Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for mortality associated with neoplasia, particularly Wilms tumour and hepatoblastoma, but also neuroblastoma, adrenocortical carcinoma, and rhabdomyosarcoma. Some literature reports propose tumour surveillance guidelines based on the molecular alteration detectedrrr whereas others have highlighted the challenges in definitively assigning tumour risk based on molecular classification in BWS.rr The overall estimated risk for tumour development in children with BWS is around 8%,r and the increased risk is concentrated in the first 7 years of life.r Tumour development in affected individuals older than age 7 years is rare, and there is currently no evidence to suggest adults with BWS are at increased cancer risk. Screening is indicated for Wilms tumour and hepatoblastoma due to their high incidence in BWS, and that survival of both tumours is closely related to the clinical stage at the time of diagnosis and the ability to resect the tumour. Abdominal ultrasound is the preferred, simple, tolerated, and cost-effective screening modality for Wilms tumour and hepatoblastoma.r
Wilms tumour
The median age of identification of Wilms tumour is around 2 years.r Children with BWS and Wilms tumour, when compared with non-syndromic children with Wilms tumour, present with less metastatic disease because of earlier stage disease, fewer anaplastic tumours and a higher incidence of bilateral synchronous or metachronous recurrence.r Although patients with BWS and Wilms tumour who are diagnosed using abdominal ultrasound surveillance have a smaller tumour size than children with sporadic Wilms tumour, overall survival values are similar (at least 90% at 4 years).r A scan interval of 3–4 months is recommended, as interval tumours have been reported with scan intervals in excess of 4–6 months, and the rapid Wilms tumour growth rate, with a doubling time estimated to be 11–40 days.r
Hepatoblastoma
Around 90% of hepatoblastomas occur before the age of 4 years, with a median age of 16 months.r Specific studies evaluating hepatoblastoma screening in BWS are lacking, but abdominal ultrasound is the preferred modality, and most screening guidelines recommend 3 monthly ultrasound until the age of 4 years.r It has been suggested ultrasounds should be combined with AFP measurements, as AFP is secreted in >95% of hepatoblastomas and a rising trend is indicative of a hepatoblastoma.r There is insufficient evidence, however, for earlier stage at diagnosis and better prognosis in those who are screened versus unscreened patients. In the paediatric setting, interpreting serum AFP levels is complicated by the wide range and variable concentrations in early infancy. In view of the burden of repeated venepuncture and the complexity of interpreting elevated AFP levels, it has been debated whether the benefits of AFP screening in BWS outweigh the drawbacks.rrrr The international consensus group do not recommend AFP screening as there is no evidence of benefit for screening.r
Neuroblastoma
Although reported in all BWS molecular subgroups, neuroblastomas are preferentially associated with CDKN1C pathogenic variants, with a frequency of ~4%.r Screening for neuroblastomas with urinary vanillylmandelic acid and homovanillic acid and/or the catecholamine:creatinine ratio, combined with three monthly abdominal ultrasounds until age 2 years has been suggested.r However, previous neuroblastoma screening strategies using urinary markers in large-scale population infant settings had a very minor influence on the related morbidity and mortality,r and there is currently no evidence that neuroblastoma screening in BWS improves treatment and survival.