There is an extremely wide range of clinical manifestations (even within the same family) from isolated dental anomalies to severe malformations with functional repercussions. The main clinical signs are hypoplasia or aplasia of the clavicles with narrow, sloping shoulders that can be approximated anteriorly, delayed fusion of cranial sutures with large, wide-open fontanels at birth that may persist throughout life, and a wide spectrum of dental anomalies including abnormal dentition, uniform or chaotic supernumerary teeth (hyperdontia) in the primary and secondary dentition resulting in crowding and malocclusion, retention of deciduous teeth, delayed eruption of secondary dentition and failure to shed the primary teeth. The dental manifestations may affect articulation and mastication. Other signs include broad flat forehead, hypertelorism, midface hypoplasia, and a pointed jaw giving a characteristic facial appearance as well as brachydactyly, tapering fingers and short, broad thumbs.
CCD is caused by mutations in the RUNX2 gene (6p21) involved in differentiation of osteoblasts and bone formation. A wide range of mutations have been identified, with high penetrance and significant variability. No clear phenotype-genotype correlations have been established.
