Objective: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease that causes bilateral central visual loss, predominantly in young men. Recently, this disorder has been associated with point mutations in the mitochondrial genome. The clinical characteristics of LHON are reviewed with special attention to recent advances in mitochondrial genetics.
Data sources: Literature from the mid-19th century to the present is reviewed.
Study selection: Major review articles that include multiple large pedigrees in their analysis are featured. Special emphasis is placed on the recent reports on mitochondrial DNA abnormalities associated with this disease.
Data extraction: The older literature is reviewed critically with an understanding that some of the patients included as examples of LHON may have had a different disease. The more current references are assessed in regard to their inclusion of appropriate and complete mitochondrial DNA analysis.
Data synthesis: Leber's hereditary optic neuropathy, a maternally inherited disease primarily of young men, results in bilateral, acute or subacute, central visual loss and, ultimately, optic atrophy. Point mutations in the mitochondrial genes encoding proteins essential to oxidative phosphorylation have been associated with this disorder. Primary mutations include those found at positions 11778, 3460, and, possibly, 15257 and 14484. Mitochondrial, nuclear, and environmental factors may modify phenotypic expression.
Conclusion: Genetic analysis has allowed for a broader view of what constitutes the clinical phenotype of LHON.