Discussion Author: Jason W. Schroeder
Cleidocranial Dysostosis/Dysplasia (CCD) is an autosomal dominant disorder, approximately 2/3 of patients have a family history of the disease. It was originally described as a disorder of membraneous bone formation - hence the association of clavicle and skull dysplasia.
â€¢ Autosomal dominant - heterogeneous mutation of RUNX2 gene on chromosome 6p21 - controls precursor cell differentiation into osteoblasts for both enchondral and membranous bone.
â€¢ Skeletal dysplasia involving:
Â» near complete absence of the clavicles (rare total absence); underdevelopment involves acromial end
Â» underossified and thinned calvarium, results in widened calvarial sutures
Â» multiple wormian bones
Â» hypoplasia of the maxilla and facial bones
Â» sclerosis of the skull base and petrous bones
Â» narrowed external auditory canal
Â» small ossicles, stapes footplate fixation
Â» dental anomalies
Â» hypoplasia and underossification of the terminal phalanges
Â» underossification of the pelvis with widened pubic symphysis
â€¢ Normal primary teeth, supernumerary teeth, and failure of secondary (permanent or adult) teeth to erupt is virtually diagnostic of CCD.
â€¢ Short stature
â€¢ Palate abnormalities - including cleft
â€¢ Hearing loss
Cleidocranial dysplasia: clinical and molecular genetics.
J Med Genet. 1999 Mar;36(3):177-82.
Cleidocranial dysplasia (CCD) (MIM 119600) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene has been mapped to chromosome 6p21 within a region containing CBFA1, a member of the runt family of transcription factors. Mutations in the CBFA1 gene that presumably lead to synthesis of an inactive gene product were identified in patients with CCD. The function of CBFA1 during skeletal development was further elucidated by the generation of mutated mice in which the Cbfa1 gene locus was targeted. Loss of one Cbfa1 allele (+/-) leads to a phenotype very similar to human CCD, featuring hypoplasia of the clavicles and patent fontanelles. Loss of both alleles (-/-) leads to a complete absence of bone owing to a lack of osteoblast differentiation. These studies show that haploinsufficiency of CBFA1 causes the CCD phenotype. CBFA1 controls differentiation of precursor cells into osteoblasts and is thus essential for membranous as well as endochondral bone formation.
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