Causes of Multiple Epiphyseal Dysplasia
Mutations in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene can cause dominant multiple epiphyseal dysplasia. These genes provide instructions for making proteins that are found in the spaces between cartilage-forming cells (chondrocytes). These proteins interact with each other and play an important role in cartilage and bone formation. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.

The majority of individuals with dominant multiple epiphyseal dysplasia have mutations in the COMP gene. About 10 percent of affected individuals have mutations in the MATN3 gene. Mutations in the COMP or MATN3 gene prevent the release of the proteins produced from these genes into the spaces between the chondrocytes. The absence of these proteins leads to the formation of abnormal cartilage, which can cause the skeletal problems characteristic of dominant multiple epiphyseal dysplasia.

The COL9A1, COL9A2, and COL9A3 genes provide instructions for making a protein called type IX collagen. Collagens are a family of proteins that strengthen and support connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Mutations in the COL9A1, COL9A2, or COL9A3 gene are found in less than five percent of individuals with dominant multiple epiphyseal dysplasia. It is not known how mutations in these genes cause the signs and symptoms of this disorder. Research suggests that mutations in these genes may cause type IX collagen to accumulate inside the cell or interact abnormally with other cartilage components.

Some people with dominant multiple epiphyseal dysplasia do not have a mutation in the COMP, COL9A1, COL9A2, COL9A3, or MATN3 gene. In these cases, the cause of the condition is unknown.

Mutations in the SLC26A2 gene cause recessive multiple epiphyseal dysplasia. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of recessive multiple epiphyseal dysplasia.