Abstracts

Rationale: Syncope is the most common differential diagnosis of epilepsy. Syncope varies in frequency from one episode in 30% of the population to >4 episodes in 5% of the population. The most frequent type is neurocardiogenic syncope (NCS). However, the etiology remains elusive. Here we provide evidence for a genetic etiology by presenting a large multigenerational family with NCS. Methods: A syncope questionnaire was devised to address features differentiating syncope from epilepsy and administered to all available family members. Relevant medical records were obtained. In selected individuals additional tests (heart rate variability, tilt-table test) were performed. As syncope is common, a scoring system (0-5) was developed to classify the severity of syncope based on the number of syncopal episodes and the circumstances in which they occurred. Those with low scores were considered less likely to have syncope due to the familial disorder (phenocopies). DNA was extracted from peripheral blood in 27 individuals. Linkage analysis using Illumina SNP chips is underway. Results: The family comprises 27 affected individuals over three generations (figure). Seventeen individuals had a score of 4-5 indicating a lower likelihood of being a phenocopy. Two individuals had syncope and epilepsy, and two had epilepsy alone. Segregation indicates an autosomal dominant mode of inheritance with high penetrance for NCS in this family. Age of onset was between 5 and 16 years except for one individual (31 years). Triggers for NCS were venipuncture, pain, prolonged standing, a hot environment, illness and thinking about injuries or medical procedures. Different triggers were relevant in different individuals. Heart rate variability was normal in the 2 individuals tested. Tilt testing was positive in one individual (with isoprenaline) and negative in another individual (without isoprenaline). Conclusions: This is the largest family with autosomal dominant NCS studied and strongly supports a genetic basis for NCS. Identification of the underlying mutation will help to further understanding of the pathophysiology. Funding: NHMRC Australia, Deutsche Forschungsgemeinschaft (KL 2254/1-1 to KMK), The University of Melbourne (KMK)