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Genetics and SUDEP: Challenges and Future Directions.

Robyn Whitney¹, Suvasini Sharma², Kevin C Jones¹

¹Division of Neurology, Department of Paediatrics, McMaster University, Hamilton, Ontario, Canada.

|July 6, 2023

Summary

This summary is machine-generated.

Sudden unexpected death in epilepsy (SUDEP) is a major concern, with genetic factors increasingly implicated. Understanding these genetic risks, including polygenic effects, is crucial for prevention strategies.

Keywords:

SUDEP developmental and epileptic encephalopathy epilepsy genetics molecular autopsy

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Area of Science:

Neurology
Genetics
Epilepsy Research

Background:

Sudden unexpected death in epilepsy (SUDEP) is the primary cause of epilepsy-related mortality in both children and adults.
The pathophysiology of SUDEP remains largely unknown, despite its significant impact.
Tonic-clonic seizures are the most significant risk factor for SUDEP.

Purpose of the Study:

To review the current understanding of genetic contributions to SUDEP.
To discuss the challenges and future directions in genetic testing for SUDEP.
To explore the role of genetic variants, including polygenic risk, in SUDEP.

Main Methods:

Review of current literature on SUDEP genetics.
Analysis of findings from post-mortem molecular autopsies in SUDEP cases.
Discussion of genetic testing methodologies and challenges.

Main Results:

Pathogenic variants in epilepsy and cardiac genes are identified in some SUDEP cases.
Developmental and epileptic encephalopathies (DEEs) are associated with increased SUDEP risk.
Polygenic risk is a postulated factor, though mechanisms are complex.

Conclusions:

Genetic factors play a role in SUDEP, necessitating further research.
Molecular autopsy is underutilized in SUDEP cases due to interpretation, cost, and availability challenges.
Future research should focus on elucidating genetic mechanisms and improving post-mortem genetic testing.