FOXG1

The FOXG1 gene provides instructions for making a protein known as forkhead box G1. This protein is a transcription factor, which means it helps regulate the activity of other genes. Specifically, the forkhead box G1 protein acts as a transcriptional repressor, turning off (repressing) the activity of certain genes when they are not needed. Researchers believe that this protein plays an important role in brain development, particularly in a region of the embryonic brain known as the telencephalon. The telencephalon ultimately develops into several critical structures, including the two cerebral hemispheres (which control most voluntary activity, language, sensory perception, learning, and memory).

Rett syndrome - caused by mutations in the FOXG1 gene

At least 18 mutations in the FOXG1 gene have been found to cause the congenital variant of Rett syndrome. This rare condition is characterized by severe intellectual disability, abnormally small head size (microcephaly), jerky limb movements, seizures, and absent language. The signs and symptoms of the congenital variant become apparent in early infancy; unlike the classic form of Rett syndrome, there is no early period of apparently normal development.

Most of the identified FOXG1 gene mutations prevent the production of any functional forkhead box G1 protein. A few other mutations change single protein building blocks (amino acids) in a critical region of the protein. Studies suggest that a loss of forkhead box G1 function disrupts normal brain development, leading to intellectual disability and the other features of the congenital variant of Rett syndrome.

other disorders - caused by mutations in the FOXG1 gene

A few people have been found to have an extra copy (duplication) of the part of chromosome 14 that contains the FOXG1 gene. People with these duplications have had recurrent seizures or spasms starting in infancy, intellectual disability, and severe speech impairment. Duplications of the FOXG1 gene have also been identified in several infants diagnosed with West syndrome, a condition characterized by recurrent seizures that begin in infancy, severe to profound intellectual disability, and related brain abnormalities.