SFRP4 and Pyle disease: Mouse clavicles, ribs, digits, and the cranial base, sites with radiographic abnormalities in Pyle’s subjects, have not been examined as all mouse studies were performed prior to the 2016 identification of SFRP4 mutations being responsible for Pyle’s disease.9 During development growth plates (synchondroses) separate the sphenoid, ethmoidal and basioccipital bones at the base of the skull.44 Presumably, disturbances in metaphyseal bone modeling similar to those observed in limbs is responsible for cranial base sclerosis observed in Pyle’s disease subjects.