ESPE Abstracts

Background: Cleidocranial dysplasia (CCD; MIM 119600) is a rare congenital autosomal dominant skeletal dysplasia characterized by hypoplastic or aplastic clavicles, late closure of the fontanelles, open skull sutures, dental anomalies, moderately short stature and a variety of other skeletal features. CCD is caused by mutations, deletions or duplications in the runt-related transcription factor 2 gene (RUNX2), which encodes for a protein essential for osteoblast differentiation and chondocytes maturation.

Case report: We report three familial cases of CCD, misdiagnosed as rickets in three generations. The proband was a 5-year-old girl, who at 3 years of age was diagnosed as having rickets and treated with vitamin D because of large anterior fontanelle and patent skull sutures. At 5 years of age, she was referred to our Pediatric Clinic because persistently open skull sutures and anterior fontanelle associated with frontal and parietal bossing. Physical examination revealed drooping and hypermobile shoulders, which were easily apposed at the midline. Chest X-ray displayed bilateral hypoplastic clavicles. Skull X-ray confirmed a wide open anterior fontanelle, separated sutures, multiple wormian bones, and supernumerary teeth. Family history revealed that her father and her paternal grandmother were treated with vitamin D during childhood, because rickets was diagnosed on the basis of delayed ossification of cranial sutures and fontanelles, as well as pectus excavatum. Chest X-ray of father confirmed bilateral hypoplastic clavicles. No mutations were detected by standard DNA sequencing analysis of RUNX2 gene, but screening for intragenic deletions and duplications by quantitative PCR (qPCR) and multiple ligation-dependent probe amplification (MLPA) revealed a novel deletion of exons 1–3.

Conclusion: Our cases indicate that the diagnosis of CCD could be missed at birth and misdiagnosed as rickets during childhood, leading to inappropriate treatment. Our cases confirm that standard DNA sequencing analysis could not identify mutations in RUNX2 gene in all CCD patients; in these cases screening by qPCR and MLPA can turn out positive results.