Mitochondrial DNA diseases: genotype and phenotype in Leber's hereditary optic neuropathy

We have investigated 107 patients from 79 families with Leber's hereditary optic neuropathy (LHON), defined by the presence of one of the mitochondrial DNA (mtDNA) mutations at positions 11778 (60 families), 3460 (7), or 14484 (12). Only about 60% of the index patients had a history of similarly affected relatives. The ratios of affected male:female patients were 2.5:1 (11778), 2:1 (3460), and 5.7:1 (14484). Visual loss developed between the ages of 11 and 30 years in 69% with a range of 6-62 years, and this was not significantly different between mutation groups or males and females. Retinal microangiopathy was not detected in 36% of patients examined within 3 months of visual loss. A multiple sclerosis-like illness occurred in 45% of females with the 11778 mutation. Prognosis was better in the 14484 than the 3460 or 11778 patients, with useful recovery in 71% of patients. Good visual outcome was positively correlated with early age of onset (before 20 years). Unusual presentations, including young or old age at onset, caused diagnostic difficulties in this series, usually in the absence of a family history, which were resolved by mtDNA analysis. Recurrence risks to relatives could be derived from this series of families with genetically defined LHON.