Given that five APEs with a mean seizure onset age of 44.2 years (range: 32–55 years) in whom possible genetic causes were identified had definitely acquired etiologies prior to seizure onset, including traumatic brain tissue loss or encephalitis, it is plausible that one variant of the relevant genes (SCN1A, TSC1, ADGRV1, EFHC1 and PRICKLE1) alone may not be sufficient to cause the relevant epilepsies in the absence of acquired brain damage. This evidence concerns the gene SCN1A and epilepsy.