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Journal of Indian Society of Pedodontics and Preventive Dentistry Official publication of Indian Society of Pedodontics and Preventive Dentistry
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CASE REPORT
Year : 2009  |  Volume : 27  |  Issue : 4  |  Page : 249-252
 

Cleidocranial dysplasia: A family report


1 Departments of Oral Pathology, and Orthodontia, Sri Ramachandra DentalCollege, Porur, Chennai, India
2 Department of Paedodontia, Sri Ramachandra DentalCollege, Porur, Chennai, India

Date of Web Publication14-Nov-2009

Correspondence Address:
H Thamizh Chelvan
Department of Oral Pathology, Sri Ramachandra Dental College and Hospital, Sri Ramachandra University, Porur, Chennai - 600 116
India
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DOI: 10.4103/0970-4388.57661

PMID: 19915277

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   Abstract 

A 10-year-old girl presented with a chief complaint of many unerupted teeth. Complete clinical and radiological examination of this patient confirmed the diagnosis of cleidocranial dysplasia (CCD). Her father also presented similar features with a lesser clinical severity. CCD is an autosomal-dominant heritable skeletal disease caused by heterozygous mutations in the osteoblast-specific transcription factor RUNX2 gene. Failure of tooth eruption is probably mainly due to this mutated gene in CCD patients. Interdisciplinary treatment approach is obligatory for rehabilitation of these patients. In confirmed cases, genetic counseling for family planning should certainly be advised.


Keywords: Cleidocranial dysplasia, RUNX, dysplasia


How to cite this article:
Chelvan H T, Malathi N, Kailasam V, Ponnudurai A. Cleidocranial dysplasia: A family report. J Indian Soc Pedod Prev Dent 2009;27:249-52

How to cite this URL:
Chelvan H T, Malathi N, Kailasam V, Ponnudurai A. Cleidocranial dysplasia: A family report. J Indian Soc Pedod Prev Dent [serial online] 2009 [cited 2014 Jul 26];27:249-52. Available from: http://www.jisppd.com/text.asp?2009/27/4/249/57661



   Introduction Top


Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal bone disease affecting the skeletal and dental system, primarily involving bones formed by intramembranous ossification, such as facial bones, cranium and clavicles. The disease is characterized by persistently open or delayed closure of sutures, hypoplastic or aplastic clavicles and short stature. Multiple supernumerary teeth are present often accompanied by delayed or disturbed eruption of permanent teeth. The vertebral column and appendicular skeleton are also affected, indicating endochondral ossification. [1],[2] CCD is a rare disease with a prevalence of less than 1 per million. [3]

Recently, human osteoblast-specific, runt-related transcription factor 2 (RUNX2) gene, previously called as PEBP2Ͳa, CBFA1 (core binding factor A1), AML3 or OSF2 is identified as the gene responsible for CCD. The gene is mapped to chromosome 6p21, where the transcriptional factor CBFA1 is located. RUNX family consists of three members - RUNX1 for definitive hematopoiesis, RUNX2 called as "master gene" of bone development and needed for ostoeoblast differention and RUNX3, which cooperates with RUNX2 in promoting chondrocyte maturation. [1],[3]

In general, CCD patients are of a normal intelligence quotient and health. They are slightly dwarfed and slender and have long necks and drooped shoulders. The most striking feature of this condition is the appearance of the brachiocephalic head and facies. In many occasions, the anterior fontanelle may remain open into adulthood. The orbital ridges are prominent but the inferior margins are shrunken into small maxillae, which gives the face a flattened appearance-midface hypoplasia and a relative mandibular prognatism. The other clinical features are biparietal cranial enlargement, hypertelorism, prominent chin, high-arched palate and absence of the nasal bone in few cases. A major indicator of CCD includes hypoplasia or aplasia of clavicular bones resulting in the ability of the patient to approximate the shoulders. The clavicular defects are frequently associated with drooping ribs. [1],[2]

Narrow and abnormally shaped pelvic and pubic bones as well as deformities in the thoracic region are other features seen in CCD. The other associated defects are abnormalities in spine, hand and feet. Hand abnormalities include short, tapered fingers and thumb with shortening of distal phalanges. Clinodactyly of the fifth finger may be present as well. Scoliosis may develop in many patients and syringomyelia has been reported. [1],[2]

A myriad of irregularities in dentition exists, including delayed or non-eruption of deciduous and permanent teeth that may or may not be associated with the presence of multiple supernumerary teeth. [4] Oral X-ray findings mentioned by few studies include a parallel-sided ascending ramus, a distally curved coronoid process and a hypoplastic/discontinuous zygomatic bone. [3] Earlier microscopic studies on unerupted teeth in CCD patients exhibited almost complete absence of cellular cementum. [5]


   Case Reports Top


We shall discuss about CCD that occurred in a family where the daughter and father were affected with varying clinical features.

Case 1

The patient was a 10-year-old female referred to the paedodontia department with the chief complaint of many unerupted teeth. On general examination, she was well-oriented, normally built and of short stature. Her physical examination showed short and stout fingers along with hypoplastic nails. Facial examination revealed brachycephalic head along with asymmetry of face. Other orofacial features are fronto-parietal bossing, prominent orbital ridges, mild hypertelorism and depressed nasal bridge along with broad ala-base [Figure 1]. She also exhibited hypermobility of shoulders [Figure 2], a characteristic sign of CCD due to absence or hypoplasia of clavicles, which was further confirmed by chest X-ray that also showed a narrow thorax with drooping ribs [Figure 3]. Intraoral examination showed retention of many deciduous teeth and absence of the right upper permanent central incisor and both lower permanent central incisors. Further examination showed mild bilateral cross-bite and class III incisor relationship. Panoromic examination revealed presence of retained deciduous dentition along with many unerupted permanent teeth and many impacted supernumerary teeth [Figure 4]. One of her exfoliated deciduous molar was subjected to ground examination, which showed absence of cellular cementum [Figure 5].

Case 2

This case was the father of case 1. He was moderately built with a short stature. Clinical involvement of this case is of less severity compared with case1. Frontal bossing [Figure 1] and hypermobility of the shoulders were noted [Figure 2]. Panoramic X-ray showed absence of many permanent teeth along with impacted permanent teeth [Figure 4].

Based on clinical findings, both of these patients were diagnosed as CCD. Complete dental treatment regime was explained and the patients never turned up for further treatment and follow-up.


   Discussion Top


With the development of multiple supernumerary teeth, limited eruption force, impaction of permanent teeth, multiple follicular cysts and altered jaw development, early diagnosis is required for appropriate treatment regimen. In addition, with the identification of the responsible gene, molecular-genetic analysis has become an indispensable diagnostic tool for early detection in cases where CCD is suspected.

The clinical variability ranges from nearly unrecognizable to full-blown cases. The most striking CCD marker, the abnormal shoulder mobility, which was seen in our cases, is not expressed in few cases. The fact that CCD can also affect patients with no supernumerary teeth, or even missing teeth, with over 100 syndromes and developmental conditions having been found to be associated with supernumerary teeth, potentially adding to confusion in the diagnosis of CCD. [4]

It has been proposed that supernumerary teeth in patients with CCD should be diagnosed and removed as early as possible because the supernumerary teeth will always impede normal eruption of permanent teeth. [4]

Indeed, many authors have reported bone abnormalities in the maxillofacial region with which those seen in our cases were consistent. Furuuchi et al., in their study, found that CCD patients had less thick masseter muscles than in the age- and sex-matched control subjects. They concluded that the discontinuity of the zygomatic arch is the likely cause of the hypofunction and reduced thickness of the masseter muscle in CCD patients. On the other hand, CCD is a skeletal dysplasia and the muscle changes may be a secondary effect. [3]

The RUNX family is characterized by a highly conserved 128-amino acid region, as termed after the Drosoplhilia runt gene, one of the founding members to be identified. RUNX2 gene is necessary for tooth development. The deletion of its function in knockout mice arrests tooth development at the bud stage. This gene is one of the key mesenchymal factors that influences tooth morphogenesis and subsequent differentiation of ameloblasts and odontoblasts. [6]

Of those who had previously examined unerupted teeth, the consensus was that there was an anomaly of the cementum and it was thought that this absence of cellular cementum was responsible for the failure of eruption of a significant amount of impacted teeth in patients with CCD. Our case 1 also coincides with this. However, a recent study does not agree with this concept stating that cellular cementum does not have any role. [5] But, after the discovery of RUNX2, it is very clear that failure of eruption is mainly due to mutated RUNX2 gene in these patients. CCD phenotype also includes the third dentition. This indicates, remarkably, that all humans have the potential to develop a third dentition and this is normally inhibited by the RUNX2 genes. [6]

According to Yoshida et al. CCD could result from a much smaller loss in the RUNX2 function. They also implied that an inherent mechanistic commonality exists between the skeletal growth and the dental development in their dependencies on the RUNX2 activity, despite the tremendous apparent dissimilarities of these two organogenesis processes. If the type of mutation in RUNX2 is known in advance, we could predict the supernumerary teeth for an individual to allow the early initiation of the necessary treatment. [7]

The signs and symptoms described here should serve as early markers to aid the general and pediatric dentist in planning appropriate treatment or referring patients to specialized centers. An interdisciplinary treatment approach involving orthodontics, maxillofacial surgery and prosthodontics is obligatory. In confirmed cases, genetic counseling for family planning should certainly be advised. [1]

 
   References Top

1.Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, et al. Functional analysis of Runx2 mutations in Cleidocranial dysplasia: novel insights into genotype-phenotype correlations. Blood Cells Mol Dis 2003:30;184-93.  Back to cited text no. 1      
2.Lowell's and winters -Pediatric orthopaedia. IV edition 1996.  Back to cited text no. 2      
3.Furuuchi T, Kochi S, Sasano T, Iikubo M, Komai S, Igari K. Morphologic characteristics of masseter muscle in cleidocranial dysplasia: A report of three cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:185-90.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Golan I, Baumert U, Hrala BP, Mόssig D. Early craniofacial signs of cleidocranial dysplasia. Int J Paediatr Dent 2004;14;49-53.  Back to cited text no. 4      
5.Counts AL, Rohrer MD, Prasad H, Bolen P. An assessment of root cementum in cleidocranial dysplasia. Angle Orthod 2001;71;293-8.  Back to cited text no. 5      
6.Thesleff I. Developmental biology and building a tooth. Quintessence Int 2003;34;613-20.  Back to cited text no. 6      
7.Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, et al. Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Am J Hum Genet 2002;71:724-38  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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