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Genotypic and phenotypic characteristics of Korean children with childhood-onset Leber’s hereditary optic neuropathy

  • Neurophthalmology
  • Published:
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Abstract

Purpose

We sought to identify the phenotypic and genotypic characteristics of Korean children with genetically confirmed Leber’s hereditary optic neuropathy (LHON).

Methods

The medical records of 64 genetically confirmed LHON patients were reviewed. Seventeen patients aged 13 years or younger with optic atrophy with positive mitochondrial DNA (mtDNA) mutations were considered to demonstrate childhood-onset LHON. The non-childhood-onset group included 47 patients with genetically confirmed LHON who experienced disease onset later than 13 years of age. The type of mtDNA mutation, visual acuity (VA), color vision, fundus photography, retinal nerve fiber layer (RNFL) thickness, and visual field were investigated.

Results

Sequence analysis of the mitochondrial genome revealed five different kinds of LHON-associated mtDNA mutations among our childhood-onset patients, including m.11778G>A (58.8%), m.3496G>T (11.8%), m.3497C>T (5.9%), m.11696G>A (5.9%), and m.14502T>C (5.9%). The mean final best-corrected VA in the childhood-onset group was better than that in the non-childhood-onset group with the value of logMAR 0.29 (0.09–0.75) vs. 0.55 (0.27–1.29) (expressed as median (interquartile range); p = 0.05). Spontaneous visual recovery was observed in 35.3% of the childhood-onset group but in only 12.8% of the non-childhood-onset group (p = 0.04). Eight patients (47.1%) showed interocular asymmetry of the disease, with two presenting true unilateral involvement of the optic nerve and the other six patients demonstrating unilateral subclinical manifestations with bilateral optic atrophy.

Conclusion

Involvement of secondary mitochondrial mutations was confirmed in patients with childhood-onset LHON. Characteristic clinical features of childhood-onset LHON included a higher proportion of subacute or insidious onset of symptoms, better VA, higher spontaneous recovery, and asymmetrical ocular involvement.

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Acknowledgments

We would like to thank Dr. Yong-Gyu Park, a specialist in biostatistics, for his detailed and professional statistical advice in this study.

Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science, ICT & Future Planning (NRF-2016R1C1B1016590). Also, the authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2019.

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Author notes

  1. Ye Jin Ahn and Yooyeon Park contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea

    Ye Jin Ahn, Yooyeon Park, Sun Young Shin & Shin Hae Park

  2. Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea

    Hyojin Chae & Myungshin Kim

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  1. Ye Jin Ahn
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All authors were responsible for and/or involved in the provision of patients/data acquisition, data analysis, data review, and interpretation. All authors reviewed the manuscript and approved the final version for submission.

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Correspondence to Shin Hae Park.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board of Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants or their guardians if the participants were younger than 14 years of age included in the study.

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Ahn, Y.J., Park, Y., Shin, S.Y. et al. Genotypic and phenotypic characteristics of Korean children with childhood-onset Leber’s hereditary optic neuropathy. Graefes Arch Clin Exp Ophthalmol 258, 2283–2290 (2020). https://doi.org/10.1007/s00417-020-04757-x

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