Familial Cleidocranial Dysplasia: A Diagnostic Challenge

Abstract

Cleidocranial dysplasia (CCD) is a rare genetic disorder affecting primarily the cranium, clavicle, and dental tissues. The expression of this disorder can vary widely in severity, even within the same family. Here we present a case report of an affected mother and son with classical manifestations of the disease.

Introduction

Cleidocranial dysplasia (CCD) is a rare genetic disorder inherited in an autosomal dominant pattern. The mutation of the gene RUNX2 found on the short arm of chromosome 6p21 results in the impaired differentiation of stem cells into osteoblasts, interfering with normal bone and cartilage development. This results in the signs and symptoms of cleidocranial dysplasia [1]. Although 40% of the affected cases occur spontaneously with no apparent genetic cause, and one out of three patients have unaffected parents [2].

The clinical feature of CCD patients is the triad of malformations of the body’s hard tissues, especially the cranium, the clavicle and the dental tissues [3]. Clavicular dysplasia is one of the consistent features of the disease [4]. Dental dysplasia occurs in almost all patients, manifested mainly by a delayed eruption or failure of eruption of permanent dentition and the presence of multiple supernumerary teeth [4, 5]. We herein report a case of Familial CCD that was not previously diagnosed because of the extremely low incidence of this disorder.

Case Report

A 13-year-old patient reported to the OPD of Hazaribagh College of dental sciences and Hospital with the chief complaint of retained milk teeth and missing teeth in the upper front teeth region. On further history taking, it was confirmed by the mother of the patient, aged about 40 years that she had a similar condition in the past and had to undergo surgical extraction for multiple retained and unerupted teeth. Upon observation, the facies and the mother and son’s stance were suggestive of the classical manifestations of cleidocranial dysplasia.

A general physical examination revealed a well-oriented young boy with narrow, drooped and hypermobile shoulders. Facial examination showed a brachycephalic head with frontal bossing, depressed metopic suture, hypertelorism, hypoplastic maxillary and zygomatic bones, bulging calvarium, and depressed nasal bridge with a broad alar base (Fig. 1A). Further examination showed an abnormal facility in opposing his shoulders due to malformed or absent clavicles, which was later confirmed with chest radiographs.

Fig. 1.

(A) Physical appearance of the 13 year old, showing brachycephalic head with frontal bossing, depressed metopic suture, hypertelorism, hypoplastic maxillary and zygomatic bones, bulging calvarium, and depressed nasal bridge with a broad alar base. (B) Chest radiograph showing hypoplasia of clavicles on both sides. (C) Panoramic radiograph showing multiple, retained deciduous, impacted and supernumerary teeth

An intra-oral examination revealed a high-arched palate with a rotated maxillary left central incisor, and multiple unerupted permanent and retained deciduous teeth.

An X-ray chest and OPG were advised. The X-ray chest showed clavicles were deficient laterally (Fig. 1B). The OPG showed multiple impacted permanent teeth and multiple retained deciduous teeth and supernumerary teeth (Fig. 1C).

The mother’s physical appearance was similar to the son’s with all the characteristic features (Fig. 2A). The mother had more pronounced brachydactyly than the son (Fig. 2B). The mother had hypodontia and has been using a removable partial denture for the last 15 years.

Fig. 2.

(A) physical appearance of the 40 years old mother. (B) More pronounced brachydactyly. (C) Panoramic view of the mother showing multiple missing teeth, impacted teeth and placement of miniplates in the body of the mandible bilaterally

An OPG was also requested of the mother and it showed multiple missing teeth, impacted teeth and placement of miniplates in the body of the mandible bilaterally (Fig. 2C). The diagnosis of cleidocranial dysplasia was confirmed radiographically further by obtaining an X-ray skull and an X-ray hand-wrist.

The treatment plan was made to obtain substantial aesthetic and functional benefits. The patient was referred to the departments of Oral Surgery and Orthodontics. Extraction of the retained deciduous and supernumerary teeth followed by Orthodontic treatment with mini-implant screws for traction of impacted teeth was planned. The patient was also advised to visit a higher medical canter for his concern regarding calvarial defects in the open anterior fontanelle and metopic sutures.

Discussion

Cleidocranial dysplasia (CCD) was first described by Pierre Marie and Paul Sainton in 1898 [6]. CCD is a congenial, developmental disorder that primarily affects calvarial bones, clavicles and teeth [7]. The incidence of CCD is reported to be about 1/1,000,000 without any gender or racial difference. The low incidence of CCD may be due to lack of medical access in rural periphery of developing countries or its clinical features can be mistaken for a number of other conditions like Noonan syndrome, Turner’s syndrome, hypothyroidism and other skeletal dysplasia, before being diagnosed radiologically [8]. The phenotypic spectrum of CCD ranges from mild to severely affected patients [2].

The aetiology and pathogenesis of the syndrome remained unknown for many decades. Later, genetic studies revealed that sixteen different types of mutation of the Cbfa1 (RUNX2) gene on the short arm of chromosome 6p21 is responsible for this syndrome [9]. The Cbfa1 (RUNX2) gene controls normal growth and development of the human skeleton through intramembranous and endochondral ossification [10]. It also regulates the gene expression of dental epithelium mesenchymal cells, and in this manner, the deficiency of transcription factor Cbfa1 leads to the manifestation of the skeletal and dental anomalies observed in patients with CCD [11].

The clinical features of CCD are recognized during early childhood and include short stature, delayed closure of fontanelles, prominent forehead, and abnormal dental development. Aplastic or hypoplastic clavicles, hypermobility of scapula, brachycephaly, hypertelorism, frontal and biparietal bossing, Midface deficiency, underdeveloped paranasal sinuses, hypoplastic maxillary, nasal, and zygomatic bones; flattened nasal bridge; a wide alar base; and prominent frontal, parietal, and occipital bones [1]. Other features seen in CCD are deformities of the thoracic region, pelvic and pubic bones, and fingers [5].

The common dental disturbances include pseudo-mandibular prognathism due to midface deficiency, supernumerary teeth, prolonged retention of the primary dentition, failed eruption of the permanent teeth, cyst formation around impacted teeth, and ectopic eruption of teeth. A highly arched palate is a less common oral manifestation of CCD [12].

Management of dental and orofacial manifestations of CCD is a challenging long-term process requiring proper planning and execution. Dental management of cleidocranial dysplasia is largely dependent on the chronological and dental age of the patients. Treatment includes removal of the impacted permanent, supernumerary and primary teeth, combined with fabrication of over-dentures; surgical removal of the primary and supernumerary teeth, combined with orthodontic traction of the impacted permanent teeth; removal of the supernumerary teeth immediately after completion of mineralization of their crowns, combined with removal of the overlying bone of the permanent teeth to facilitate their eruption [13].

Conclusion

The knowledge of typical clinical and radiological features of CCD enables a clinician in achieving early diagnosis and implementation of appropriate treatment to improve the functional and aesthetic appearance of the patient. In our case, in spite of having all the clinical features both the mother and the son remained undiagnosed for a long. This led to more advanced dental malocclusion, which could have been corrected if it was diagnosed in early childhood.

Authors’ contributions

Sugandha Verma, K Srikrishna and Vikas Kumar were involved in dental and medical treatment, data collection, interpretation of the radiological findings and drafting of the manuscript. Sugandha Verma and Vikas Kumar were involved in editing and revising the manuscript. All the authors read and approved the final version of the manuscript.

Declarations

Consent

Written informed consent was obtained from the patient’s mother for the publication of this case report.

Competing Interests

The authors declare that they have no competing interests.