SickKids

Paediatric Laboratory Medicine
Paediatric Laboratory Medicine
print        

Cherubism Molecular Analysis

Background
Who should be tested
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
For More Information

Background

Cherubism is a rare autosomal dominant condition of the mandible and maxilla. It causes round cheeks and jaws with slight upward turning of the eyes giving a facial appearance reminiscent of the angelic cherubs. The basis for the fullness of cheeks and jaws is a non-neoplastic fibrous dysplasia within the maxilla and mandible. Both ends of the spectrum, mild clinically unrecognized cases, and severe cases with extensive bone loss are seen. In some severe cases, the marked deformation results in chewing, speech, and swallowing difficulties and in rare cases, severe orbital involvement leading to diplopia may occur. Patients with Cherubism may show variability in clinical features due to incomplete penetrance and variable expressivity. In males the penetrance is close to 100% but in females only 50-75%.

The gene for Cherubism is SH3BP2, which has been localized to chromosome 4p16.3. Eleven different missense mutations for Cherubism have been described so far, all of them have been found in exon 9 of the SH3BP2 gene.

Cherubism is present when an individual has one copy of the defective gene. Affected individuals have a 50% chance of transmitting the disorder to each child. There is a 50% chance that the affected individual’s offspring will not be affected with Cherubism.

Who should be tested?

  • individuals clinically suspected of being affected with Cherubism
  • relatives of probands with identified SH3BP2 mutations
  • pregnancies at risk due to family history of Cherubism

Testing Methodology

Direct Mutation Analysis: All samples are analyzed by direct sequence analysis of the exons and intron/exon boundaries of the SH3BP2 gene.

Potential Outcomes & Interpretation of Test Results

SH3BP2 Gene MutationS
allele 1/ allele 2

Explanation

none detected / none detected

This result is unable to confirm a diagnosis of Cherubism.

mutation detected
/ none detected

This result confirms a diagnosis of Cherubism.

Cautions

  • Current molecular testing will not detect all possible mutations in this gene. A negative result does not rule out the possibility that the individual carries a rare SH3BP2 mutation not detected by the assay.
  • Test results should be interpreted in the context of clinical findings, family history, ethnic background and other laboratory data.
  • This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical purposes.

For More Information