Cherubism

Cherubism is a rare genetic disorder primarily affecting the bones of the jaw and face, typically manifesting in early childhood. The name derives from the condition’s characteristic appearance—full, rounded cheeks and an upward gaze reminiscent of cherubic figures in Renaissance art (1). While it is classified as a bone disorder, cherubism is technically a fibro-osseous condition involving the abnormal development and remodeling of bone and fibrous tissue in the mandible (lower jaw) and maxilla (upper jaw). Though often benign and self-limiting, cherubism can significantly impact facial appearance, dental development, and, in severe cases, respiratory or vision-related functions (1).

Symptoms

The symptoms of cherubism usually become noticeable between the ages of 2 and 7, and they can range from mild to severe. Common signs include (1):

• Facial swelling: Symmetrical, painless enlargement of the jawbones, giving the child a full-faced appearance.
• Dental abnormalities: Delayed eruption of teeth, missing or displaced teeth, and misalignment of the jaw.
• Cheek fullness and upward eye gaze: As lesions enlarge, they push the eyes upward and outward, resulting in a “heavenward gaze.”
• Bone lesions: Cyst-like growths filled with fibrous tissue develop in the jawbones.
• Speech and chewing difficulties: In more advanced cases, the jaw abnormalities can interfere with normal oral function.
• Eye or nasal obstruction: In severe forms, the lesions may extend into the orbital or nasal cavities, leading to vision or breathing problems.

Symptoms often stabilize or regress after puberty, and some individuals may see significant improvement in facial appearance by adulthood (2).

Causes

Cherubism is primarily caused by mutations in the SH3BP2 gene, located on chromosome 4. This gene plays a role in regulating the activity of certain cells involved in bone remodeling, particularly osteoclasts (cells that break down bone tissue). The mutation leads to increased osteoclast activity and an overproduction of fibrous tissue in the jawbones, resulting in the replacement of normal bone with lesions (2).

Cherubism follows an autosomal dominant inheritance pattern, meaning only one copy of the altered gene from an affected parent can cause the condition. However, spontaneous mutations can also occur in individuals with no family history of the disorder (1).

Risk Factors

The main risk factor for cherubism is genetic inheritance. A child has a 50% chance of developing the condition if one parent carries the mutated gene. Beyond this genetic link, there are no known environmental or lifestyle factors that contribute to the development of cherubism (3).

In families with a history of cherubism, genetic counseling may be recommended for prospective parents (3).

Diagnosis

Diagnosis of cherubism is usually made based on (1):

• Clinical Examination: Doctors may observe characteristic facial swelling and dental issues in young children.
• Radiological Imaging: X-rays, CT scans, or MRIs reveal cystic lesions and abnormal bone growth in the mandible and maxilla. A classic finding is bilateral, multilocular radiolucencies (areas that appear dark on imaging due to less bone density).
• Histopathology: A biopsy of the affected bone shows fibrous tissue with multinucleated giant cells, confirming the diagnosis.
• Genetic Testing: DNA testing can identify mutations in the SH3BP2 gene to confirm hereditary cherubism.

Cherubism must be differentiated from other fibro-osseous lesions, such as fibrous dysplasia or giant cell granulomas, which may present similarly (3).

Treatment Options

Treatment for cherubism depends on the severity of symptoms (3):

1. Observation: Many mild to moderate cases do not require treatment, especially if the condition shows signs of self-resolution after puberty. Regular monitoring by an orthodontist or oral surgeon is typically recommended.
2. Orthodontic Treatment: Corrective braces or aligners can help manage dental misalignment. Delayed tooth eruption may require intervention to assist normal dental development.
3. Surgical Intervention:
   • Curettage or recontouring: In cases of significant jaw deformity or functional impairment, surgical reshaping of the jawbones may be needed.
   • Bone grafting: Sometimes used to reconstruct facial structure if lesions have caused major bone loss.
   • Orbital decompression: In rare cases, if lesions press against the eyes or airways, surgery may be required to relieve the pressure.
4. Pharmacological Therapy: Though still under investigation, some drugs such as calcitonin and interferon-alpha have been trialed with limited success in reducing lesion size or osteoclastic activity (3).
5. Speech Therapy: If jaw deformities affect speech, therapy can help improve articulation and communication skills.

Living With or Prevention

Living with cherubism involves regular follow-ups with a multidisciplinary medical team, including pediatricians, oral surgeons, orthodontists, and genetic counselors. While the condition can cause psychosocial challenges due to facial appearance, many individuals lead normal, healthy lives, especially as symptoms often improve in adulthood (2).

Support from mental health professionals, school counselors, and peer support groups can help children and adolescents cope with social anxiety or self-esteem issues.

Prevention is not currently possible due to the genetic nature of the condition. However, prenatal genetic testing and early diagnosis in families with a known history can help prepare parents and initiate early monitoring or interventions (1).

References

1. Mehrotra D, Kesarwani A, Nandlal. Cherubism: case report with review of literature. J Maxillofac Oral Surg. 2011 Mar;10(1):64-70. doi: 10.1007/s12663-010-0164-y. Epub 2011 Mar 22. PMID: 22379324; PMCID: PMC3177504.
2. Kaur M, Shah S, Babaji P, Singh J, Nair D, Kamble SS. Cherubism: A rare case report. J Nat Sci Biol Med. 2014 Jul;5(2):488-91. doi: 10.4103/0976-9668.136283. PMID: 25097445; PMCID: PMC4121945.
3. Papadaki ME, Lietman SA, Levine MA, Olsen BR, Kaban LB, Reichenberger EJ. Cherubism: best clinical practice. Orphanet J Rare Dis. 2012 May 24;7 Suppl 1(Suppl 1):S6. doi: 10.1186/1750-1172-7-S1-S6. Epub 2012 May 24. PMID: 22640403; PMCID: PMC3359956.