma. 4 Cost-effectiveness of ultrasound screening is proven; 43 we hypothesize that patients with IC1-GoM may benefit from an intensification of abdominal ultrasound during the first Phenotypes in Beckwith-Wiedemann syndrome A Mussa et al 3 years of life, as most of Wilms' tumors are diagnosed before that age and appears justified by their 25% chance of developing a Wilms' tumor, the well-proven beneficial effect of early diagnosis, and the low invasivity of abdominal ultrasound. 44 Conversely, the dosage of the tumor marker serum alpha-fetoprotein as a screening method for the early diagnosis of hepatoblastoma is debated, given the complexity of its interpretation in childhood, 45,46 the low incidence of hepatoblastoma and the invasivity of frequent blood drawns, which is commonly responsible for the lack of adherence to screening protocols.…”

Section: Phenotypes In Beckwith-wiedemann Syndromementioning

confidence: 96%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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Beckwith-Wiedemann syndrome (BWS) is characterized by cancer predisposition, overgrowth and highly variable association of macroglossia, abdominal wall defects, nephrourological anomalies, nevus flammeus, ear malformations, hypoglycemia, hemihyperplasia, and organomegaly. BWS molecular defects, causing alteration of expression or activity of the genes regulated by two imprinting centres (IC) in the 11p15 chromosomal region, are also heterogeneous. In this paper we define (epi)genotype-phenotype correlations in molecularly confirmed BWS patients. The characteristics of 318 BWS patients with proven molecular defect were compared among the main four molecular subclasses: IC2 loss of methylation (IC2-LoM, n = 190), IC1 gain of methylation (IC1-GoM, n = 31), chromosome 11p15 paternal uniparental disomy (UPD, n = 87), and cyclin-dependent kinase inhibitor 1C gene (CDKN1C) variants (n = 10). A characteristic growth pattern was found in each group; neonatal macrosomia was almost constant in IC1-GoM, postnatal overgrowth in IC2-LoM, and hemihyperplasia more common in UPD (Po0.001). Exomphalos was more common in IC2/CDKN1C patients (Po0.001). Renal defects were typical of UPD/IC1 patients, uretheral malformations of IC1-GoM cases (Po0.001). Ear anomalies and nevus flammeus were associated with IC2/CDKN1C genotype (Po0.001). Macroglossia was less common among UPD patients (Po0.001). Wilms' tumor was associated with IC1-GoM or UPD and never observed in IC2-LoM patients (Po0.001). Hepatoblastoma occurred only in UPD cases. Cancer risk was lower in IC2/CDKN1C, intermediate in UPD, and very high in IC1 cases (P = 0.009).In conclusion, (epi)genotype-phenotype correlations define four different phenotypic BWS profiles with some degree of clinical overlap. These observations impact clinical care allowing to move toward (epi) genotype-based follow-up and cancer screening.

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Section: Phenotypes In Beckwith-wiedemann Syndromementioning

confidence: 96%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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“…Therefore, focused surveillance on the types of cancer(s) to which the individual is most predisposed, and during the period of greatest risk, should substantially improve their outcome through early detection. Indeed, many centers are starting to follow proposed early tumor surveillance protocols that have been published for a few disorders like Li-Fraumeni Syndrome (LFS) and BWS-hemihypertrophy (8–10). However, even for these disorders, surveillance has not been performed consistently across different centers, and there are still many inherited cancer predisposition disorders for which either no protocols, or multiple published protocols, exist.…”

Section: Pediatric Cancer Predisposition: Introductionmentioning

confidence: 99%

Pediatric Cancer Predisposition and Surveillance: An Overview, and a Tribute to Alfred G. Knudson Jr

Brodeur

Nichols

Plon

et al. 2017

Clinical Cancer Research

144

110

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The prevalence of childhood cancer attributable to genetic predisposition was generally considered very low. However, recent reports suggest that at least 10% of pediatric cancer patients harbor a germline mutation in a cancer predisposition gene. Although some of these children will have a family history suggestive of a cancer predisposition syndrome, many others will not. Evidence from recent pediatric studies suggests that surveillance and early detection of cancer in individuals carrying a germline cancer predisposing mutation may result in improved outcomes. However, there is a lack of consistency in the design of cancer surveillance regimens across centers nationally and internationally. To standardize approaches, the Pediatric Cancer Working Group of the American Association for Cancer Research (AACR) convened a workshop, during which consensus screening recommendations for children with the most common cancer predisposition syndromes were developed. In general, we considered a 5% or greater chance of developing a childhood cancer to be a reasonable threshold to recommend screening. Conditions for which the cancer risk was between 1 to 5% were addressed individually. In a series of manuscripts accompanying this article, we provide recommendations for surveillance, focusing on when to initiate and/or discontinue specific screening measures, which modalities to use, and the frequency of screening. Points of controversy are also reviewed. We present the outcome of our deliberations for consensus screening recommendations for specific disorders in 18 position papers as Open Access publications and available on an AACR-managed web site.

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“…Screening at these short intervals increased the number of stage I and II Wilms' tumors detected, hence favoring the outcome of children with BWS with malignant tumors. [11][12][13][14] The genes involved in BWS are located on chromosome 11p15 and are subject to genomic imprinting. Within this region there are two imprinting domains, each controlled by its own imprinting center; BWS imprinting center 1 (BWSIC1, telomeric domain) and BWS imprinting center 2 (BWSIC2, centromeric domain).…”

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confidence: 99%