Cleidocranial dysplasia: Clinical overview and genetic considerations

Cleidocranial dysplasia (CCD) is a congenital autosomal dominant syndrome characterised by dental and osseous dysplasia that leads to multiple dental and craniofacial anomalies. Two-thirds of CCD cases are associated with mutations of the runt-related transcription factor 2 (RUNX2) gene which codes for a transcription factor that is responsible for differentiation of osteoblasts and osteoclasts and skeletal development. Multiple mutations have been identified in the Runx2 gene, primarily clustered in the Runt domain. Other genes such as CCAAT/enhancer-binding protein beta (Cebpb) and T-box transcription factor TBX1 (Tbx1) are under investigation. There are multiple clinical and radiological signs of CCD, e.g. brachycephaly, frontal and parietal bossing, open sutures and fontanelles, delayed closure of fontanelles, kyphosis, narrow sloping shoulders, multiple wormian bones, and delayed mineralisation of the skull. Although the signs present themselves in varying degrees, certain signs such as supernumerary teeth, frontal bossing, hypoplastic maxilla, and prognathic mandible are characteristic. However, many of them may not appear before the growth spurt in all cases. Early identification of CCD, especially prenatal ultrasound diagnosis, has a better prognosis as early orthodontic intervention can be commenced. Apart from clinical and radiographic analysis, identification of a RUNX2 mutation can serve as a diagnostic aid in families with a history of CCD. However, it is important to understand that only two-thirds of the people with CCD have RUNX2 mutation, so genetic analysis will not be of use in people without the mutations.