Clinical Description
Cherubism is a childhood-onset bone disease characterized by bilateral proliferative lesions typically limited to the mandible and maxilla. Regression of the lesions occurs during the second and third decade of life. Findings associated with cherubism range from clinically unrecognized features to severe mandibular and maxillary overgrowth with dental, orbital/ophthalmologic, respiratory, speech, and swallowing complications [Roginsky et al 2009, Kueper et al 2022]. There is wide phenotypic variability even among individuals from the same family [Stoor et al 2017].
Onset and course. Individuals with cherubism have a normal appearance at birth. Usually, cherubism manifests in early childhood (age 2-7 years) and progresses until puberty, when it begins to stabilize and starts to regress. Submandibular and cervical lymph nodes are enlarged during the early stages of cherubism and may present before the recognition of bony lesions. By age 30 years, the facial abnormalities associated with cherubism are not usually recognizable and significant residual deformity of the jaws is rare; however, persisting bone abnormalities are often seen in adults with cherubism [Von Wowern 2000, Redfors et al 2013].
Bone lesions. The disease starts with progressive bone degradation, with rapid evolution in individuals with severe disease. Disease is usually restricted to the mandibular and maxillary regions and leads to multiple bilateral, symmetric cystic changes. Bone lesions develop preferentially at the mandibular level before affecting the maxilla [Roginsky et al 2009].
Severe malformation of the jaw may impede chewing and swallowing. An ache in the mouth and discomfort when eating food are frequently reported [Prescott et al 2013]. Massive enlargement of the jaw is common and can also be associated with severe pain in severe forms; however, bony lesions are usually painless in cherubism. Recurrence of jaw lesions is possible after surgery.
The facial disfigurement in cherubism can affect an individual's feelings of self-worth and be the source of bullying. However, one study reported that persons with cherubism were psychosocially well adapted and enjoyed a good quality of life [Prescott et al 2013].
Regression of the lesions occurs as they become filled with bone and remodel during the second and third decade of life. Although the facial disfigurement is expected to improve due to involution of the jaw lesions in early adulthood, this may not be the case for all individuals [Laroche et al 2022].
Dental abnormalities. In most affected persons, teeth are displaced, unerupted, hypoplastic, or absent, or they may appear to be floating in cyst-like spaces. Malocclusion, premature exfoliation of deciduous teeth, and root resorption have also been reported [Kozakiewicz et al 2001, Stoor et al 2017]. Orthodontic treatment is commonly required, as the jaw distortion leads to permanent dental abnormalities.
Respiratory manifestations can include obstructive sleep apnea and upper-airway obstruction caused by backward displacement of the tongue [Battaglia et al 2000, Ladhani et al 2003, Khirani et al 2013].
Orbital and ophthalmologic manifestations. Ophthalmic manifestations of cherubism vary greatly depending on the level of involvement of the maxilla [Mirmohammadsadeghi et al 2015, Yoo et al 2015]. In rare instances, enlargement of the maxilla and penetration of the stromal mass into the orbital floor can cause lower lid retraction, proptosis, strabismus, diplopia, globe displacement, and/or visual loss as a result of optic atrophy, retinal vein occlusion, and macular folds with scarring [Carroll & Sullivan 2001, Font et al 2003]. Prior reports of individuals with maxillary involvement leading to orbital mass effect have varied in their ophthalmic sequelae and age of occurrence, with occurrence ranging from age seven to 27 years [Colombo et al 2001, Ahmadi et al 2003].
Intellect and development are normal. Difficulty with pronunciation has not been reported as a significant problem [Prescott et al 2013].
Other
Pathophysiology. The cysts are filled with fibrous tissue that consists of stromal cells and osteoclast-like cells. The bone inflammatory findings are similar to other autoinflammatory syndromes with bone involvement, such as chronic recurrent multifocal osteomyelitis (CRMO) and deficiency of interleukin-1 receptor antagonist [Wipff et al 2011, Morbach et al 2013, Kadlub et al 2015, Bader-Meunier et al 2018]. One main difference in the pathology of cherubism when compared to CRMO is the degree of osteolysis, which is significantly more profound in cherubism [Wipff et al 2011]. NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1) immunohistochemistry on bone lesions may be helpful in defining a more aggressive form of the disease [Kadlub et al 2016].