Abstract:

Objective To investigate the clinical phenotypic and genotypic features of FOXG1-related syndrome. Methods The clinical data and genetic test results of 3 children with FOXG1-related syndrome treated in our hospital from January 2018 to January 2022 were analyzed retrospectively. Results Three children with FOXG1-related syndrome were included, all male, with postnatal onset. All the patients had early-onset dyskinesia, global developmental delay and microcephaly. Whole exome sequencing showed that all 3 patients had the pathogenic variation of FOXG1 gene. Brain magnetic resonance imaging (MRI) was characterized by hypoplasia of the frontal cortex and/or corpus callosum or delayed myelination. Case 1 had a frameshift mutation of c.256dupC (p.Gln86Profs*35) at the N-terminal domain site in the FOXG1 gene, and case 2 had a nonsense mutation of c.595G>T (p.Glu199*) in the fork-head binding domain of FOXG1 gene. A nonsense of c.1178C>A (p.S393*) was found in the JARID1B binding domain of FOXG1 gene in case 3. Case 3 had a milder clinical phenotype and brain abnormalities than the other 2 patients. The variations of cases 2 and 3 had not been previously reported in the literature, which expanded the gene spectrum of the disease. Conclusions FOXG1 variation should be considered for individuals with early-onset dyskinesia, developmental delay, microcephaly and characteristic brain imaging lesions.

Key words: FOXG1gene, movement disorder, developmental delay, microcephaly