RREB1 and Noonan syndrome: Rreb1+/− mice were slightly smaller with a wider blunted nose and significantly increased intercanthal distance (ICD, p < 0.001 t-test) compared to WT littermates (Fig. 2b–d and Supplementary Fig. 2c, d) similar to the changes in the cranial bones observed in the Noonan syndrome mouse model25.