Cherubism

Cherubism is a rare inherited fibro osseous disorder of the jaws, with bilateral, painless, symmetrical swelling of the mandible, and sometimes the maxilla, that begins in early childhood. It improves after puberty in most.

It is usually autosomal dominant, with variable expression, and almost complete penetrance in males and about 50 to 70% in females. Onset is between 2 and 5 years of age.

Pathophysiology. Gain-of-function mutations in the SH3BP2 gene (about 80% of cases) increase signalling in osteoclasts and macrophages, with raised TNF-alpha, so that giant cells accumulate and bone is resorbed and replaced by vascular fibrous tissue.

Lesions slow down at puberty and the fibrous tissue is replaced by bone over years. Cases with no SH3BP2 mutation exist.

Painless, firm, bilateral swelling of the angle and ramus of the mandible, giving a full cheeked, cherubic look, with submandibular lymph node enlargement. Maxillary involvement can push the orbital floor upward and expose a rim of sclera under the iris (upward gaze).

Teeth are displaced, absent, unerupted or exfoliated early. Severe disease causes tongue displacement, airway narrowing, speech and swallowing problems, and orbital compression with visual loss.

Grades by extent range from mandibular only to the whole jaws and orbits. Proptosis, visual change or breathing difficulty need urgent assessment.

• Clinical diagnosis from the age, symmetrical swelling and family history.
• Panoramic radiograph and CT: bilateral multilocular, expansile, well defined radiolucencies in the posterior mandible, with thinned cortices and displaced tooth germs, and possible involvement of the maxillary tuberosity and orbital floor.
• Biopsy when the diagnosis is unclear: multinucleated giant cells in a vascular fibrous stroma, with eosinophilic perivascular cuffing.
• SH3BP2 gene testing for confirmation and family counselling.
• Serum calcium, phosphate, alkaline phosphatase and parathyroid hormone to exclude hyperparathyroidism.
• Ophthalmic assessment including visual acuity and fields when the maxilla or orbit is involved.

Differential diagnosis.

• Fibrous dysplasia
• Central giant cell granuloma (usually unilateral)
• Brown tumour of hyperparathyroidism
• Noonan syndrome and neurofibromatosis type 1 with giant cell lesions
• Jaffe-Campanacci and other multifocal fibro osseous syndromes
• Ameloblastoma and odontogenic myxoma
• Langerhans cell histiocytosis and lymphoma

• Most children need observation only, with clinical and radiographic review, because lesions regress after puberty.
• Surgery (curettage, contouring) is reserved for severe deformity, functional problems, visual or airway risk, preferably after growth is complete, since lesions can regrow if surgery is done in childhood.
• Orbital compression or airway compromise needs urgent surgery or drug therapy.
• Medical therapy in rapidly progressive, severe disease, by specialist teams only, from case reports and small series: calcitonin, denosumab, imatinib or tacrolimus. Evidence is limited and there is no established dose. Denosumab is used with caution in children because of rebound hypercalcaemia after stopping.
• Orthodontic and prosthetic care for missing teeth, and speech and swallowing therapy when needed.
• Genetic counselling for the family, with a 50% risk of passing on the variant.

Monitoring. Clinical and radiographic review every 6 to 12 months during growth. Visual assessment at least annually in orbital disease.

Referral and escalation. Refer to oral and maxillofacial surgery, clinical genetics and paediatrics. Refer to ophthalmology for any orbital signs and to ENT or anaesthesia for airway concern.