CHD2 variants are a risk factor for photosensitivity in epilepsy

Area of Science:

• Genetics
• Neuroscience
• Epilepsy Research

Background:

• Photosensitivity, an abnormal cortical response to flickering light, is linked to specific electroencephalographic changes and can occur with or without seizures.
• While photosensitivity is a known feature of rare epileptic encephalopathies caused by de novo CHD2 mutations, its role in common epilepsies remains unclear.

Purpose of the Study:

• To investigate the association between CHD2 gene variations and photosensitivity in various epilepsy types, including common epilepsies, specific photosensitive epilepsies, and individuals with photosensitivity but no seizures.
• To determine if unique CHD2 variants contribute to photosensitivity in epilepsy.

Main Methods:

• Analyzed CHD2 gene sequences from 580 individuals with photosensitive epilepsy and 55 individuals with photoparoxysmal response but no seizures.
• Compared case data with CHD2 sequence data from 34,427 controls, focusing on unique variants.
• Utilized zebrafish larvae models to assess the impact of chd2 knockdown on photosensitivity.

Main Results:

• Unique CHD2 variations were significantly over-represented in individuals with photosensitive epilepsies compared to controls (P = 2.17 × 10(-5)).
• A notable over-representation of unique CHD2 variants was found in eyelid myoclonia with absences, an archetypal photosensitive epilepsy syndrome (P = 3.50 × 10(-4)).
• CHD2 variation was not over-represented in individuals with photoparoxysmal response but no seizures. Zebrafish larvae with reduced chd2 function exhibited enhanced photosensitivity.

Conclusions:

• CHD2 mutations are identified as a cause of eyelid myoclonia with absences, the archetypal generalized photosensitive epilepsy syndrome.
• Unique CHD2 variants are associated with photosensitivity in common epilepsies.
• The findings suggest CHD2's role in human cortical excitability, independent of ion channel function, opening new research directions.