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Donald R. Johns, MD; Kyle H. Smith, MD; Neil R. Miller, MD; Michael E. Sulewski, MD; Wilma B. Bias, PhD

Arch Ophthalmol. 1993;111(11):1491-1494.

Abstract
Objective
Leber's hereditary optic neuropathy is a maternally inherited form of visual loss that is associated with several mitochondrial DNA mutations. These mitochondrial DNA mutations are not the sole determinants of visual loss, as epigenetic factors may play a pathogenetic role. To clarify the role of these factors, we studied two visually discordant twins and determined their zygosity and mitochondrial genotype.

Design
Case series.

Setting
Referral center.

Patients
Identical twin brothers from a family with the 11778 mitochondrial DNA mutation.

Main Outcome Measures
Visual acuity, results of testing for visual fields (measured with static and dynamic perimetry) and color vision, and results of funduscopic examination; alcohol and tobacco use, head trauma, coexistent medical illness, and occupational exposure; and results of mitochondrial DNA analysis and determination of zygosity.

Results
The monozygous twin brothers have remained discordant for the development of optic neuropathy for 6 years despite harboring the identical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations.

Conclusions
The patients are visually discordant despite being genetically identical at the nuclear and mitochondrial levels. Epigenetic factors are important determinants of visual loss in Leber's hereditary optic neuropathy in these brothers. Among those factors studied in these patients, a substantial difference was noted in regard to occupational exposure to toxic substances. Epigenetic factors that may influence the clinical expression of the mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy should be systematically studied. Risk-factor intervention strategies should be formulated and implemented.

Author Affiliations
From the Departments of Neurology (Drs Johns and Miller), Medicine (Dr Bias), and Ophthalmology (Dr Miller) and The Wilmer Ophthalmological Institute (Dr Miller), The Johns Hopkins University School of Medicine, Baltimore, Md; the Division of Ophthalmology, Scott and White Clinic, Temple, Tex (Dr Smith); and the Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia (Dr Sulewski). Dr Johns is now with Beth Israel Hospital, Harvard Medical School, Boston, Mass.

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