FOXG1

FOXG1 (forkhead box G1) is a transcription factor belonging to the forkhead box family. It plays a critical role in early brain development, especially in the forebrain and the development of the cerebral cortex. The encoded protein binds DNA and regulates the expression of genes involved in neurodevelopment.

Expression of FOXG1 is highest in the developing telencephalon. It is involved in maintaining neural progenitor populations, guiding the timing of neurogenesis, and contributing to regional specification within the forebrain. Through these activities, FOXG1 helps shape neural circuits that underpin cognition and behavior.

Clinical significance: Pathogenic variants in FOXG1, including loss-of-function mutations and deletions, cause FOXG1 syndrome. This neurodevelopmental disorder is characterized by congenital microcephaly, severe global developmental delay, impaired or absent speech, seizures, hypotonia, and distinctive facial features. Behavioral features may include autistic-like traits in some individuals.

Genetics and variants: FOXG1-related conditions are rare. Haploinsufficiency is a common mechanism. In addition to deletions and point mutations, duplications or altered regulation of FOXG1 have been reported in related neurodevelopmental phenotypes, illustrating the gene's dosage sensitivity.

Research and model systems: The mouse homolog Foxg1 is essential for forebrain development; knockout studies show severe telencephalic defects and early lethality, highlighting the gene’s fundamental role. Human cellular models and patient-derived cells are used to study FOXG1 function and test potential therapies.

Diagnosis and management: Diagnosis relies on genetic testing in individuals with compatible neurodevelopmental features. There is currently no cure; management is supportive and multidisciplinary, including developmental therapies, seizure control, and careful monitoring of growth and health. Genetic counseling is advised for families.