Evidence for genetic factors in vasovagal syncope: a twin-family study

Vasovagal syncope (VVS) is the most frequent type of syncope and a common differential diagnosis of epilepsy. The role of genetic factors in VVS is debated. We performed a twin-family study to clarify this question and to analyze the putative mode of inheritance.

Fifty-one same-sex twin pairs where at least 1 had syncope were ascertained. The twins were interviewed via telephone using a standardized questionnaire. Available medical records were obtained. Information on the affected status of first- and second-degree relatives was acquired.

There was a trend toward higher casewise concordance in monozygous (MZ, 0.75) than dizygous (DZ, 0.50) twins for any syncope (p = 0.06). Significant and strong effects on concordance between MZ and DZ twins were found for fainting at least twice unrelated to external circumstances (0.71 vs 0.27, p = 0.018) and for syncope associated with typical vasovagal triggers (0.62 vs 0.00, p < 0.001). Twelve of 19 concordant MZ twin pairs reported sparse or no other affected family members whereas in the other 7 pairs multiple close relatives were affected.

The twin analysis provides strong evidence for the relevance of genetic factors in VVS. Analysis of the families suggests that complex inheritance (multiple genes ± environmental factors) is usual, with rarer families possibly segregating a major autosomal dominant gene.