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At a glance

A nonneoplastic, fibroosseous disease characterized by bilateral, and painless enlargement of the jaws that give the patient a cherubic appearance.

Synonyms

Familial Benign Giant Cell Tumor of the Jaw; Familial Multilocular Cystic Disease of the Jaw.

History

First described by Frangenheim in 1914 and completed by the Canadian physician William A. Jones in 1933.

Incidence

A Norwegian study estimated the prevalence to be in the range of 1:180,000. Approximately 300 cases have been reported in the literature.

Genetic inheritance

Autosomal dominant trait, with males and females being equally affected. Penetrance in males has been reported as 100% versus only 50 to 70% in females; however, many experts now consider this data historical and more recent research considers equal penetrance rates for males and females. It may appear as a solitary case or in several members of a family, often affecting multiple generations. Sporadic cases have also been described. In approximately 80% of patients, the disorder is caused by heterozygous missense mutations in the SH3BP2 (SH3-binding protein 2) gene, which has been mapped to chromosome 4p16.3. The SH3 region is a small protein domain that includes signaling proteins and cytoskeletal elements and appears to function as mediators in protein-protein associations and regulation of cytoplasmic signaling. It further is important in the binding of tankyrase, which regulates the ubiquitination of SH3BP2 (ie, its binding to ubiquitin) and leads to tumor necrosis factor alpha-induced inflammation with subsequent bone loss. The mutations in Cherubism continuously increase the biological activity of SH3BP2. No correlation could be detected between the cherubism genotype and the clinical phenotype.

Pathophysiology

Unknown. It may be related to dental developmental processes in children, triggered by the eruption of secondary teeth.

Diagnosis

Made based on the family history and the clinical findings of characteristic “cherub-like” facies caused most often by symmetrical fullness of the cheeks and jaws, resulting in a round face. Radiologic examination shows multilocular cystic changes in mandible and maxilla. Histologic examination of affected areas reveals replacement of the normal bony architecture by proliferating cellular fibrous tissues, containing numerous, multinucleated giant cells. The clinical phenotype is highly variable ranging from almost asymptomatic bilateral mandibular and/or maxillary swellings to massive and life-threatening space-occupying lesions with significant bone destructions. Occasionally, mutation analysis of SH3BP2 can be helpful.

Clinical aspects

These patients may look normal in the first year of life. The initial changes are characterized by unilateral fullness of the cheeks, most often starting between the second and fifth year of life (but later onset is possible). Eventually, both mandibular rami and angles are involved, along with the maxilla. Most often, the disease involves both, maxilla and mandible. Retraction of the lower eyelids ...

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