Diagnosis of Beckwith–Wiedemann syndrome in children presenting with Wilms tumor

Abstract

Beckwith-Wiedemann syndrome (BWS) is a genetic syndrome associated with overgrowth and cancer predisposition, including predisposition to Wilms tumor (WT). Patients with BWS and BWS spectrum are screened from birth to age 7 years for BWS-associated cancers. However, in some cases a BWS-associated cancer may be the first recognized manifestation of the syndrome. We describe 12 patients diagnosed with BWS after presenting with a WT. We discuss the features of BWS in these patients and hypothesize that earlier detection of BWS by attention to its subtler manifestations could lead to earlier detection of children at risk for associated malignancies.

11p15.5 epimutations in children with Wilms tumor and hepatoblastoma detected in peripheral blood

“…The current study evaluated methylation abnormalities affecting the imprinted region at 11p15.5 in children with the 2 most commonly associated tumors. The data presented in the current study have expanded on previous work demonstrating that Wilms tumor can be the presenting sign of epimutations associated with BWSp 17 . Further work should be done in larger cohorts of patients with Wilms tumor and hepatoblastoma to determine the efficacy of screening all patients with these tumors for 11p15.5 epimutations.…”

“…Her results were very similar to those of the other females with bilateral Wilms tumors despite her blood draw for BWS testing occurring >30 years after her diagnosis. In addition, MacFarland et al did not find any evidence of circulating tumor DNA in the blood in their cohort, despite many positive results in other tissues 17 …”

“…To our knowledge, the current study cohort differs from Wilms tumor cohorts described previously 17,31 in that all patients in the current study cohort were found to have epimutations on analysis from peripheral blood, whereas patients in the prior cohorts were identified through testing blood, skin, tumor, and healthy kidney, and did not include patients with hepatoblastoma. The most notable difference with regard to the findings of the current study was that none of the patients in our cohort were found to have pUPD, whereas in the study by MacFarland et al 17 approximately one‐half of the cohort was diagnosed with mosaic pUPD. However, the 5 patients in the current study with complete or partial loss of heterozygosity of chromosome 11 detected in tumor may have been somatic mosaic for this abnormality if other samples were analyzed because pUPD is especially likely to be mosaic.…”

“…BWS recently has been redefined as the Beckwith‐Wiedemann spectrum (BWSp), which is especially broad, most likely due to the frequent somatic (rather than predominantly germline) occurrence of underlying epigenetic alterations, often resulting in mosaic results across various tissues 11,16 . For example, outside of patients who clearly are syndromic, it has been shown that Wilms tumor can be the presenting sign of BWSp in children who either are without other signs or with subtle other signs that were not previously realized to be related 17,18 . Isolated lateralized overgrowth (also known as hemihypertrophy and/or hemihyperplasia) has long been recognized to be associated with a predisposition toward Wilms tumor and hepatoblastoma, regardless of whether a detectable genetic or epigenetic mutation is present 19 .…”

Beckwith–Wiedemann syndrome in diverse populations

“…A total of 139 patients were included for analysis. To our knowledge, only 32 of these patients have previously been reported (Kalish et al, ; MacFarland et al, , ; Peterson et al, ; Tong et al, ). Characteristics about diagnosis including the age at diagnosis and indications for diagnosis were evaluated for differences between the three groups (Caucasian, Mixed, non‐Caucasian) within the current cohort.…”