IDENTICAL-TWINS WHO ARE DISCORDANT FOR LEBER HEREDITARY OPTIC NEUROPATHY

Objective: Leber's hereditary optic neuropathy is a maternally inherit ed form of visual loss that is associated with several mitochondrial D NA mutations. These mitochondrial DNA mutations are not the sole deter minants of visual loss, as epigenetic factors may play a pathogenetic role. To clarify the role of these factors, we studied two visually di scordant twins and determined their zygosity and mitochondrial genotyp e. 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 f ields (measured with static and dynamic perimetry) and color vision, a nd results of funduscopic examination; alcohol and tobacco use, head t rauma, coexistent medical illness, and occupational exposure; and resu lts of mitochondrial DNA analysis and determination of zygosity. Resul ts: The monozygous twin brothers have remained discordant for the deve lopment of optic neuropathy for 6 1/2 years despite harboring the iden tical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations. Conclusions: The patients are visually discordant despite being geneti cally identical at the nuclear and mitochondrial levels. Epigenetic fa ctors are important determinants of visual loss in Leber's hereditary optic neuropathy in these brothers. Among those factors studied in the se patients, a substantial difference was noted in regard to occupatio nal exposure to toxic substances. Epigenetic factors that may influenc e the clinical expression of the mitochondrial DNA mutations associate d with Leber's hereditary optic neuropathy should be systematically st udied. Risk-factor intervention strategies should be formulated and im plemented.