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August 07, 2012; 79 (6) Articles

Evidence for genetic factors in vasovagal syncope

A twin-family study

Karl Martin Klein, San San Xu, Kate Lawrence, Alexandra Fischer, Samuel F. Berkovic
First published August 6, 2012, DOI: https://doi.org/10.1212/WNL.0b013e3182635789
Karl Martin Klein
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San San Xu
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Kate Lawrence
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Alexandra Fischer
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Samuel F. Berkovic
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Citation
Evidence for genetic factors in vasovagal syncope
A twin-family study
Karl Martin Klein, San San Xu, Kate Lawrence, Alexandra Fischer, Samuel F. Berkovic
Neurology Aug 2012, 79 (6) 561-565; DOI: 10.1212/WNL.0b013e3182635789

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Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

GLOSSARY

ATR=
Australian Twin Registry;
DZ=
dizygous;
MZ=
monozygous;
VVS=
vasovagal syncope

Footnotes

  • Study funding: Supported by a project grant (ID 509135) and an enabling grant (ID 628911) of the National Health and Medical Research Council of Australia. K.M.K. was supported by a research fellowship from the Deutsche Forschungsgemeinschaft (KL 2254/1-1) and a scholarship from The University of Melbourne.

  • Supplemental data at www.neurology.org

  • Received January 19, 2012.
  • Accepted March 19, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.
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