SUDEP risk and autonomic dysfunction in genetic epilepsies

Ahmed N Sahly; Michael Shevell; Lynette G Sadleir; Kenneth A Myers

doi:10.1016/j.autneu.2021.102907

SUDEP risk and autonomic dysfunction in genetic epilepsies

Auton Neurosci. 2022 Jan:237:102907. doi: 10.1016/j.autneu.2021.102907. Epub 2021 Nov 10.

Authors

Ahmed N Sahly¹, Michael Shevell², Lynette G Sadleir³, Kenneth A Myers⁴

Affiliations

¹ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.
² Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute of the McGill University Medical Centre, Montreal, Quebec, Canada.
³ Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
⁴ Division of Neurology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute of the McGill University Medical Centre, Montreal, Quebec, Canada. Electronic address: kenneth.myers@mcgill.ca.

PMID: 34773737
DOI: 10.1016/j.autneu.2021.102907

Abstract

The underlying pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains unclear. This phenomenon is likely multifactorial, and there is considerable evidence that genetic factors play a role. There are certain genetic causes of epilepsy in which the risk of SUDEP appears to be increased relative to epilepsy overall. For individuals with pathogenic variants in genes including SCN1A, SCN1B, SCN8A, SCN2A, GNB5, KCNA1 and DEPDC5, there are varying degrees of evidence to suggest an increased risk for sudden death. Why the risk for sudden death is higher is not completely clear; however, in many cases pathogenic variants in these genes are also associated with autonomic dysfunction, which is hypothesized as a contributing factor to SUDEP. We review the evidence for increased SUDEP risk for patients with epilepsy due to pathogenic variants in these genes, and also discuss what is known about autonomic dysfunction in these contexts.

Keywords: Autonomic dysfunction; Genetic epilepsy; Heart rate variability; SUDEP.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Autonomic Nervous System Diseases*
Death, Sudden
Epilepsy* / genetics
Humans
Risk Factors
Sudden Unexpected Death in Epilepsy*