Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice

Abstract

The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

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

“…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. 47 We believe that monitoring is worthwhile at least in UPD patients, given their high risk of hepatoblastoma.…”

WT1 in disease: shifting the epithelial–mesenchymal balance

“…Denys-Drash syndrome (DDS) constitutes a triad of Wilms' tumour, rapidly progressive renal disease, and ambiguous genitalia or pseudo-hermaphroditism in males [59,60]. It is caused by point mutations in the zinc fingers of WT1, usually missense mutations located within exons 8 or 9, coding for zinc fingers 2 or 3.…”

Clinical utility gene card for: Beckwith–Wiedemann Syndrome

“…However, the risk of WT varies according to the molecular subtype 2,14,15 and some centres adjust screening protocols to reflect this 16 , for example, in the case of ICR1 hypermethylation, dup(11p)pat and UPD(11p15)pat, screening may be more intensive; AFP screening is advised and scanning may continue until adolescence. Current evidence from cohort studies suggests that ICR2 hypomethylation and CDKN1C mutations are not associated with increased risk for WT, though increased risk for hepatoblastoma cannot be discounted.…”