Familial non-arteritic anterior ischemic optic neuropathy

Purpose Primary objective was to investigate clinical characteristics of nonarteritic anterior ischemic optic neuropathy (NA-AION) in three families; secondarily, to test these families for a previously detected mitochondrial mutation in a pedigree with familial NA-AION. Methods Study comprised three families where more than one member developed NA-AION. All patients with NA-AION had a detailed ophthalmic, medical and family history, and comprehensive ophthalmic evaluation at initial visit and on follow-up. One patient from family 1, one from family 2, 41 non-familial NA-AION patients, 97 control subjects and 1,488 patients with suspected Leber hereditary optic neuropathy (LHON) were tested for the presence of mitochondrial mutation (G4132A) in a previously reported genetic study of family 3. Results Familial NA-AION was found in seven individuals of family 1, four of family 2 and six of family 3. Symptoms, signs and clinical findings of familial NA-AION were similar to classical NA-AION, with two exceptions: familial NA-AION had an earlier onset (47.3+8.6 years versus 60.1+13.6 years) and a higher frequency of bilateral disease. The G4132A mitochondrial variant was not detected outside family 3. None of the three major mutations associated with LHON (G3460A, G11778A, T14484C) was found among Familial NA-AION patients. Conclusions The only difference in clinical features between familial NA-AION and classical NA-AION is that the former has an earlier onset and a higher frequency of bilateral disease. The G4132A mutation is not commonly associated with familial NA-AION, and was not detected in patients with non-familial NA-AION. The role of hereditary factors in familial NA-AION remains largely unknown.