Increased paternal age at conception and a similar bias in the parental origin of de novo HRAS mutations have been documented in patients with Costello syndrome.32, 33 For the five cases with de novo LZTR1 mutations described here, paternal ages at childbirth were also elevated (mean = 35.8, Table S5) compared with the average across this DDD datafreeze (mean = 32.6). Here, HRAS is linked to Costello syndrome.