FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants

First Author: Diana Mitter (More authors)
Journal: Genetics in Medicine
Year: 2016

The authors compared the clinical features of 83 individuals to determine whether any patterns could be identified based on the types of observed pathogenic variants (frameshift, missense, nonsense).

In general, those individuals with truncating variants in the N-terminal (beginning) domain of FOXG1 had a more severe presentation. Individuals with pathogenic missense variants in an evolutionarily conserved region of the forkhead
DNA-binding domain had milder presentations. This article also reports if and when individuals achieved developmental milestones: 45% were able to sit unassisted at a mean age of 28 months; 15% were able to walk unsupported at a mean age
of 53 months; functional hand use observed in 40%; 21% had some verbal expression (note that age at last follow-up was not consistent, and different for each individual).

A range of epilepsy diagnoses were reported, with a wide range in the age of onset (3 to 168 months). There does not seem to be a characteristic seizure type.

Importantly, 5 families have now been documented with presumed parental mosaicism; the authors recommend that prenatal genetic diagnosis be offered to families with a child who has FOXG1 syndrome.

Significance
First publication demonstrating genotype-phenotype correlations (i.e. the type of FOXG1 mutation impacts clinical severity), and uses a new standardized assessment of clinical severity in the largest published population of individuals with FOXG1 syndrome.