SUDEP risk and autonomic dysfunction in genetic epilepsies

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.