Purpose of study: To investigate the contribution of 11p15 defects to hemi-hypertrophy (HH) and clarify the potential association with Wilms’ tumour.

Methods: Clinical data and blood/DNA samples were collected from patients with hemi- hypertrophy and from their parents. Where normal/abnormal tissue samples were available, fibroblast DNA was also analysed. Recruitment criteria included any patient with growth asymmetry. All patients were analysed for uni-parental disomy of 11p15 by quantitative PCR and for abnormal methylation at imprinting centres 1 and 2 by Pyrosequencing.

Results: Samples from 78 patients, including 30 with a history of a childhood tumour were analysed. Abnormalities at 11p15 were detected in 11 individuals: 9 had uni-parental disomy 11p15; two had isolated hyper-methylation of imprinting centre 1. Four of 11 patients had a history of Wilms’ tumour and one a history of neuroblastoma. The asymmetry and other clinical features in the individuals with 11p15 defects are variable, but often subtle.

Conclusions: HH is a poorly defined term that refers to asymmetrical growth of one region of the body. There is a recognised but poorly defined association with childhood malignancy, particularly Wilms’ tumour. HH is a feature of a number of genetic disorders, including Beckwith-Wiedemann syndrome, which are caused by abnormalities of imprinting at chromosome 11p15. Certain of these defects are associated with an increased risk of Wilms’ tumour. Our data demonstrate that analysis of imprinting at 11p15 in patients with growth asymmetry identifies a subgroup at increased risk of Wilms’ tumour. Tumour surveillance should be encouraged in this group.

Further analyses are required to determine the molecular defects underlying those in whom no 11p15 defect is identifiable. Analyses of paired normal/abnormal tissue samples may be crucial in identifying such abnormalities.