FOXG1 syndrome is a rare, severe autosomal dominant neurodevelopmental disorder caused by heterozygous mutations in the FOXG1 gene, which is a transcription factor important for brain development. FOXG1 is involved in neuronal proliferation, migration and organization within the cortex as well as the corpus callosum and hippocampus. In addition, it regulates GABA signalling.
The syndrome is caused by de novo variants including frameshift, nonsense, and missense variants, as well as whole-gene deletions or duplications. On rare occasions, the mutation may be inherited from unaffected parents due to somatic mosaicism.
The estimated prevalence is approximately 1 in 30,000, affecting both males and females equally. Clinically, the disorder presents within the first year of life and is characterized by severe global developmental delay and intellectual disability, postnatal microcephaly, epilepsy (infantile spasms, focal, generalized tonic, myoclonic and Lennox-Gastaut syndrome), hyperkinetic movement disorders (chorea, dystonia, athetosis, hand stereotypies), feeding difficulties, cortical visual impairment, and autism-related features such as poor eye contact and social interactions. Neuroimaging reveals structural brain abnormalities, such as agenesis or hypogenesis of the corpus callosum.
While there is no cure at this time, there is much ongoing research into gene therapy, genome editing, and antisense oligonucleotide strategies in addition to current symptoms management strategies.
FOXG1