Atypical Leber's hereditary optic neuropathy with molecular confirmation
N. C. Weiner, N. J. Newman, S. Lessell, D. R. Johns, M. T. Lott and D. C. Wallace
Department of Ophthalmology, Harvard Medical School, Boston, Mass.
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.
