Background: Leber hereditary optic neuropathy (LHON) is associated with primary and secondary mutations in mitochondrial DNA. Clinical studies suggest that there is a wide spectrum of clinical expression.
Methods: Fifty-three affected and 131 unaffected maternal relatives from 21 pedigrees with LHON were studied neuro-ophthalmologically and followed over a period of 14 years. Mitochondrial DNA analysis was performed on their blood specimens.
Results: Thirty-two affected (60%) individuals from ten families harbored the 11778 mutation and ten individuals (19%) from three families harbored the 3460 mutation. No confirmed primary mutation was detected in 11 (21%) affected individuals from eight families. The visual outcome was better in families with the 3460 mutation than in those with the 11778 mutation. Secondary mutations did not affect the penetrance or the visual outcome. Fifteen patients had a favorable outcome; seven of whom had subclinical disease, two had slowly progressive LHON with a favorable visual outcome, and six had classic LHON with spontaneous recovery. In seven patients, the onset of the disease had been in childhood. These patients had a more favorable prognosis than the adults. Results of eye examinations of asymptomatic maternal relatives showed subclinically affected individuals.
Conclusions: In addition to classic LHON, the disease can manifest itself in three different atypical forms: subclinical disease, slowly progressive LHON with a favorable visual outcome, and LHON with the classic acute stage but spontaneous visual recovery. The current study suggests that the ophthalmologic findings and outcome in LHON are independent of secondary mutations.