MCDS is caused by an error in the body’s genetic code. The error is located on the COL10A1 gene which creates a protein known as collagen X – or collagen 10. This mutation is a dominant trait, meaning that only one of the two copies of an individual’s COL10A1 needs to be a mutant in order for them to develop MCDS. Consequently, if you have MCDS there is a 50% chance of passing it on to your child.
Collagen is a protein that is used to form the hard structure of bone. This means that to function, it needs to be moved outside of the cells and into the surrounding bony matrix. In MCDS, errors in the gene for collagen X mean that cells build the protein incorrectly. This causes the protein to get trapped inside the cell. Specifically, the protein gets trapped within a part of the cell known as the endoplasmic reticulum (or ER), which become stressed (ER stress). Over time this is very bad for the health of cells that produce a lot of collagen X. It stops the cells functioning in a normal way, and ultimately leads to cell death.
Collagen X is only produced at the ends of bones in the cartilage growth plate. This is where cartilage is turned into bone when bones are growing. The end portions of long bones are known as metaphyses, and are responsible for the first part of the name of metaphyseal chondrodysplasia. In MCDS patients, ER stress hampers the growth of the bones as the cells in the growth plate stop changing – also known as differentiating – from cartilage to bone. This causes the characteristics of the condition: shortened limbs, bowed long bones, and flaring of the metaphyses.