title: Leber's optic neuropathy: a clinical and visual evoked potential study of affected and asymptomatic members of a six generation family.
abstract: Fourteen clinically affected and 40 asymptomatic members of a six generation family with Leber's optic neuropathy have been studied clinically and by recording pattern-reversal visual evoked potentials. While 12 of the affected members had suffered the typical sequential bilateral failure of vision, in 2 the condition was still monocular after periods of 12 and 14 years. Reduced vascularity of the optic nerve head was found in 11 of these cases, all of whom had some degree of optic atrophy, and showed a significant correlation with the visual acuity. Excessive tortuosity of peripheral retinal vessels was noted in 6 cases and was a prominent feature in the unaffected eye of one of the subjects with monocular visual impairment. In cases with advanced visual impairment the VEP was absent bilaterally, while in those with less severe involvement responses which were delayed, desynchronized and much small than normal could still be recorded. Two subjects with early bilateral clinical involvement had normal or minimally abnormal responses. Repeat studies in 6 subjects after intervals of up to fifteen months showed no change in 4 and a deterioration in 2. It is concluded that the VEP findings in clinically affected subjects are in keeping with a severe demyelinating lesion of the optic nerve with associated nerve fibre loss. Mild impairment of colour vision, pallor or reduced vascularity of the optic nerve head, excessive tortuosity of retinal vessels, a small central scotoma, and/or mild abnormalities or atypical features of the VEP were found in 16 of the 40 asymptomatic family members studied. Such abnormalities were present in 50 per cent of descendants from the female lineage who were at risk of developing the disease, and also in 30 per cent of descendants from male lineages who were not at risk. These findings suggest that there is a stage prior to the onset of visual impairment during which subtle abnormalities may be detected in individuals at risk of developing or transmitting the disease. The finding of asymptomatic abnormalities in descendants from male lineages could be accounted for by transmission of a partial form of the disease by affected or unaffected males, which would be in accord with a cytoplasmic mechanism of transmission for the disease.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D005071:Evoked Potentials; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009896:Optic Atrophy / Q000235:genetics / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000235:genetics / Q000503:physiopathology*; D014786:Vision Disorders / Q000235:genetics / Q000503:physiopathology