Leber's hereditary optic neuropathy

Keywords Disease name and synonyms Excluded diseases Definition/Diagnosis criteria Differential diagnosis Frequency Clinical description Etiology Paraclinic testing and diagnosis Treatment References Abstract 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 can be affected, either almost simultaneously in nearly 50 % of the patients, or sequentially with sometimes an interval as long as 9 months. 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 dysfunction caused by mutations in mtDNA. More than 18 mtDNA mutations have been observed in LHON, and at least four 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'', are usually associated with primary mutations. Epigenetic or toxic factors could also be involved in the pathogenicity. There is currently no effective treatment for LHON.