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Leber`s hereditary optic neuropathy (LHON) refers to an optic nerve dysfunction due to mutations in the mitochondrial DNA (mtDNA) and is transmitted in a non-mendelian or maternal pattern. However, sporadic forms and singleton cases of LHON are numerous. The prevalence is estimated to 1:50,000. LHON begins generally in young adult patients, with a mean age of onset between 18 and 35 years. Vision loss starts usually in one eye, and is either sudden, leading to acuity lower than 20/400 in less than a week, or progressive over 2 or 3 months. The fellow eye is subsequently affected. Fundus examination often reveals disc pseudooedema and hyperhemia, arteriolar dilatation, vascular tortuosity and peripapillary telangiectasias. Although visual loss is usually the only manifestation, LHON associations with cardiac, neurological or skeletal abnormalities have been reported. The optic atrophy seems to be linked to the respiratory chain dysfuntion caused by mutations in mtDNA. More than 15 mtDNA mutations have been observed in LHON, and at least five correspond to ``primary mutations`` as they are sufficient to induce the disease. The major primary mtDNA mutations involve genes encoding different subunits of the complexes I and III of the mitochondrial respiratory chain. Other mutations, known as ``secondary mutations``, as they are usually associated with primary mutations, might modify the evolution and clinical expression of LHON. Epigenetic or toxic factors could also be involved in the pathogenicity. There is currently no effective treatment for LHON. |