In contrast to the ameliorating effect of Cacna1g on the mouse model of Dravet syndrome, CACNA1A has a worsening effect on Dravet syndrome, meaning subjects carrying both SCN1A and CACNA1A variants develop absence seizures earlier and more frequently than patients with only SCN1A mutations [83]. Here, CACNA1A is linked to encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy.