Temporal lobe-predominant cortical dysplasia with mild cortical thickening in FOXG1 syndrome

Abstract

Background

Forkhead box G1 (FOXG1) gene syndrome is a neurodevelopmental disorder characterized by severe developmental delays, microcephaly, autistic features, epilepsy, and complex hyperkinetic-dyskinetic movement disorders. We present the case of a Japanese patient with microcephaly, cortical dysplasia with irregular gyri and mild cortical thickening in the temporal and frontal lobes, and a de novo heterozygous missense variant in FOXG1.

Case presentation

The patient was an 11-year-old Japanese boy who presented with microcephaly at 3 months of age. At 2 years and 10 months of age, he presented with frequent tonic seizures of unknown onset. Physical examination revealed microcephaly and dysmorphic features. He exhibited severe developmental delays and generalized hypotonia. Brain magnetic resonance imaging (MRI) revealed anterior hypogenesis of the corpus callosum, decreased cerebral volume, mildly delayed myelination, and cortical dysplasia with irregular gyri and mild cortical thickening, particularly in the temporal lobes. His seizures resolved after administering carbamazepine. Trio-based whole-exome sequencing analysis of the patient and his parents revealed a de novo heterozygous missense variant, NM_005249.5:c.688C>T p.(Arg230Cys), located in the forkhead DNA-binding domain of FOXG1, a recurrent variant that was finally diagnosed as FOXG1 syndrome.

Conclusions

Cortical malformation in FOXG1 syndrome is often observed in the frontal lobe. The cortical dysplasia and mild cortical thickening observed in our patient was predominantly in the temporal cortex, suggesting distinctive findings. These results provide new insights into brain malformations associated with FOXG1 syndrome.