Epigenotype, phenotype, and tumors in patients with isolated hemihyperplasia

J Pediatr. 2008 Jul;153(1):95-100. doi: 10.1016/j.jpeds.2007.12.022. Epub 2008 Mar 7.

Abstract

Objective: To investigate whether epigenotyping of patients with isolated hemihyperplasia (IH) can, analogous to genetic screening of patients with Beckwith-Wiedemann syndrome, be used for the prediction of tumor risk and tumor type of individual patients.

Study design: Methylation analysis of H19 and KCNQ1OT1 of 73 patients. Questionnaires were sent to referring clinicians.

Results: In 75% of the clinically confirmed patients with IH no epigenetic defect was detected. Paternal uniparental disomy was found in 15%, demethylation of KCNQ1OT1 in only 6%, and hypermethylation of H19 in 3% of isolated hemihyperplasia cases. Ten percent of the patients with IH had development of a childhood tumor associated with paternal uniparental disomy (2/8) or no methylation defect (2/30). No genetic defect was detected in 10 of 14 additional patients with cancer with IH. In these latter patients, a methylation defect of H19 was seen 3 times and a paternal uniparental disomy once. The female-to-male ratio was 6:1.

Conclusions: Aberrant methylation of the 11p15 region is not common in patients with IH and can at present not be used for tumor risk determination.

MeSH terms

  • Beckwith-Wiedemann Syndrome / complications*
  • Beckwith-Wiedemann Syndrome / genetics*
  • Child
  • Child, Preschool
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Genotype
  • Humans
  • Infant
  • Male
  • Models, Genetic
  • Neoplasms / complications*
  • Neoplasms / genetics
  • Phenotype
  • Risk Factors
  • Uniparental Disomy