Cleidocranial dysplasia: Clinical, endocrinologic and molecular findings in 15 patients from 11 families
Introduction
Cleidocranial dysplasia (CCD; MIM119600) is a dominantly inherited autosomal disorder characterized by abnormally large fontanels, delayed closure of the cranial sutures, frontal bossing, mid-face retrusion, various dental abnormalities, narrow sloping shoulders due to underdeveloped or absent clavicles, and other skeletal abnormalities (Mundlos et al., 1997). Affected individuals are shorter than their unaffected siblings (Cooper et al., 2001). The related dental abnormalities include retained deciduous teeth, supernumerary teeth, delayed eruption of permanent teeth and malocclusion (Roberts et al., 2013). Mutations of RUNX2, encoding an essential transcription factor for differentiation of osteoblasts, maturation of chondrocytes, and regulation of bone metabolism, are found in 70% of the cases, consisting of pathogenic sequence variants in proportions of 60% and gross deletions in the remaining 10% (Komori, 2007, Ott et al., 2010, Zanatta et al., 2012). To date, 194 mutations are associated within a considerably wide phenotypic spectrum of CCD, encompassing inter- and intra-familial variability ranging from a single clinical finding of primary dental anomalies to full-blown CCD phenotype including serious osteopenia with multiple fractures (https://portal.biobase-international.com; Lee et al., 2013, Ramesar et al., 1996, Zhou et al., 1999).
In this study, we report clinical, endocrinologic and molecular findings of 15 patients with CCD from 11 different families from Turkey.
Section snippets
Patients
The patients underwent detailed clinical evaluation, which included general and craniofacial examination, oral/dental evaluation, skeletal survey, radiological images and endocrinologic laboratory tests. Registration of detailed medical history was followed by a physical examination, that included measurements of height and weight according to standard methods. Values of height, weight and body mass index (BMI) were expressed as Standard Deviation Score (SDS) according to Turkish standards (
Clinical findings
The patient group was comprised of seven females and eight males from 11 independent families (Fig. 1). Seven patients were sporadic (F1, F2, F5, F6, F7, F9, F10), seven were familial form from three different families (F3, F4, F8), while one subject was an abandoned child from orphanage cared by a foster family (F11). Clinical findings are summarized in Table 1. The patients’ photographs and radiological findings are presented in Suppl. Fig. 1 and Suppl. Fig. 2.
Coincidental clinical findings
Discussion
All of the affected individuals in this study were diagnosed with classical clinical and radiographical findings of CCD. Our molecular investigation delineated the genetic basis in ∼90% of the cases. The small size of our cohort most likely could explain our mutation frequency findings to be much greater than larger group studies, which have generally reported this ratio to be ∼70%.
Two mutations, p. R225Q and p. R391*, appear to be recurrent in our group, since both were identified in two
Conflict of interest
All authors declare no conflict of interest.
Acknowledgements
We sincerely thank the patients and their families for their contribution to this study, which was supported by the Scientific and Technological Research Institution of Turkey, TUBİTAK-ERA NET (CRANIRARE-2, grant number: SBAG-112S398).
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