Towards Understanding the Genetic Nature of Vasovagal Syncope.

Natalia Matveeva,Olga Favorova,Boris Titov,Elizabeth Bazyleva,Alexander Pevzner

doi:10.3390/ijms221910316

Abstract

Syncope, defined as a transient loss of consciousness caused by transient global cerebral hypoperfusion, affects 30–40% of humans during their lifetime. Vasovagal syncope (VVS) is the most common cause of syncope, the etiology of which is still unclear. This review summarizes data on the genetics of VVS, describing the inheritance pattern of the disorder, candidate gene association studies and genome-wide studies. According to this evidence, VVS is a complex disorder, which can be caused by the interplay between genetic factors, whose contribution varies from monogenic Mendelian inheritance to polygenic inherited predisposition, and external factors affecting the monogenic (resulting in incomplete penetrance) and polygenic syncope types.

Highlights

Syncope, or fainting, is characterized by global cerebral hypoperfusion, transient loss of consciousness with disturbed postural tone, disturbance of the cardiovascular and respiratory systems, and spontaneous recovery back to the normal state [1].A reduction in systemic blood pressure (BP) causing a decrease in cerebral blood flow plays a major role in the pathogenesis of syncope [2]
Taking into account the clinical heterogeneity of VVS and data variation in selected publications on family history, pedigrees, and results of twin studies, it is quite likely that the contribution of environmental factors and the inherited genetic component varies within a broad range
Unlike the “candidate gene” approach when a hypothesis regarding potential involvement of a gene in phenotype is put forward according to its nature and function of the gene product, the genome-wide searching for genes involved in disease/phenotype development employs panels of genetic markers with known chromosomal localization

Summary

Introduction

Fainting, is characterized by global cerebral hypoperfusion, transient loss of consciousness with disturbed postural tone, disturbance of the cardiovascular and respiratory systems, and spontaneous recovery back to the normal state [1]. A surrogate marker, the head-up tilt test (or prolonged passive head up tilt testing) has been used to diagnose VVS since the late 1980s In this test, the patient is moved from the horizontal to vertical position using a special tilting table in order to simulate the neurally mediated reflex and induce syncope. A negative head-up tilt test does not always mean that an individual cannot be diagnosed with neurally mediated syncope. This diagnosis should be suspected in individuals with typical clinical manifestations once all other reasons for transient loss of consciousness have been eliminated. The molecular foundations of VVS pathogenesis can be revealed to develop new strategies for its prevention and management

The Inheritance Pattern of VVS

Candidate Gene Association Studies

Genome-Wide Studies

Findings

Conclusions