The primary site of the acrocephalic feature in Apert syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling

► Expression of Apert-type mutant Fgfr2IIIc in chondrocytes reproduced acrocephaly. ► Upregulation of p21, Ihh, Mmp-13 indicated acceleration of endochondral ossification. ► The acrocephalic feature is not alone a result of the coronal synostosis. ► It is primarily due to the precocious endochondral ossification in the cranial base.