Cleidocranial dysplasia (CCD)

Cleidocranial dysplasia

Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant disorder caused by mutations in the runt-related transcription factor 2 gene (RUNX2, CBFA1). The RUNX2 product is involved in the differentiation of mesenchymal precursor cells towards osteoblasts. The phenotypic affects of mutations in RUNX2 are potentially protean in consequence. Findings may include moderate short stature, delayed fontanelle closure, parietal, frontal and occipital bossing, open fontanelle in adults, hypertelorism, a low nasal bridge, cleft palate and or a narrow high arched palate with midface hypoplasia or micrognathia. Deafness and various dental abnormalities may also occur. Skeletal findings may include osteosclerosis, increased bone fragility, calvarial thickening, small, hypoplastic or absent clavicles, short ribs, spondylolysis, spondylolisthesis, scoliosis, kyphosis, wide pubic symphysis with delayed mineralization, hypoplastic iliac wing, a broad femoral head with a short neck and coxa vara. The hands may display brachydactyly, a long second metacarpal, short middle phalanges of the second and fifth fingers and abnormal cone shaped phalangeal epiphyses. Syringomyelia has also been observed. Missense, nonsense, splice site, deletion and insertion mutations are the most common mutation types described in RUNX2. Chromosomal translocations and large deletions have been rarely reported.