Abstracts

Rationale: Calcium channel (CACNA) mutations affect multiple organ systems and most notably cause epilepsy, migraine, and movement disorders. Little has been reported on the phenotypic variation in epilepsy with CACNA mutations other than the association of CACNA1H with childhood absence epilepsy. Methods: Review of institutional experience with drug-resistant epilepsy patients carrying CACNA1 mutations. Our review uncovered 12 patients – four with mutation in CACNA1A, three in 1H, two in 1B, 1 in 1S and two in 1H and 1A mutations. Results: Of the CACNA1A patients, average age of epilepsy onset was 3 years. Three had generalized epilepsy with normal MRI (2) or with decreased myelination (1). One patient had focal epilepsy with mesial temporal sclerosis on MRI. The two patients with abnormal MRI were severely delayed with poor functional status, the other two performed in school with individualized education plans. (IEP). All CACNA1A patients had background slowing on EEG. Only the patient with focal epilepsy experienced status epilepticus. Of the two patients with CACNA1B mutations, average age of epilepsy onset was nearly 3 years. One had generalized epilepsy with multiple seizure types, generalized discharges on EEG but normal background and normal MRI. He also had autism spectrum disorder and required IEP. There was no history of status epilepticus. The other 1B patient had focal epilepsy with periventricular nodular heterotopia and Lennox Gastaut syndrome, a history of status epilepticus and was severely delayed - nonverbal and nonambulatory. Of 3 1H patients, all had generalized epilepsy with age of onset ranging 8 months to 4 years. One with only absence seizures had normal EEG background, MRI and development. The other two also carried SCN1A mutations and had febrile seizures and multiple seizure types. One had EEG background slowing and moderate intellectual disability; the other had normal background but required an IEP. Two patients carried both 1A and 1H mutations. Both had focal EEG discharges and background slowing on EEG with multiple seizure types. One patient with delayed myelination on MRI had minimal language development and history of status epilepticus. The other had normal MRI and no status epilepticus but required IEP. The one 1S patient had IGE with age of onset 6 years, normal IQ and normal EEG background. In summary, of the patients identified with calcium channel mutations and drug resistant epilepsy, the most common seizure type was absence (75% of patients), 25% had focal discharges on EEG and focal epilepsy while the others had generalized discharges, 67% had EEG background slowing and 67% had normal MRI. 33% had experienced status epilepticus. Average delay in genetic diagnosis after epilepsy onset was 4.7 years. Average length of follow was 5 years. Conclusions: Voltage gated calcium channels are involved in epilepsy, most notably childhood absence epilepsy. Our data suggest that the phenotypic spectrum of calcium channel-associated epilepsy may be broader and more severe than previously described. Funding: Gerlach Endowment