Which are the causes of Cherubism?

Cherubism is a rare genetic disorder that primarily affects the bones of the face and jaw. It is characterized by abnormal growth and development of these facial bones, resulting in a distinctive appearance. While the exact cause of Cherubism is not fully understood, it is believed to be primarily caused by genetic mutations.

Genetic Mutations: Cherubism is typically caused by mutations in the SH3BP2 gene, which provides instructions for producing a protein involved in cell signaling and bone development. These mutations are usually spontaneous, meaning they occur randomly during the formation of reproductive cells or early embryonic development. In some cases, Cherubism can be inherited from a parent who carries the mutated gene.

Autosomal Dominant Inheritance: Cherubism follows an autosomal dominant pattern of inheritance, which means that a child has a 50% chance of inheriting the disorder if one parent carries the mutated gene. However, not all individuals with the mutated gene will develop Cherubism, and the severity of the condition can vary even among affected family members.

Cell Signaling Disruption: The SH3BP2 gene mutation disrupts normal cell signaling processes, leading to abnormal bone remodeling and excessive bone resorption. This results in the characteristic overgrowth of fibrous tissues in the facial bones, particularly the lower jaw and cheeks.

Impact on Osteoclasts: Osteoclasts are specialized cells responsible for breaking down and remodeling bone tissue. In Cherubism, the mutated SH3BP2 protein affects the function of osteoclasts, causing them to become overactive and leading to excessive bone resorption. This imbalance between bone resorption and formation contributes to the abnormal bone growth seen in Cherubism.

Variable Expressivity: Cherubism can vary in its severity and presentation, even among individuals with the same genetic mutation. Factors such as age, hormonal influences, and other genetic or environmental factors may influence the extent of facial bone involvement and the overall appearance of the condition.

Non-hereditary Cases: In rare cases, Cherubism can occur without a family history of the disorder. These cases are thought to result from spontaneous mutations in the SH3BP2 gene during early development or from other genetic or environmental factors that have not yet been fully identified.

While the causes of Cherubism are primarily genetic, the exact mechanisms by which the SH3BP2 gene mutation leads to the characteristic facial bone abnormalities are still being studied. Ongoing research aims to further understand the underlying processes involved in Cherubism, which may eventually lead to improved diagnostic methods and potential treatments for this rare disorder.