Natural history of epilepsy in FOXG1 Syndrome

Abstract

Background: FOXG1 syndrome is rare neurodevelopmental disorder with microcephaly, brain malformations, epilepsy, and cognitive and motor disabilities as major features. Knowledge of the clinical features is primarily from case series and a foundation sponsored registry. We expand insight into epilepsy in FOXG1 syndrome by examining longitudinal data from 94 individuals from a multi-site natural history study and local cohorts.

Methods: Clinical information on severity, seizure type, and seizure features was collected from 68 individuals enrolled in the Rett Syndrome and Related Disorders Natural History Study and extracted via retrospective chart review from 15 individuals seen at the Children's Hospital of Philadelphia Rett Syndrome Center of Excellence and 11 individuals from Children's Hospital of Colorado. Genotype-phenotype and other correlations were assessed using non- and semi-parametric analyses.

Results: 78.7 % of participants had seizures, beginning at a median age of 1.0 years. Individuals were followed for a median of 4.9 years after first seizure onset. Taken independently, over 70 % of seizures were partial or tonic-clonic, occurred less than weekly, and lasted less than 5 min. 1/3 of seizures resolved in a median time and age of 1.1 and 3.3 years. Age had a weak non-linear association with average seizure frequency, and, for those with seizures, smaller head circumference correlated with increased disease severity.

Conclusions: We further characterize disease severity and epilepsy in FOXG1 syndrome and demonstrate that smaller head circumferences are associated with more severe disease and age is weakly non-linearly correlated with average seizure frequency. This information will improve clinical care and aid therapeutic development.

Keywords: Developmental Encephalopathy; Epilepsy; FOXG1; FOXG1 Syndrome; Seizure.