New Dental Phenotypes And Related Genotypes In Nine CCD Patients

Cleidocranial dysplasia (CCD) is a rare genetic disorder characterized by clavicle hypoplasia, delayed fontanelle closure, and dental anomalies. RUNX2 is the pathogenic gene of CCD, and there are few studies to identify whether different RUNX variants show the certain tooth phenotypes. This study aims to address the genotype-phenotype correlations in dental anomalies. Nine CCD patients were recruited and performed the clinical examination, radiographicial examination and pedigree analysis. Whole genome analysis or whole exome analysis were used to screen out the pathogenic gene, and PCR and Sanger sequencing were applied to identify the variants. The detailed tooth phenotypes were compared among the cases with different RUNX2 mutations, especially about the impacted or embedded teeth and surrounding tissues. 20 individuals with the impacted third molars or canines were chosen as controls. Besides the well known retained deciduous teeth, delayed eruption of permanent teeth and supernumerary teeth, the new and unique spatiotemporal changes in crown, root, periodontal ligament, as well as dental sac and surrounding bone tissues were also found in the CCD impacted or embedded teeth. The nine CCD cases carried four missense, one splicing and four frameshift/nonsense mutations. The later cause severe dental phenotypes especially in impacted teeth. The emerging time, location and number of supernumerary teeth varied with the mutations. The spatiotemporal characteristics of the impacted/embedded permanent teeth and supernumerary teeth and their genetic background may help to determine the suitable treatment time and strategy.