[Cleidocranial dysplasia. Description and analysis of a patient cohort].

Background: Cleidocranial dysplasia (CCD) is a rare dysplasia of bony and dental tissue. Characteristic are typical craniofacial and dental findings including morphological anomalies. CCD is possibly the only general syndrome that can be diagnosed based on the dental findings alone. CCD correlates with mutations in the RUNX2 gene.

Purpose: The present interdisciplinary study correlates phenotypic findings with genetic variations in the corresponding gene.

Patients and methods: The coding sequence of the RUNX2 gene from 31 CCD patients from 20 families was analyzed using molecular genetic methods including polymerase chain reaction and direct sequencing. The craniofacial and dental findings of each patient were evaluated according to a standardized scoring scheme and tested with homogeneity analysis for general phenotypic findings.

Results: Several mutations of the RUNX2 gene were identified. Depending on the mutation type, they showed different distribution patterns within the gene coinciding with the functional domains of the gene product. With homogeneity analysis of the phenotype cardinal (especially dental findings) and minor findings (pneumatization disturbances, Wormian bones) were identified. In combination with the genetic data, the statistical analysis showed that loss-of-function mutations of the RUNX2 gene result in a milder markedness of the CCD phenotype than gain-of-function or decrease-of-function mutations.

Conclusions: We found that type and location of a specific mutation within the RUNX2 gene might have an impact on the expressivity of CCD. Due to the limited sampling size this hypothesis must be verified by investigations in larger patient groups.