Genetics of vasovagal syncope

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 review we will discuss the current evidence that strongly suggests a major genetic component.

Family aggregation studies have consistently shown that individuals with VVS more frequently have affected family members with VVS than unaffected controls. Clear evidence for the relevance of genetic factors was provided by a twin study that showed significantly higher concordance rates in monozygous compared to dizygous twins for frequent syncope and syncope associated with typical vasovagal triggers. Analysis of the family history of the concordant monozygous twins revealed that complex inheritance is operative in the majority 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.

Candidate gene association studies have so far been disappointing as they have 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.

Genetic factors play a role in VVS. Most cases follow complex inheritance; autosomal dominant inheritance occurs less frequently. Identification of the underlying genes will improve our understanding of pathophysiology and may lead to new therapeutic strategies.