Epilepsy phenotypes associated with MAP1B-related brain malformations

Recently, studies on whole-exome sequencing (WES) of large cohorts of people with periventricular heterotopia (PVH) have reported an association with loss-of-function variants in the MAP1B gene. However, neurological phenotypes of these patients remain poorly characterized. Four family members with seizures beginning in early childhood were evaluated. Integrated genomic analysis with WES and microarray was performed. Affected family members had various combinations of: febrile, fever-triggered and afebrile seizures; photo-sensitivity; comorbid mild developmental delays; obsessive-compulsive behaviors; and poor attention span. Neuroimaging showed PVH, corpus callosum abnormalities, and perisylvian polymicrogyria. A novel heterozygous frameshift variant in MAP1B was found in all affected family members. This report extends the clinical and neuroimaging phenotypes associated with MAP1B pathogenic variants. MAP1B variants may be considered in patients with febrile and afebrile seizures if characteristic neuroimaging, particularly PVH, is observed.