Sphenoid bone hypoplasia is a skeletal phenotype of cleidocranial dysplasia in a mouse model and patients.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by heterozygous mutations in RUNX2. Affected individuals exhibit delayed maturation or hypoplasia in various bones, mainly including those formed by intramembranous ossification. Although several reports described deformation of the sphenoid bone in CCD patients, details of the associated changes have not been well documented. Most parts of the sphenoid bone are formed by endochondral ossification; however, the medial pterygoid process is formed by intramembranous ossification associated with secondary cartilage. We first investigated histological changes in the medial pterygoid process during different developmental stages in Runx2+/+ and Runx2+/- mice, finding that mesenchymal cell condensation of the anlage of this structure was delayed in Runx2+/- mice as compared with that in Runx2+/+ mice. Additionally, in Runx2+/+ mice, Osterix-positive osteoblastic cells appeared at the upper region of the anlage of the medial pterygoid process, and bone trabeculae appeared to associate with subsequent secondary cartilage formation. By contrast, few Osterix-positive osteoblastic cells appeared at the upper region of the anlage of the medial pterygoid process, and no bone trabeculae appeared thereafter in Runx2+/- mice. At more advanced embryonic stages, endochondral ossification occurred at the lower part of the medial pterygoid process in both Runx2+/+ and Runx2+/- mice. After birth, well-developed bone trabeculae occupied two-thirds of the cranial side of the medial pterygoid process, and cartilage appeared beneath these bones in Runx2+/+ mice, whereas thin trabecular bone appeared at the center of the cartilage of the medial pterygoid process in Runx2+/- mice. In adult mice, the body and medial pterygoid processes of the sphenoid bone comprised mature bones in both Runx2+/+ and Runx2+/- mice, although the axial length of the medial pterygoid processes was apparently lower in Runx2+/-mice as compared with that in Runx2+/+mice based on histological and micro-computed tomography (CT) examinations. Moreover, medical-CT examination revealed that in CCD patients, the medial pterygoid process of sphenoid bone was significantly shorter relative to that in healthy young adults. These results demonstrated that the medial pterygoid process of the sphenoid bone specifically exhibited hypoplasia in CCD.