Cherubism

Cherubism is caused by changes (mutations) in the SH3-domain binding protein 2 ( SH3BP2) gene on chromosome 4. The protein encoded by SH3BP2 is important for bone metabolism and remodeling. Researchers believe that SH3BP2 mutations lead to an overly active version of the protein that alters critical signaling pathways in cells associated with the maintenance of bone tissue and in certain immune system cells. The overactive protein may cause inflammation in the bones of the jaw, triggering the production of too many osteoclasts (the cells that repair bone). Too many of these cells contribute to the abnormal breakdown of bone tissue in the upper and lower jaw. A combination of bone loss and inflammation likely leads to the cyst-like growths seen in cherubism.

About 80% of people with cherubism have a mutation in the SH3BP2 gene. The cause of the condition in the remaining 20% of cases remains unknown.

Cherubism is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. The proportion of cases of cherubism caused by de novo mutation is unknown since variable expressivity and reduced penetrance are observed in this condition.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Cherubism is a rare disorder characterized by progressive, painless, bilateral swelling of the jaw during childhood. This fibro-osseous (bone structure) condition is self-limiting, with symptoms typically resolving in adulthood. Diagnosis is based on a combination of clinical signs, family history, radiographic findings (panoramic x-rays, CT scan), biopsy, and genetic testing. Cherubism is inherited in an autosomal dominant fashion and is caused by mutations in the SH3BP2 gene. Treatment tends to be conservative (wait-and-see), with surgery reserved for the most severe cases.

Yes. Again, only 80 percent of people with cherubism have an identifiable mutation in the SH3BP2 gene. In the remaining cases, the cause is likely genetic, but unknown. Individuals who do not have an identifiable genetic cause can still have children with cherubism.

There may be a number of reasons that might explain your family history. One possible explanation is that there are members in your family who have cherubism, but who were never diagnosed because their signs and symptoms were very mild. Alternatively, you could be the first member in your family with cherubism because a mutation occurred in your mother's egg or your father's sperm or in the fertilized egg; this phenomenon is called a de novo mutation.

Testing is available for SH3BP2, the gene that has been identified in about 80 percent of people with cherubism. Even if a person tests negative for disease-causing mutations in the SH3BP2 gene, a genetic cause is still likely. At this time, the other gene(s) that may be associated with cherubism have not been identified; therefore, genetic testing is unavailable.

To find out your specific chances of having a child with cherubism, we recommend speaking with a genetics professional. Such a professional can review your medical and family history to determine your specific chances. Below we provide a list of online resources that can assist you in locating a genetics professional. Although we cannot provide specific risks, we can say that, in general, cherubism is inherited in an autosomal dominant fashion, which means that having a change (mutation) in only one coy of the responsible gene is each cell is enough the cause features of the condition.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can learn more about genetic consultations from Genetics Home Reference.