Impaired Color Recognition in HCN1 Epilepsy: A Single Case Report

Chaseley E Mckenzie; Chen-Jui Ho; Ian C Forster; Ming S Soh; A Marie Phillips; Ying-Chao Chang; Ingrid E Scheffer; Christopher A Reid; Meng-Han Tsai

doi:10.3389/fneur.2022.834252

Impaired Color Recognition in HCN1 Epilepsy: A Single Case Report

Front Neurol. 2022 Mar 10:13:834252. doi: 10.3389/fneur.2022.834252. eCollection 2022.

Authors

Chaseley E Mckenzie¹, Chen-Jui Ho², Ian C Forster¹, Ming S Soh¹, A Marie Phillips^{1

3}, Ying-Chao Chang⁴, Ingrid E Scheffer^{1

5

6}, Christopher A Reid^{1

5}, Meng-Han Tsai^{2

7

8}

Affiliations

¹ Early Development Division, Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
² Division of Epilepsy, Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
³ School of Biosciences, The University of Melbourne, Parkville, VIC, Australia.
⁴ Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁵ Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.
⁶ Department of Paediatrics, Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, VIC, Australia.
⁷ School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁸ Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Abstract

Variants in HCN1 are associated with a range of epilepsy syndromes including developmental and epileptic encephalopathies. Here we describe a child harboring a novel de novo HCN1 variant, E246A, in a child with epilepsy and mild developmental delay. By parental report, the child had difficulty in discriminating between colors implicating a visual deficit. This interesting observation may relate to the high expression of HCN1 channels in rod and cone photoreceptors where they play an integral role in shaping the light response. Functional analysis of the HCN1 E246A variant revealed a right shift in the voltage dependence of activation and slowing of the rates of activation and deactivation. The changes in the biophysical properties are consistent with a gain-of-function supporting the role of HCN1 E246A in disease causation. This case suggests that visual function, including color discrimination, should be carefully monitored in patients with diseases due to HCN1 pathogenic variants.

Keywords: HCN1; color vision; developmental and epileptic encephalopathy; epilepsy; missense.