Identical twins who are discordant for Leber's hereditary optic neuropathy
D. R. Johns, K. H. Smith, N. R. Miller, M. E. Sulewski and W. B. Bias
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Md.
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, co-existent 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 1/2 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.
