Abstracts

Rationale: To expand the phenotypic spectrum of CACNA1H mutations and describe potential co-morbid conditions Methods: The phenotypic spectrum of five patients with de novo pathogenic CACNA1H mutations was explored. Included features were: age of seizure onset, seizure semiology, response to therapy, brain imaging findings, EEG characteristics, behavior, and co-morbid conditions Results: All patients had de novo pathogenic heterozygous mutations in CACNA1H. The mean age of seizure onset was 8 years. Seizure semiology varied with patients experiencing absence, complex-partial, myoclonic, atonic, and generalized tonic-clonic events. EEGs showed focal, multifocal or generalized discharges. One child had global developmental delay with autism and one had developmental regression following seizure onset. Two patients had failure to thrive and functional B-cell immunodeficiency Conclusions: CACNA1H encodes for the a1H subunit of Cav3.2 channels, a subtype of T-type channels expressed at neuronal cell bodies and dendrites. CACNA1H mutations have previously been associated with susceptibility to idiopathic generalized epilepsy. Our series demonstrates that patients are susceptible to focal onset epilepsy as well. Phenotype varied from mild to intractable with fifty percent of our patients responding to anti-epileptic medication. Two patients required VNS placement and one required a ketogenic diet. The recognition of immunodeficiency in two patients may represent a co-morbidity that has not previously been recognized. Both patients with functional B-cell deficiency responded well to immunoglobulin therapy. Larger studies are required to delineate further the phenotypic characteristics and to determine if functional B-cell deficiency is part of the spectrum of CACNA1H mutations. Funding: None