Background RUNX2 can act as both oncogene and tumour suppressor. In cleidocranial dysplasia (CCD), RUNX2 mutations cause haploinsufficiency of the protein. We encountered a young man with CCD who developed lymphoma at age 16 years and melanoma in his early 20s. Sequencing of RUNX2 identified a novel, damaging and conserved missense mutation (p. Arg186Ile) not present in either parent.

Objectives We sought evidence to support or refute a greater than expected cumulative incidence of paediatric cancer in CCD.

Design/method We reviewed English language descriptions of individuals with CCD to identify the proportion with paediatric cancer. We compared this frequency to the expected background frequency of cancer in the paediatric age range. We also performed a sensitivity analysis to determine a reporting bias threshold at which a perceived association would be spurious.

Results Six of 1242 individuals with CCD had paediatric cancer. One would expect only 1 in 6250 individuals to have cancer prior to age 20 (SEER CDC data). The estimated relative risk is 30-fold based on this data. If, however, a co-occurrence of CCD and paediatric cancer is 15 times more likely to be reported in the literature than an occurence without cancer, then the observation of increased relative risk is spurious.

Conclusions Our data suggests a role for RUNX2 in some paediatric cancers and a possible increased relative risk, but low absolute risk, for cancer in CCD. A CCD registry with prospective data collection may be the best means to determine actual risk of paediatric cancer in CCD.