Craniometaphyseal dysplasia, autosomal dominant

Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the ANKH gene. The ANKH gene provides instructions for making a protein that is present in bone and transports a molecule called pyrophosphate out of cells. Pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in developing bones. The ANKH protein may have other, unknown functions.

Mutations in the ANKH gene that cause autosomal dominant craniometaphyseal dysplasia may decrease the ANKH protein's ability to transport pyrophosphate out of cells. Reduced levels of pyrophosphate can increase bone mineralization, contributing to the bone overgrowth seen in craniometaphyseal dysplasia. Why long bones are shaped differently and only the skull bones become thicker in people with this condition remains unclear.

Autosomal dominant craniometaphyseal dysplasia is inherited in an autosomal dominant pattern, which means one altered copy of the ANKH gene in each cell is sufficient to cause the disorder. Individuals with autosomal dominant craniometaphyseal dysplasia typically have one parent who also has the condition. Less often, cases result from new mutations in the gene and occur in people with no history of the disorder in their family.