Cherubism: Clinical features
- Cherubism is an autosomal-dominant genetic defect that affects bone remodeling in the specific anatomically confined limits of the embryologic mandible and sometimes of the mandible and maxilla.
- Cherubism does not occur in any other bone and will not cross a bony suture to an adjacent bone.
- Cherubism first begins to manifest itself by the age of 2.5 years and is fully expressed by the age of 5 years.
- It affects males slightly more than females because of a 100% genetic penetrance in males and only a 50% to 70% genetic penetrance in females.
- Its relatively rapid progression and is often associated with regional lymphadenopathy and, if the maxilla is involved, nasal obstruction with resultant mouth breathing.
- Nasal obstruction is caused by enlargement of the middle concha. Because the genetic defect is expressed on the embryologic maxilla or mandible only, the other conchae-the inferior concha, which is an independent bone, and the superior concha, which is part of the ethmoid bone-are not involved.
- Spontaneous mutations, called sporadic occurrences, are more common in cherubism than in most other inherited diseases and account for up to 40% of cases.
Types of Cherubism:
Cherubism has three levels of expression.
- Type I forms only in the bilateral rami of the mandible, sparing the condyle and extending only to the third molar region. This form may be so subtle that it escapes clinical detection until radiographs are taken years later. It is probable that most of the reported cases of so-called bilateral giant cell lesions of the mandible actually represent this type of cherubism, often called a forme fruste or incomplete expression of the disease.
- Type II forms mostly in the mandible and also spares the condyle, but it extends to at least the mental foramen bilaterally and may include the posterior maxilla.
- Type III is the form that prompted the name cherubism. This form involves the mandible bilaterally to an advanced degree as compared to type II and also includes most, if not all, of the maxilla. The involvement of the maxilla’s contribution to the orbital floor and orbital rim displaces the globes upward, causing a scleral show. This feature, combined with the expansion of the maxilla, gives a child with cherubism the chubby-faced appearance and the “upward-to-heaven”-looking eyes of a cherub. The maxillary involvement includes the alveolar bone and palate but does not extend beyond the maxillary sutures. Therefore, the adjacent palatine bones, vomer, zygomas, and nasal bones are completely normal.
- The child will therefore present with some degree of expanded facies and the possibility of nasal obstruction, lymphadenopathy, dry mouth, drooling, and, rarely, pain. Clinically, there may be missing teeth, multiple diastemas, and misplaced teeth.
Radiographically, the involved bones show a dramatic, multilocular radiolucency with thin and expanded cortices, including the inferior border. The condyle and condylar neck appear normal. Unerupted and displaced teeth are common. Radiographically and clinically, cases show symmetric involvement. Cases that do not show symmetry (ie, unilateral involvement) may not be true cherubism but similar giant cell lesions that are variable components of other diseases such as Noonan syndrome or Jaffe-Campanacci syndrome.
Cherubism, like most fibro-osseous diseases, requires a clinical and radiographic diagnosis rather than a histopathologic diagnosis. It must therefore be distinguished from other bilateral, multilocular, radiolucent lesions of the jaws in young children. Other entities that may mimic this presentation are primary hyperparathyroidism, Langerhans cell histiocytosis, and multiple odontogenic keratocysts, perhaps as part of the basal cell nevus syndrome. In addition, Noonan syndrome and Jaffe-Campanacci syndrome may be considered, particularly if a fibrovascular giant cell lesion is confirmed by a biopsy.
The specific clinical and radiographic features that permit a diagnosis of cherubism are symmetric presentation, radiographic evidence of multilocular contiguous lesions, sparing of the condyle, lack of involvement of adjacent bones, middle concha enlargement (variable) in the maxilla, and emergence and expression of the disease between the ages of 2 and 5 years.
The lesions of cherubism consist of a vascular fibrous stroma, extravasated erythrocytes, and scattered multinucleated giant cells. An increase in the amount of fibrous tissue and a corresponding decrease in the number of giant cells is probably associated with regressing lesions. An eosinophilic perivascular cuffing of collagen is considered characteristic of cherubism; however, this feature is frequently absent. Clinical and radiographic correlation is necessary because the histologic features strongly resemble those seen in central giant cell tumors and the lesions of hyperparathyroidism.
Treatment and prognosis
As with any genetic disease, cherubism currently is not curable. However, the natural course of cherubism is one of gradual enlargement that continues until the onset of puberty. After puberty, a gradual involution begins and is often complete by age 18 to 20 years, almost never lasting beyond age 30 years. The result is a nearly complete reversal of the facial expansion, which is usually very well accepted by the individual. Radiographs show only partial bony regeneration as residual radiolucent areas persist. There also may be unerupted and displaced teeth. This eruption disturbance, which occurs throughout the childhood years, may cause the patient to be partially edentulous.
The general clinical approach is to avoid surgery altogether and allow natural involution to take place or defer surgeries until after puberty. If reduction of the expanded bone (osseous contouring) is required before the late teenage years because of pain or psychologic needs, it is done with the knowledge that the operated bone will re-expand at the same or a higher rate of expansion as before surgery. Resection of cherubic bone is discouraged. While type III cherubism may present similar to a large benign tumor, the natural course of the disease produces a gradual cessation of expansion and a regression. Such ill-advised resections have only resulted in an unnecessary deformity and the need for extensive reconstructive surgeries. There is some concern that osseous contouring may accelerate the rate of expansion, but the limited experience with surgery on these patients does not support this concern. There is also no evidence that surgical intervention will stimulate malignant transformation. If osseous contouring is required, mostly in individuals over 18 years in whom persistent expansion has occurred or in a young patient, the surgeon must be aware of the vascular nature of the bone and proceed with the same intraoperative hemorrhage control procedures as would be used in treating a central giant cell tumor (ie, an elevated head position, hypotensive anesthesia, an accessible supply of hemostatic packs, and a preparation of autologous blood or “designated donor” blood available for transfusion). In addition, the surgeon must anticipate that a significant amount of cherubic tissue must be removed to gain the desired contour reduction.
On occasion, the nasal obstruction can become severe, leading to airway concerns or to significant mouth breathing and an open-bite deformity. In such cases, removal of the middle concha and turbinates is a reasonable and beneficial procedure.