While the haploinsufficiency of genes located near the telomere, such as PIGG, CPLX1, CTBP1, and LETM1, has been traditionally implicated in seizure susceptibility [6,8,9], our data suggest that the most severe, drug-resistant forms of epilepsy may be associated with larger deletions extending proximally to around 8–11 Mb on chromosome-4p. Here, CPLX1 is linked to epilepsy.