The Orthodontic CYBERjournal, March 2010

Cleidocranial Dysplasia (Dysostosis) A Case Report

Dr. Satheesh Kumar Reddy , MDS Professor, Department of orthodontics & Dentofacial Orthopaedics, Sri Sai College of Dental surgery and Research, Vikarabad. Member Dental council of India Corresponding author - [email protected]

Co-Author Dr. Renu Parmar PG Final Year, Department of orthodontics & Dentofacial Orthopaedics , Sri Sai College of Dental surgery and Research, Vikarabad

Abstract: Cleidocranial dysplasia (CCD) is an autosomal dominant disease with complete penetrance, but variable expressivity, first described by Marie and Sainton in 1898. The phenotype is characterized by general dysplastic bone formation manifested in typical anomalies in the skull: frontal bossing and a prognathic mandible, the pelvis and the thoracic region, hands and feet. Because of delayed skeletal development, commonly CCD patients are of short stature. Characteristic disorders in the primary and secondary dentition are frequently reported. This paper presents a case of cleidocranial dysplsia with its 3D images and rendering.

Introduction Cleidocranial Dysplasia (CCD) is a rare congenital disorder of bone with an autosomal dominant hereditary mode of inheritance. with complete penetrance, but variable expressivity. This condition is characterized by clavicular aplasia or deficient formation of

the clavicles, delayed and imperfect ossification of the cranium, moderately short stature, and a variety of other skeletal abnormalities. The principal oral manifestations are a delayed exfoliation of primary teeth, delayed or multiple impactions of the permanent dentition, and multiple impacted supernumerary teeth. 1

The first case of clavicular defects was reported by Martin in 1765. Another case with both clavicles and the skull affected was reported in 1871 by Scheuthauer. In 1897 Marie and Sainton coined the descriptive term cleidocranial dysostosis. The condition was originally thought to involve bones of intramembranous origin only, namely the bones of the skull, clavicles and flat bones, hence the name cleidocranial. Hesse was first to describe in detail the defects of dentition and jaws associated with cleidocranial dysostosis.

The gene for cleidocranial dysplasia has been mapped on the short arm of chromosome 6p21, core binding factor a-1 (CBFA1). This disorder can be caused by a mutation in the transcription factor CBFA1 (RUNX2) (Fig. 1). The CBFA1 gene controls differentiation of precursor cells into osteoblasts and is, therefore, essential for membranous as well as endochondral bone formation, which may be related to delayed ossification of the skull, teeth, pelvis, and clavicles. The prevalence of cleidocranial dysplasia is one per million with complete penetrance and variable expressivity, but it is most likely under diagnosed because of the relative lack of medical complications in comparison with other skeletal dysplasias. It may be discovered at any age, but the cranial deficiencies may be noticed at birth. Both sexes are affected to an approximately equal extent. The defect often appears in several successive generations. 2

The most characteristic and pathognomonic feature of this disorder is hypoplasia or aplasia of the clavicles, which results in hypermobility of the shoulders allowing the patients to approximate the shoulders in the midline (Fig 2).

Muscle attachments to the clavicles may also be dysplastic, leading to distortion of the neck. Defects of the cervical and lumbar vertebrae are included in the clinical findings. Absence of the pubic symphysis and hypoplasia of the pelvis is common in females. Frequently, genua valga and pes planus are found in children younger than 5 years of age. Moderately short stature was observed. Delayed ossification of the cranial sutures and fontanels occurs, and may remain open throughout life. The skull is usually large and broad, a brachycephalic type.

The face appears small in relation to the cranium with hypoplastic maxillary, lachrymal, nasal, and zygomatic bones. The paranasal sinuses may be underdeveloped. The bones of the middle part of the face are less well developed than the cranial bones. Defects in the skull appear to be always symmetrical. The frontal, parietal, and occipital bones are prominent.

The maxillary sinuses may be small or missing, and the maxilla is underdeveloped, causing a Class III skeletal relationship and a maxillary retrusion (a relative mandibular prognathism). The palate may be abnormally high, and, occasionally, a cleft palate has been reported. Ocular hypertelorism and mild exophthalmus are seen. Postural defects and spinal curvature are common. In the hands and the feet, various abnormalities have been found, the most constant and curious being the presence of epiphyses at both ends of the metacarpals and metatarsals, particularly of the second and fifth, and an abnormally long second metacarpal. The intermediate phalanges may be small. Ossification of the carpus may be delayed. Association with mental retardation has been shown, but most patients apparently possess normal intelligence. These individuals have no significant physical handicap. The eruption of primary teeth is normal or sometimes delayed, but the exfoliation of primary teeth is always delayed and may be due to the failure of most permanent teeth to erupt.

The presence of supernumerary teeth has been hypothesized to result from incomplete or delayed resorption of the dental lamina. Dental manifestations include delayed eruption or failure of eruption of the primary dentition (Table 1). Delayed tooth development has been reported in association with malocclusion and supernumerary teeth. The significant variability in clinical expression of this syndrome reflects a degree of phenotypic polymorphism. 3

Confirmation of the diagnosis routinely includes (a) Clinical examination of the cranium, the face, and the clavicles, including shoulder mobility, (b) Oral examination to compare the eruption status of the dentition and the patient's chronological age,

Table 1. Clinical Findings in Cleidocranial Dysplasias

Hypoplasia clavicles Brachycephalic skull Delayed closure of fontanels

Aplasia clavicles Midface hypoplasia Thickness of the calvaria of the skull

Short stature Genua valga Scoliosis Asthma Delayed exfoliation of primary teeth

Arms and legs small Pes planus Osteoporosis Hearing loss Delayed eruption of permanent teeth

Supernumerary teeth Maxillary hypoplasia High palate Class II malocclusion Alteration of dental hard tissue

Mandibular prognathism Dentigerous cysts Cleft palate Class III malocclusion

(c) Radiographic examination-a critical confirmatory diagnostic tool that includes a chest Xray and anteroposterior and lateral skull cephalometric radiographs. A panoramic radiograph with supplementary periapical and occlusal views is needed to determine number, size, and position of supernumerary teeth. With the advent of CT the localization and strategic planning of the impacted teeth has become even more predictable. The patients treatment, which, in this approach, is dependent on the services of an integrated team, made up of a pedodontist, an orthodontist, and an oral and maxillofacial surgeon. 3

(Fig . 1) CBFA1 on chromosome 6p21

(Fig 2) Hypermobility of shoulders & Clavicular hypoplasia Case Report This article presents a case of CCD where the patient, aged 13 yrs/ F reported to the Pacific dental clinic with the chief complaint of multiple missing teeth. The patients younger sister also had similar dental problems and both of the siblings were diagnosed with CCD. Multiple, over-retained deciduous teeth were present and the OPG showed multiple impacted permanent teeth and a few supernumerary teeth. Since the localization of the impacted teeth was difficult, a 2D OPG (Fig. 3), a 3D CT imaging was proposed and a 3D rendering was also performed. (Fig 4) This case report supports the appropriate use of 3D imaging in those cases of cranio-facial deformities and multiple impacted teeth, in order to better comprehend the depth of the problem and for patient education. However, before a 3D imaging procedure is opted for, the cost/benefit and the risk of excessive radiation to the benefits achieved should be assessed.

(Fig.3) 2D showing multiple impacted teeth

(Fig 4) The 3D rendering

(Fig. 5) The various views obtained from a single CT exposure

(Cont. Fig 5.)

The various CT images not only help in strategic planning of the various impacted teeth but also, aids in visualizing the entire region of interest in whatever angle is desired. It also helps to educate the patient, thereby enhancing their support in the treatment.

DISCUSSION

This case discusses several characteristic anomalies in a patient with cleidocranial dysplasia. Orthodontic treatment is usually indicated to direct the eruption of the malposed and often impacted teeth. Extraction of some of the supernumerary teeth may be needed. Timing of the intervention is critical, and many surgeries may be required. Patients with cleidocranial dysplasia require a team approach involving an orthodontist, pedodontist and an oral surgeon with good cooperation and communication from the patient.

Acknowledgement - The authors thank Pacific private dental hospital and Pvt. Lmt. for their valuable support for providing the patients CT images.

References -

1. I. Golan, U. Baumert, D. Mu ig, H. Wagener, H. Niederdellmann, J. Dauwerse, M. Preising, B. Lorenz. Atypical expression of cleidocranial dysplasia: clinical and molecular-genetic analysis. Orthod. Craniofacial Res. 5, 2002; 243249

2. Roberto Mendoza, Brendan Lee. Gene review, google.com

3. Giampietro Farronato; Cinzia Maspero; Davide Farronato; Silvia Gioventu`. Orthodontic Treatment in a Patient with Cleidocranial Dysostosis. Angle Orthod. 2009;79:178185.

4. Adrian Becker, Arye Shteyer, Enrique Bimstein, and Joshua Lustmann. Cleidocranial dysplasia: Part 2Treatment protocol for the orthodontic and surgical modality. AJODO Volume 1997 Feb: 173 183.

5. Schroeder TM, Jensen ED, Westendorf JJ. Birth Defects Res C Embryo Today. 2005 Sep;75(3):213-25. Runx2: a master organizer of gene transcription in developing and maturing osteoblasts.

Dr. Satheesh Kumar Reddy , MDS