The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation.

One hundred and seven patients from 79 families were defined as having Leber's hereditary optic neuropathy (LHON) by the presence of one of the mitochondrial DNA (mtDNA) mutations at positions 11778 (60 families), 3460 (seven families) or 14484 (12 families). Only half of the 11778 index patients had a history of similarly affected relatives; this proportion was higher with the 3460 (71%) and 14484 (100%) mutations. The ratios of affected male to female patients were 2.5:1 (11778), 2:1 (3460), and 5.7:1 (14484). Detailed clinical data were available for 79 patients from 55 families. Visual loss developed between the ages of 11 and 30 years in 69%, with a range of 6-62 years, and no significant differences between mutation groups or males and females. It was bilateral in all but two patients, to a median of counting fingers with a central scotoma, developing simultaneously in 22% and sequentially in 78%, with a median inter-eye delay of 8 weeks, and progressing in each eye over a period of 4-6 weeks. Nineteen patients had pain in an affected eye or on eye movements, and four experienced Uhthoff's phenomenon. Retinal microangiopathy was uncommon after 6 months from onset and was not detected in 36% of patients examined within 3 months of visual loss; the microangiopathy was particularly uncommon in the 14484 group. There was no difference in the overall visual outcome between the 11778 and 3460 groups with median final visual acuities of 1/60 and 3/60, respectively. Particularly severe visual loss occurred in one-third of women with the 11778 mutation, to vague perception of light or no perception of light in at least one eye. A multiple sclerosis-like illness was observed in 45% of females with the 11778 mutation. Prognosis was substantially better in the 14484 patients, with recovery to a final visual acuity of at least 6/24, in 71% of patients. Good visual outcome was strongly correlated with age at onset, all those with onset before 20 years having a final visual acuity better than 6/24 as opposed to only 2 out of 6 with later onset. Improvement in vision occurred as long as 4 years after onset. High alcohol and tobacco consumption, cranial or ocular trauma, young or old age at presentation, co-existing neurological disease, and recent childbirth with post-partum haemorrhage, all contributed to diagnostic difficulties in this series, usually in the absence of a family history. These problems were resolved by mtDNA analysis.