ARX

The ARX gene provides instructions for producing a protein that regulates the activity of other genes. On the basis of this action, the ARX protein is called a transcription factor. The ARX gene is part of a larger family of homeobox genes, which act during early embryonic development to control the formation of many body structures. Specifically, the ARX protein is believed to be involved in the development of the pancreas, gastrointestinal tract, testes, and brain.

X-linked lissencephaly - caused by mutations in the ARX gene

There are more than 20 mutations in the ARX gene that cause X-linked lissencephaly with abnormal (ambiguous) genitalia. These mutations usually result in a nonfunctional ARX protein. As a result, the ARX protein cannot perform its role in regulating the activity of certain genes. In addition to impairing normal brain development, a shortage of functional ARX protein can also disrupt normal function in the pancreas and the testes, leading to the signs and symptoms of X-linked lissencephaly with ambiguous genitalia.

other disorders - caused by mutations in the ARX gene

Different mutations in the ARX gene can cause a variety of conditions that all impair brain function. People who have a condition caused by a mutation in the ARX gene usually have intellectual disability. Most of these conditions also involve seizures and abnormal muscle movements, such as stiffness or spasms. Unlike X-linked lissencephaly, none of these ARX-related conditions have associated structural brain abnormalities.

Some ARX mutations result in intellectual disability with other neurological problems. Because the ARX gene is on the X chromosome, this condition is known as X-linked mental retardation (XLMR). Other mutations result in conditions with symptoms that vary in severity. X-linked infantile spasm syndrome (a form of epilepsy sometimes called West syndrome) and X-linked myoclonic epilepsy with mental retardation and spasticity both involve intellectual disability and epilepsy. Partington syndrome involves mild to moderate intellectual disability and abnormal muscle stiffness (spasticity) with involuntary tensing of the muscles (dystonia). It is not clear why different mutations in the ARX gene cause this array of conditions.