Focal Cortical Dysplasia in a Family with KCNQ3 Mutation

Case Study: This study presents cases of patients suffering from focal cortical dysplasia (FCD) in a family with KCNQ3 mutation.

Background: Mutations in the KCNQ3 gene have been described to cause benign focal epilepsies of childhood and, casuistically, also autism-spectrum disorder with and without epilepsies. Here, we report two siblings with heterozygous KCNQ3 mutations, who suffered from epilepsy; MRI of the boy also visualized a frontal FCD.

Case Reports: The girl showed benign epilepsy typical potentials of childhood, the occipital regions during a sleep EEG at the age of 4 years. At the age of 6 years, she developed typical Rolandic epilepsy with seizures and centrotemporal spikes.

Her younger brother developed first seizures at the age of 2 years, which initially did not respond to antiepileptic medication. MRI visualized a right frontal FCD, the EEG showed a bifrontal and bi-occipitotemporal bioelectrical status epilepticus. Also, because of the rapid cognitive decline and increasing autistic features, epilepsy surgery was considered. With a combination of sulthiame, valproate, and rufinamide, however, the boy became seizure-free; the autistic symptoms disappeared, and cognitive development started to normalize.

Genetic studies revealed heterozygous KCNQ3 mutations in both the siblings, and also heterozygous SCN8A mutations of unclear significance in both.

Discussion: In the girl, the typical rolandic epilepsy is well compatible with the KCNQ34 mutation. The more severe course with initially pharmacorefractory epilepsy with severe autistic features in her brother might be explained by the (additional) FCD. Genetic factors can influence the course of the epilepsy in patients with FCDs and can be important for the therapeutic concept.