FOXG1 Syndrome is a rare neuro-developmental condition associated with mutations in the forkhead box G1 (FOXG1) gene. A de novo pathogenic variant in FOXG1 was first discovered via fluorescence in situ hybridization and southern blot hybridization in a girl with severe cognitive disability associated with complete agenesis of the corpus callosum and microcephaly in 2005. 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. 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 the largest part of the brain (the cerebrum), which controls most voluntary activity, language, sensory perception, learning, and memory.
There is a wide variation in both the symptoms and severity experience by patients with FOXG1 Syndrome.
- Symptoms present from birth
- Affects both male and female
- Agenesis of the corpus callosum
- Feeding Difficulties
- Sleep difficulties
- Learning Disability
- Dismorphic Features
- Cortical Visual Impairment
- Inability to control body movements
- Unable to walk or talk (though some do walk and are able to communicate with speech)
FOXG1 is diagnosed through genetic testing in individuals suspected of having the syndrome. A medical genetic test is most often carried out by taking a blood sample from the patient’s arm. The genetic material is extracted from blood cells in the laboratory and used in the testing process.
Parents will often undergo a Carrier Test to see if they have passed the syndrome on to the child. In the majority of cases of FOXG1 Syndrome the genetic mutation was de novo which means the parents did not carry the mutation.Geneticists will meet with families to discuss the diagnosis and explain exactly what type of mutation the patient has.
Types of Genetic Mutation
- Missense – This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
- Nonsense mutation – A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
- Insertion – An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.
- Deletion – A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).
- Duplication – A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.
- Frameshift mutation – This type of mutation occurs when the addition or loss of DNA bases changes a gene's reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.