Volume.126 Number.1

Original article : Clinical science

Clinical and Genetic Characteristics of Japanese Patients with Enhanced S-cone Syndrome
Takaaki Hayashi1,2, Kei Mizobuchi1, Shuhei Kameya3, Kazuki Kuniyoshi4, Shunji Kusaka4, Shinji Ueno5, Koji M. Nishiguchi5, Yozo Miyake6, Tadashi Nakano1
1 Department of Ophthalmology, The Jikei University School of Medicine
2 Department of Ophthalmology, The Jikei University School of Medicine, Katsushika Medical Center
3 Department of Ophthalmology, Chiba Hokuso Hospital, Nippon Medical School
4 Department of Ophthalmology, Kindai University Faculty of Medicine
5 Department of Ophthalmology, Nagoya University Graduate School of Medicine
6 Kobe Eye Center, Next Vision

Purpose: Enhanced S-cone syndrome (ESCS) is an inherited retinal disease that exhibits an increased short-wavelength-sensitive(s)-cone response in the electroretinogram (ERG). Whether ESCS is a progressive disorder of the retinal function or not remains unclear. Herein we retrospectively investigate the longitudinal clinical course, including electroretinography (ERG) and genetic features, of Japanese ESCS cases.
Subjects and methods: In this study, we examined nine patients diagnosed with ESCS; early clinical features in eight patients have been previously reported. Mutation analysis of the NR2E3 gene was performed by Sanger sequencing. We assessed visual acuity, central foveal thickness (CFT) using optical coherence tomography, and ERG findings.
Results: Seven patients whose initial symptoms could be identified were aware of night blindness before school age. The mean age was 36.2 years at the first ophthalmological evaluation visit, and the mean follow-up period was 15.0 years. Visual acuity of the worse-seeing eye did not change significantly during follow-up. The CFT at the final measurement was significantly reduced compared with that at the first measurement. All patients exhibited characteristic findings in both full-field and S-cone ERG. In two patients who could be followed up for a long period of >20 years, the amplitude responses were clearly reduced. Biallelic NR2E3 mutations were found in all patients, and the p. Arg104Gln was the most frequently found mutation in this study (28%; 5/18 alleles).
Conclusions: The ERG findings indicate that ESCS is a progressive degenerative retinal disease. Visual acuity may be relatively stable for a long time unless ESCS patients develop macular retinoschisis. The p. Arg104Gln was considered as the main mutation in Japanese patients with ESCS.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 126: 7-18, 2022.

Key words
Inherited retinal disease, Electroretinogram, NR2E3 gene, Autosomal recessive inheritance, Macular retinoschisis
Reprint requests to
Takaaki Hayashi, M. D. Department of Ophthalmology, The Jikei University School of Medicine, Katsushika Medical Center. 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan