Abstracts

Mutations of ion channel genes are recognized as an important cause of defined inherited syndromes in epilepsy and cardiac arrhythmias. We are reporting preliminary data on the following; (1) the prevalence of cardiac co-morbidities and (2) the frequency and spectrum of genetic variation in the five major genes associated with long QT syndrome in patients with idiopathic epilepsies (IE)., 153 patients with IE were systematically recruited and detailed phenotypic data regarding epilepsy and cardiac arrhythmias were collected. DNA samples were analyzed by sequencing across five major LQT genes ([italic]SCN5A, KCNQ1, KCNH2, KCNE1, [/italic]and[italic] KCNE2[/italic])., Routine ECG was performed in 41/153 individuals. The study was abnormal in 13/41 (32%) subjects. 9/41 (22%) patients had both an abnormal ECG and a medical history positive for syncope, cardiac palpitations or skipped beats. 2/153 (4%) patients were lost due to sudden unexplained death in epilepsy (SUDEP) within one year of follow-up. Interim DNA sequence analysis of the five major LQT genes in the IE population showed that 27% of all the LQT single nucleotide polymorphisms (SNPs) were exon bound variants of which 45% was represented by protein altering/non-synonymous SNPs (NS-SNPs). NS-SNPs were most commonly found in the [italic]SCN5A[/italic] (33%) and [italic]KCNH2[/italic] (43%) genes. [italic]SCN5A [/italic]and[italic] KCNH2[/italic] NS-SNPs were also the most frequent genetic variants found in patients with dual phenotype of cardiac arrhythmias and epilepsy., The prevalence of inter-ictal cardiac arrhythmias in our cohort of idiopathic epilepsy patients was similar to the prevalence of ictal arrhythmias cited in the literature [(39%) by Nei et al.Epilepsia.2004;45(4):338-345, and (35%) by Opherk et al. Epilepsy Res.2002;52(2):117-27]. The presence of relatively frequent non-synonymous coding variants in the [italic]SCN5A[/italic] and [italic]KCNH2[/italic] genes in IE patients with a cardiac phenotype suggests their involvement in the comorbid dual clinical phenotype of cardiac arrhythmias and seizures., (Supported by NINDS 5K08NS47304-3 and NS049130.)