The discovery of a genetic mutation responsible for the childhood bone disorder cherubism was reported by researchers at the Harvard School of Dental Medicine and The Forsyth Institute in the June 1 issue of Nature Genetics.
In its mild forms, cherubism causes children to develop chubby cheeks and upward-looking eyes like those of cherubs in religious artwork. In its severe forms, cherubism can lead to excessive degradation of the jawbone. The bone tissue is replaced by soft-tissue masses, which can cause facial swelling that intrudes into the eye socket and forces the eyeballs to tilt upwards.
People who have cherubism also experience tooth malformations and loss, as well as chronic inflammation of lymph nodes. Many have difficulty chewing because of reduced jaw movement.
This genetic mutation primarily affects young children starting at about age three or four years, when the primary teeth normally begin to fall out. The disorder usually diminishes after puberty, and children who had a mild form generally do not exhibit external manifestations as adults.
Researchers discovered the mutation when they screened 25 genes located on chromosome 4p; the genes were obtained from the DNA of affected families in several countries. Researchers compared the genes from affected people with those of unaffected people.
Yasuyoshi Ueki, M.D., Ph.D., discovered a mutation in the SH3BP2 gene in affected people. The gene codes for a protein involved in the signaling mechanism of certain cells. Because cherubism involves both bone degradation and the growth of tumorlike cells, researchers hypothesized that the mutant protein functions differently in different kinds of cells.
For example, the mutant protein may activate osteoblasts that degrade the bone, while also activating osteoblasts or osteoblast precursors that normally build bone. These atypical osteoblasts proliferate, fill in cavities created by degraded bone and continue to grow as a fibrous tissue mass.
This discovery is "very exciting," because it could lead to potential therapies or prenatal diagnosis for the disorder, said researcher Bjorn Olsen, M.D., Ph.D.
