Genetic Insights into Vasovagal Syncope

Introduction: Vasovagal syncope (VVS) is the most frequent type of syncope and affects about 25% of the population. The role of genetic factors in VVS has long been debated. In this talk the current evidence suggesting a strong genetic component will be presented. Clinical genetic studies: Multiple family aggregation studies have shown that individuals with VVS are more likely to have affected family members with VVS than unaffected controls. A twin study showed significantly higher concordance rates in monozygous compared to dizygous twins for frequent syncope and syncope associated with typical vasovagal triggers. This provides clear evidence for the relevance of genetic factors. Analysis of the family history of the concordant monozygous twins revealed that VVS most frequently follows complex inheritance but rarer families with autosomal dominant inheritance also exist. Several autosomal dominant families have been described in the literature with the largest including 30 affected individuals. Molecular genetic studies: Candidate gene association studies have so far revealed either negative or unconfirmed results. However, in an autosomal dominant family the first locus for VVS was identified on chromosome 15q26. The underlying gene has not been identified yet. Conclusion: Genetic factors are relevant in VVS. Complex inheritance is operative in the majority of cases. Autosomal dominant inheritance occurs less frequently. Identification of the underlying genes will improve our understanding of pathophysiology and may lead to new therapeutic strategies.