CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited mutations, with median age of 2,5 years at epilepsy onset. Eight were novel. Two variants known leading to gain function (GOF) found 5 patients. Five other had non-sense loss (LOF). Seizures most often revealed by either status epilepticus (SE) (n = 8), eventually triggered fever 5), absences/behavioural arrests 7). Non-epileptic paroxysmal events frequent consisted recurrent accesses 9), jitteriness the neonatal period 6), ocular 9). Most early permanent cerebellar dysfunction 16) moderate severe global developmental delay (GDD)/intellectual deficiency (ID) 17). MRI was abnormal, 8) and/or cerebral 6) atrophy. Stroke-like occurred 2 cases. Some antiepileptic drugs topiramate, levetiracetam, lamotrigine valproate effective on seizures. Acetazolamide calcium channel blockers when used. More than half refractory epilepsy. mutation should be evoked front main electro-clinical that associated GDD/ID. The first one, all GOF variants, characterized intractable seizures, SE accesses. second, less severe, LOF onset absence