Impaired Color Recognition in HCN1 Epilepsy: A Single Case Report

Area of Science:

• Neuroscience
• Genetics
• Ophthalmology

Background:

• Pathogenic variants in the HCN1 gene are associated with various epilepsy syndromes, including developmental and epileptic encephalopathies.
• HCN1 channels are highly expressed in retinal photoreceptors, suggesting a role in visual function.

Purpose of the Study:

• To report a novel de novo HCN1 variant (E246A) in a child with epilepsy and developmental delay.
• To investigate the functional consequences of the HCN1 E246A variant.
• To explore the potential link between HCN1 variants and visual deficits, specifically color discrimination.

Main Methods:

• Clinical case description of a child with epilepsy and mild developmental delay.
• Parental report of visual deficits, including color discrimination difficulties.
• In vitro functional analysis of the HCN1 E246A variant's biophysical properties.

Main Results:

• A novel de novo HCN1 variant, E246A, was identified in the patient.
• Functional analysis revealed a gain-of-function effect for the E246A variant, characterized by a right shift in voltage dependence of activation and slowed activation/deactivation rates.
• The patient exhibited difficulties with color discrimination, suggesting a visual deficit.

Conclusions:

• The HCN1 E246A variant's gain-of-function properties support its role in disease causation.
• This case suggests a potential link between HCN1 pathogenic variants and visual dysfunction, including impaired color discrimination.
• Ophthalmological monitoring, particularly for color vision, is recommended for patients with HCN1-related disorders.