Achondroplasia is caused by an altered fibroblast growth factor receptor 3 (FGFR3) gene. People develop this condition either through a new mutation of the FGFR3 gene or by inheriting the altered gene from a parent with achondroplasia. Of these two possible achondroplasia causes, the majority of cases (80 percent) are caused by a new gene mutation.
Achondroplasia Causes: An OverviewThere are two possible achondroplasia causes. One possible cause is a gene mutation of the fibroblast growth factor receptor 3 (FGFR3) gene located on chromosome 4. Achondroplasia can also be caused by inheriting the altered FGFR3 gene from a parent with the disorder.
Most people with achondroplasia have average-size parents, which means that the cause of achondroplasia in the majority of cases is a new mutation in the FGFR3 gene. Scientists do not know why this mutation occurs.
Achondroplasia can also be inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, one of the parents with achondroplasia passes the FGFR3 gene on to the child.
If one parent has achondroplasia, the children have a 50 percent chance of inheriting the altered FGFR3 gene. If both parents have achondroplasia, the children have a 1 in 4 chance of inheriting the gene from both parents. Newborns who inherit both genes are considered to have a severe form of achondroplasia where survival is usually less than 12 months after birth.
Although achondroplasia can be inherited, 80 percent of all achondroplasia cases are caused by a random gene mutation. In this case, the mutation involves the FGFR3 gene, situated on chromosome 4.
The protein made by the FGFR3 gene is a receptor that regulates bone growth by limiting the formation of bone from cartilage (a process called ossification), particularly in the long bones. Researchers believe that mutations in the FGFR3 gene cause the receptor to be overly active, which interferes with ossification and leads to the disturbances in bone growth seen with this disorder.
This theory is supported by the knock-out mouse model in which the receptor is absent, and so the negative regulation of bone formation is lost. The result is a mouse with excessively long bones and elongated vertebrae, resulting in a long tail. Achondroplastic mouse models are useful tools in developing potential treatments for achondroplasia in humans.
(Click Achondroplasia Genetics for more information about the link between achondroplasia and genetics.)