Atypical Leber's hereditary optic neuropathy with molecular confirmation.

OBJECTIVE Leber's hereditary optic neuropathy (LHON) is typically a familial disease of primarily young, male adults. Analysis of mitochondrial DNA has identified point mutations associated with LHON and allowed us to identify cases of LHON not consistent with traditional descriptions of the disease. DATA SOURCES The collective experience of three tertiary referral centers contributed to this report. STUDY SELECTION Patients with bilateral optic neuropathies who were positive for the 11778 LHON mutation were included in this study if they were female and there was no family history of visual loss. DATA EXTRACTION Six case histories are presented. DATA SYNTHESIS The diagnosis of LHON remained unknown in six female patients with bilateral optic neuropathies until molecular analysis revealed the 11778 mitochondrial DNA mutation. None of the patients had a family history of visual loss, and five were initially diagnosed as having factitious visual loss. Other individual features atypical for LHON included lack of the characteristic LHON funduscopic appearance, bitemporal hemianopia, optic disc cupping, and premonitory episodes of transient visual loss. In one patient the correct diagnosis was delayed 17 years. CONCLUSIONS The diagnosis of LHON should be considered in all cases of unexplained optic neuropathy, including those with negative family history, late or early age at onset, female gender, or normal funduscopic appearance.