Epigenotype, phenotype, and tumors in patients with isolated hemihyperplasia.

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.