Cherubism is a rare childhood fibro-osseous inherited condition, which affects the mandible and maxillary facial bones. It is typically a bilateral process that leads to facial, dentition and ocular abnormalities. The term Cherubism was invented in 1933 by Jones, who linked the full cheeks and the orbital displacement with the round faces and heavenly directed gaze of Renaissance cherubs. The disease has other synonyms that include: 1- familial multilocular cystic disease of the jaw; 2- familial fibrous dysplasia; 3- familial multiple giant cell lesions of the jaws.
Cherub (putto) is a baby angel with chubby cheeks and upward gaze.
The most common mode of inheritance for Cherubism is autosomal dominant with variable penetrance and expressivity. A few reports showed no apparent familial involvement. This disease is caused by mutations of the SH3 binding protein SH3BP2, found on chromosome 4p16.3. 
Orbital lesion specimens of lamellar and woven bone revealed osteoblast proliferation and scattered numerous multinucleated giant cells in a stroma that is mostly composed of spindle shaped fibroblasts. A few lesions have also shown reactive bone and small vascular channels.
The disease is characterized by symmetrical expansile, painless lesions affecting bilateral mandibles and sometimes bilateral maxillae. The submandibular and cervical lymph nodes are involved in the early stage. Occasionally the zygomatic arches can be involved. In early radiographic images, the angle of the mandible is the first to be affected with multilocular radiolucent changes that are asymptomatic, but can affect the development or eruption of permanent molars. The severity of the disease is highly variable, and may be mild with small mandibular lesions. The more progressive form comes with multiple mandibular lesions or mandibular and maxillary lesions that can cause extensive bone resorption and leave only a shell of cortical bone. As the disease progresses fibrous tissues can invade the floor of the orbits, which cause upward tilting and displacement of the eyes. Interestingly, after puberty most of the cases regress spontaneously. 
Cherubism affects mainly facial bones. Characteristic facial abnormalities usually include enlargement of mandibular bones, abnormal dentition and submandibular lymphadenopathy. Classically, it starts with the mandible angles then spreads to the whole mandible. Maxillary bones are involved in severe, late stages of the disease. Computed Tomography (CT) of the face may reveal fibrous bony dysplasia extending into the orbit, or bilateral symmetric extraconal lobulated bony masses that can displace the inferior and lateral recti muscles. Radiography reveals lucent expanded regions within mandible and maxilla with soap bubble appearance.
Representative radiology is available at https://radiopaedia.org/articles/cherubism
Ocular manifestations have a broad spectrum depending on the severity of maxillary involvement by the disease. The reported ocular manifestations of Cherubism may include:
Eyelid and Orbital
Posterior segment exam could reveal optic nerve impairment and atrophy, macular scarring, chorioretinal wrinkling, unusual high location of fovea, retinoschisis and subfoveal yellow vitelliform deposits.
Giant cell tumor of the jaw: Usually unilateral, and appears in patients between 20 to 40 years of age. Central giant cell granuloma of bone: Mainly affects the anterior mandible, and patients affected are usually between 10 to 30 years of age. Brown tumor of hyperparathyroidism: Histologically, giant cells are in zonal pattern, not scattered. Fibrous dysplasia: Histologically, C-shaped spicules on top of fibrous stroma is seen.
Generally, the disease is self-limiting and regresses with age. Thus, conservative treatment with a “wait and see approach” may be suitable until symptoms progress and surgical intervention becomes necessary. However, patients should be under the care of a multidisciplinary team, since they may need management of the facial lesions, cranio-facial surgeries, osseous recontouring and curettage, excision and debulking of maxillofacial masses, which will in turn improve the globe displacement, eyelid retraction, and strabismus. Patients can also develop airway obstruction, such as sleep apnea due to narrowing of the oral cavity, oropharynx, and nasopharynx caused by the facial bones overgrowth, that can be treated by tracheal tube insertion.
An Ophthalmologist familiar with this disease should be involved in the management of these patients. Eyeglasses or contact lenses can be prescribed for the large astigmatism. Lower eyelid retraction and proptosis requires control of corneal/conjunctival exposure. Severe orbital involvement calls for optic nerve monitoring, which may lead to earlier bony surgical intervention. Strabismus may improve after facial debulking surgeries or may necessitate strabismus surgery; however, this can be complicated given the typical bony regression as the patient ages. Therefore, routine ophthalmic screening is recommended in all Cherubism patients with maxillary involvement.
- Idemudia, A.B., Cherubism: Case report and review of literature. 2015. 17(1).
- Font, R.L., et al., Giant cell reparative granuloma of the orbit associated with cherubism. Ophthalmology, 2003. 110(9): p.1846-9.
- JONES, W.A., J. GERRIE, and J. PRITCHARD, Cherubism--familial fibrous dysplasia of the jaws. J Bone Joint Surg Br, 1950. 32-B(3): p. 334-47.
- Hawes, M.J., Cherubism and its orbital manifestations. Ophthal Plast Reconstr Surg, 1989. 5(2): p. 133-40.
- Kaugars, G.E., J. Niamtu, and J.A. Svirsky, Cherubism: diagnosis, treatment, and comparison with central giant cell granulomas and giant cell tumors. Oral Surg Oral Med Oral Pathol, 1992. 73(3): p. 369-74.
- Ueki, Y., et al., Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet, 2001. 28(2): p. 125-6.
- Kochar, I. and A. Ahmad, Early Presentation of Cherubism. Indian Pediatr, 2016. 53(8): p. 751.
- Ahmadi, A.J., G.E. Pirinjian, and B.S. Sires, Optic neuropathy and macular chorioretinal folds caused by orbital cherubism. Arch Ophthalmol, 2003. 121(4): p. 570-3.
- Carroll, A.L. and T.J. Sullivan, Orbital involvement in cherubism. Clin Exp Ophthalmol, 2001. 29(1): p. 38-40.
- Mirmohammadsadeghi, A., et al., Cherubism: report of three cases and literature review. Orbit, 2015. 34(1): p. 33-7.
- Colombo, F., et al., Orbital involvement in cherubism. Ophthalmology, 2001. 108(10): p. 1884-8.
- S. Irfan, A. Cassels-Brown, J. M. Hayward & A. M. Corrigan (1997) Orbital Cherubism, Orbit, 16:2, 109-112
- Kozakiewicz, M., W. Perczynska-Partyka, and J. Kobos, Cherubism--clinical picture and treatment. Oral Dis, 2001. 7(2): p. 123-30.
- Valiathan, A. and V.K. Prashanth, Cherubism: presentation of a case. Angle Orthod, 1997. 67(3): p. 237-8.
- Robbins, S. and I. Kozak, New retinal findings in cherubism. Retin Cases Brief Rep, 2010. 4(2): p. 146-9.
- Yoo, S.H., et al., Ophthalmic manifestations of cherubism. J AAPOS, 2015. 19(1): p. 70-2.
- Nicholas Zachariades 1, S.P., Assimina Xypolyta, Ioannis Constantinidis, Cherubism. 1985. 14(2).
- Southgate, J., et al., Study of the cell biology and biochemistry of cherubism. J Clin Pathol, 1998. 51(11): p. 831-7.
- Jakobiec FA, Bilyk JR, Font RL. Orbit. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook, 4th Ed. Philadelphia: Saunders, 1996, vol 2459-860.
- Divya Mehrotra, A.K., Cherubism: Case Report with Review of Literature. Journal of Maxillofacial and Oral Surgery, 2011.