Abstract
Background: Leber hereditary optic neuropathy (LHON) is a cause of inherited blindness that typically presents with bilateral, painless, subacute visual failure in young adult males. Males are about four times more likely to be affected than females and 95% of LHON carriers become affected before the age of 50. Affected patients may have characteristic ocular fundal appearances and have evidence of optic nerve dysfunction in the form of impaired colour vision (dyschromatopsia), dense visual field defects (central or caecocentral scotoma) and abnormal visual electrophysiology. Objectives: To summarise the current clinical approach to the molecular diagnosis and clinical management of LHON. Methods: To review the literature and present a review of current understanding. Results/conclusions: The diagnosis of LHON is usually confirmed by molecular genetic analysis for one of three common mitochondrial DNA (mtDNA) mutations that all affect genes coding for complex I subunits of the respiratory chain: m.3460G > A, m.11778G > A and m.14484T > C. Sequencing of the entire mitochondrial genome can reveal the underlying cause in the minority of patients (∼ 5%) who do not harbour one of these three primary mutations, but a molecular diagnosis is not always possible. A minority of LHON patients exhibit a more widespread multi-system involvement with extra neurological features such as dystonia or a multiple sclerosis-like illness. Management is largely supportive, with the provision of low-vision aids, registration with the relevant social services and an important role for genetic counselling.