MSX1

The MSX1 gene is often deleted in people with Wolf-Hirschhorn syndrome. The features of this condition include a characteristic facial appearance, delayed growth and development, intellectual disability, and seizures. 

A loss of the MSX1 gene probably disrupts the regulation of several other genes, particularly genes involved in the development of the mouth and teeth. Researchers believe that a deletion of the MSX1 gene disrupts the formation of oral structures in early development, leading to missing teeth and other dental abnormalities. A loss of the MSX1 gene probably also causes an opening in the roof of the mouth (cleft palate) and/or a split in the upper lip (cleft lip) seen in some people with Wolf-Hirschhorn syndrome.

MSX1 gene variants (also called mutations) are associated with abnormalities of mouth and tooth development. For example, changes in this gene contribute to some cases of cleft lip and/or cleft palate in people who do not have Wolf-Hirschhorn syndrome. These genetic variations have been associated with isolated cleft lip and cleft palate in several different populations worldwide. MSX1 gene variants appear to be one of many genetic and environmental factors that play a role in oral clefting.

At least six MSX1 gene variants are responsible for oligodontia, a condition in which multiple teeth fail to develop. Some individuals with MSX1 gene variants have a combination of oligodontia and cleft lip and/or cleft palate. Variants in the MSX1 gene likely reduce the amount of functional MSX1 protein within cells, which disrupts the early development of structures in the mouth.

Another variant in the MSX1 gene has been found to cause Witkop syndrome (also known as tooth-and-nail syndrome). This rare condition is characterized by missing teeth and abnormalities of the fingernails and toenails. The MSX1 gene variant mutation responsible for Witkop syndrome leads to the production of an abnormally short, nonfunctional version of the MSX1 protein.  A loss of this protein disrupts the formation of the teeth and nails during early development.