Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS)

J Pediatr. 2004 Dec;145(6):796-9. doi: 10.1016/j.jpeds.2004.08.007.


Objectives: Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms' tumors. Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases. Our aim was to determine associations between the imprinting status of both imprinting clusters (BWSIC1/2) and the tumor incidence and type.

Study design: Methylation patterns of H19 and KCNQ1OT1 were collected in 114 patients with BWS with a clinical diagnosis. The patients were followed until 5 years of age, and tumor incidence and type were registered.

Results: A lower risk of developing childhood tumors was found among patients with a methylation defect limited to BWSIC2 compared with other patients with BWS. No Wilms' tumors were found in this group, whereas in patients with a methylation defect limited to BWSIC1 Wilms' tumor was the most common tumor.

Conclusions: In addition to clinical factors indicative for a high tumor risk (hemihypertrophy, nephromegaly), methylation patterns discriminate between patients with BWS with a high and low tumor risk. It also is possible to predict whether they are at risk of developing a Wilms' tumor. Epigenotyping of patients is important to select the type of screening protocol to be proposed to these patients.

Publication types

  • Comment

MeSH terms

  • Beckwith-Wiedemann Syndrome / complications
  • Beckwith-Wiedemann Syndrome / genetics*
  • Child, Preschool
  • France / epidemiology
  • Genes, Wilms Tumor*
  • Genotype
  • Humans
  • Incidence
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / genetics*
  • Membrane Proteins / genetics*
  • Membrane Proteins / isolation & purification
  • Methylation
  • Neoplasms / classification
  • Neoplasms / epidemiology*
  • Netherlands / epidemiology
  • Potassium Channels, Voltage-Gated / genetics*
  • Potassium Channels, Voltage-Gated / isolation & purification
  • Predictive Value of Tests
  • Risk Factors
  • Wilms Tumor / etiology
  • Wilms Tumor / genetics*


  • KCNQ1OT1 long non-coding RNA, human
  • Membrane Proteins
  • Potassium Channels, Voltage-Gated