Treatment of KCNQ2 Related Epilepsy

Background: Epilepsy disorders due to a mutation in the KCNQ2 gene comprise both early onset epileptic encephalopathies (EOEE) and benign seizure disorders. Patients with EOEE suffer from therapy-refractory seizures and a mild to severe developmental delay. Despite the recently discovered large amount of genetic epilepsies due to channelopathies, there is little systematic data on treatment responses.

Material and Methods: To collect data on patients with KCNQ2 related epilepsies and their therapy successes and failures, we searched PubMed. We used the free text term search ‘KCNQ2 AND Epilepsy’ as well as the PubMed Medical Subject Headings (MeSH) search. Based on patients’ clinical information about their therapy, we assigned them to one of four groups: ‘seizure freedom’, ‘responder’, ‘successful therapy’, and ‘unsuccessful therapy’.

Results: From the data of 217 patients, we were able to draw conclusions about individual therapeutic approaches. 84 patients were classified as ‘Early Onset Epileptic Encephalopathy (EOEE)’ whereas 133 patients were classified as ‘benign’. In the ‘EOEE’ group 65.5% of patients were reported seizure free while 14.3% did not respond to treatment. In patients with ‘EOEE’ seizure freedom was more likely achieved when receiving sodium channel blockers. In contrast 92.5% of patients assigned to the ‘benign group’ became seizure free, while 3.8% showed no success to treatment (p = 0.003). Spontaneous seizure remission (without medication) in the ‘benign’ group was achieved in 30.1% of patients. Phenobarbital and sodium channel blockers most often lead to seizure freedom in patients with a ‘benign’ course.

Conclusions: In patients with epilepsies due to a mutation within the potassium channel KCNQ2 seizures are controlled well in the ‘benign’ group and moderately well in the ‘EOEE’ group. In the ‘benign’ group a significant number of seizures stop spontaneously. When considering antiepileptic treatment, phenobarbital should be considered. Sodium channel blockers, e.g. carbamazepine, seem appropriate for both groups, ‘benign’ and ‘EOEE’.