An In-Depth Look at Cleidocranial Dysplasia

Cleidocranial dysplasia (CCD) is a rare genetic disorder that affects the development of teeth and bones. It has also been referred to as Scheuthauer-Marie-Santon syndrome, Pierre Marie-Sainton syndrome, and cleidocranial dysostosis. CCD occurs in approximately one in 1 million individuals, with no specific race or gender preference.^1,2

Dental anomalies are very common among individuals with CCD. Oral health professionals should be knowledgeable about CCD characteristics, pathophysiology, treatment, and oral considerations to provide optimal care for people with this condition.

CCD was initially thought to exclusively involve bones of membranous origin such as the face, skull, and clavicle. However, medical discoveries have found CCD is a generalized skeletal dysplasia affecting the entire skeleton rather than just the clavicles and skull. Hence, CCD is considered a dysplasia rather than a dysostosis (disorder of an individual bone).²

Characteristics

Clinical features of CCD are typically discernable in early childhood, and include incompletely formed or missing clavicles, delayed closure of fontanelles (soft spots on infant’s head where cranial bones have not fused together), short stature, pigeon or conical shape of chest, abnormally long neck, and abnormal teeth development.^2–4 An individual with CCD usually has a prominent forehead with a vertical groove down the middle. Narrow and sloping shoulders may also be present.

The anomaly in the clavicle allows for exaggerated shoulder movement.² In some cases, repeated infection of the respiratory tract and ear may be present.³ The nasal bones may be missing or hypoplastic, dense alveolar crestal bone can be present in the mandible, maxillary sinuses can be either unusually small or missing, and the zygomatic arch may be narrow or uneven.² The clinical appearance of CCD varies widely even among people who are genetically related.

Distinct radiographic features of CCD include diminished or missing clavicles in the thoracic area and hindered ossification of skull and pelvic bones. The clavicles are typically hypoplastic or broken, either unilaterally or bilaterally. In 10% of cases, the clavicles are completely absent.^2,5 The presence of Wormian bones (extra bones within the sutures of the skull) may also occur due to abnormal ossification. Brachycephaly, bell-shaped thorax, and pelvic anomalies (such as hypoplastic iliac wings and wide symphysis pubis) can also be found radiographically.⁶ Radiographic evaluation of the patient is important in confirming the diagnosis, which can be made as early as the prenatal period via ultrasound.^3,5

Pathophysiology

This genetic disorder was mapped to chromosome 6p21 by Mundlos et al⁷ in 1995. The gene responsible for this disorder, core-binding factor alpha 1 (CBFA1), now known as runt-related transcription factor 2 (RUNX2), was identified in 1997 by Mundlos et al.⁸ Since then, more than 100 mutations of RUNX2 have been identified and 55 of those are associated with CCD.^9–11 The RUNX2 gene specializes in osteoblastic differentiation (formation and accumulation of bone), chondrocyte (cells responsible for cartilage formation) maturation, and bone formation.^12,13 Mutations in the RUNX2 gene are responsible for two-thirds of CCD cases.^9,14 In one-third of CCD cases, the mutated gene is not found, and the cause is unknown.^2,9,15,16

Maxillofacial Considerations

Common dental anomalies of CCD include multiple supernumerary teeth, a small maxilla with a normal sized mandible that gives an appearance of prognathism, abnormal permanent teeth morphology (especially involving the roots), midface retrusion, and delayed eruption of permanent teeth, usually leading to prolonged retention of primary teeth.^5,17,18 If left untreated, these dental anomalies can lead to crowding, malocclusion, and anterior open bite.³ In a study of patients with CCD, 93.5% displayed dental anomalies, making this a primary feature of the disorder.¹⁹ Additionally, abnormal crown development with hypoplastic enamel and dentigerous cysts/taurodontia have been documented in research.⁴

Studies show that supernumerary teeth appear in 39% to 100% of patients with CCD.^4,6,20,21 Several theories have been suggested to explain the causes of supernumerary teeth such as genetic atavism (reappearance of a trait that has been lost during evolution), separation of a tooth germ, dental lamina hyperactivity, and incomplete or delayed resorption of dental lamina.²² Excess teeth may be normal or developmentally abnormal and located in the front, behind, or within rows of teeth. They may also be arranged as a double row of teeth or located sporadically throughout the jaw.

Several studies have reported the occurence of retained primary teeth and impacted primary teeth in most patients with CCD.^3–6,20 Various factors contribute to these phenomena, including the presence of supernumerary teeth, deformed roots of permanent teeth with a lack of cellular cementum, and abnormal resorption of primary teeth and alveolar bone.²³

Several studies have found class III malocclusion present in patients with CCD, as well as open bites, crossbites, crowding, and high-arched palate.^{3,15,21,24,25} Malocclusion in patients with CCD is generally caused by the development of supernumerary teeth. Due to malocclusion, articulation and mastication may be compromised. The skeletal relationship of the jaws is usually Class III occlusion due to the presence of a hypoplastic maxilla. Malocclusion is not only an esthetic problem but also has negative health effects, including airway obstructions, sleep apnea, immune deficiencies, gastric disturbance, and delayed developmental growth. Oral health professionals should refer patients with malocclusion to an orthodontist for evaluation.^26­–29

Treatment

The course of dental treatment is often determined by the patient’s age at time of diagnosis.³ Combined treatment of surgery and orthodontics is effective for achieving almost complete permanent dentition and occlusal contact.³⁰ Table 1 lists the four most common surgical-orthodontic approaches. The most significant difference between types is when treatment should be initiated.^3,24,31

Interprofessional collaboration is essential to support quality of life in patients with CCD because the disorder impacts the entire skeleton. Primary care providers might recommend a helmet if the cranial vault defect needs extra protection from blunt trauma. If bone density is below normal, calcium and vitamin D supplements may be indicated.³²

To address dental manifestations, orthodontists, oral surgeons, and prosthodontists may be included in treatment planning. Speech therapy may also be recommended due to possible changes in the oral maxillofacial region. Ear, nose, and throat physicians may be needed to treat aggressive and reoccurring sinus and middle ear infections.^3,32 Oral health professionals should collaborate with patients’ other healthcare providers to create a specialized treatment plan that meets their specific oral and systemic health needs in a timely manner.

Patient Management

Several oral hygiene treatment modifications may be necessary for patients with CCD. Oral health professionals should be familiar with the signs of CCD to provide appropriate dental interventions and referrals to specialists as needed. Additionally, clinicians should educate patients on dental anomalies associated with CCD and how to manage them.

The process of care starts with assessing patients as soon as they enter the treatment area. Common physical characteristics are short stature, missing or malformed clavicles, pigeon or conical shape of chest, abnormally long neck, prominent forehead with a vertical groove down the middle, and narrow and sloping shoulders. Patients’ health histories should be reviewed and updated at the beginning of every appointment. Oral health professionals should ask patients if they are currently undergoing treatment with other healthcare professionals.

When conducting an oral examination, the oral hygiene professional should be aware of the manifestations associated with CCD including delayed exfoliation of primary teeth, delayed eruption of permanent teeth, multiple supernumerary teeth, and protruding mandible.¹⁸ Radiographs are necessary to assess the number of supernumerary teeth and whether permanent teeth are present to replace retained primary teeth. All present primary, permanent, and supernumerary teeth should be documented in the patient’s dental chart.

Occlusion must be noted, as malocclusion is a common oral consideration in this patient population. Overcrowding of teeth and malocclusion may create challenges to maintaining adequate oral self-care, thus promoting the formation and retention of plaque and calculus, resulting in gingival inflammation. Not only does malocclusion present oral health implications, it also general health implications, such as sleep apnea, which is associated with significant morbidity.^28,33 Therefore, oral health professionals should screen patients with CCD for malocclusion and refer high-risk individuals to a specialist.

CCD treatment commonly involves surgery-orthodontics, so patients may have orthodontic appliances. Patient education on effective biofilm removal with appropriate oral hygiene aids is essential. Oral health professionals should recommend a power toothbrush for more effective biofilm removal around orthodontic wires and brackets. For interproximal biofilm removal, a floss threader or other specialized floss can be recommended. In addition to flossing, an oral irrigator may be used to achieve optimal oral hygiene especially around crowded teeth, supernumerary teeth, and orthodontia.

Patients with orthodontic appliances are at increased risk of tooth decay so performing a caries risk assessment is key. Over-the-counter fluoride toothpaste, fluoride mouthrinse, and xylitol should be recommended for patients with CCD at moderate caries risk. Those at high caries risk may benefit from prescription-strength fluoride products and antibacterial agents such as chlorhexidine and xylitol. The application of in-office fluoride treatments, such as a varnish, is indicated for patients at moderate and high risk levels.

Patients who have undergone oral surgery will need postoperative instructions about surgical extraction site healing. Aside from the biological factors of tissue healing and regeneration, the patient’s post-operative care of the wound is also essential. Excessive rinsing of the mouth on the day of the operation, tobacco or alcohol consumption, and exerting strenuous physical effort can cause disruption of the tissue coagulation and lead to infection. Patients must be aware that biofilm also impacts healing. Excessive biofilm contamination of the wound can hinder recovery. Educating the patient on minimizing the risk of bacterial contamination by maintaining a good oral hygiene routine at home is essential.³⁴

Conclusion

CCD is a rare genetic disorder that affects the entire skeleton with a variety of characteristics including abnormal development of the dentition. Dental anomalies are a common manifestation and include supernumerary teeth, retention of primary teeth, and malocclusion. Dental professionals should be familiar with the signs and symptoms of CCD, provide referrals to specialists when indicated, and offer appropriate oral health education and interventions.

References

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From Dimensions of Dental Hygiene. Jan/Feb 2024; 22(1):28-31