THE CLINICAL-FEATURES OF LEBERS HEREDITARY OPTIC NEUROPATHY DEFINED BY THE PRESENCE OF A PATHOGENIC MITOCHONDRIAL-DNA MUTATION

One hundred and seven patients from 79 families were defined as having Leber's hereditary optic neuropathy (LHON) by the presence of one of the mitochondrial DNA (mtDNA) mutations at positions 11778 (60 familie s), 3460 (seven families) or 14484 (12 families). Only half of the 117 78 index patients had a history of similarly affected relatives; this proportion was higher with the 3460 (71%) and 14484 (100%) mutations. The ratios of affected male to female patients were 2.5:1 (11778), 2:1 (3460), and 5.7:1 (14484). Detailed clinical data were available for 79 patients-from 55 families. Visual loss developed between the ages o f 11 and 30 years in 69%, with a range of 6-62 years, and no significa nt differences between mutation groups or males and females, It was bi lateral in all but two patients, to a median of counting fingers with a central scotoma, developing simultaneously in 22% and sequentially i n 78%, with a median inter-eye delay of 8 weeks, and progressing in ea ch eye over a period of 4-6 weeks. Nineteen patients had pain in an af fected eye or on eye movements, and four experienced Uhthoff's phenome non. Retinal microangiopathy was uncommon after 6 months from onset an d was not detected in 36% of patients examined within 3 months of visu al loss, the microangiopathy was particularly uncommon in the 14484 gr oup. There was no difference in the overall visual outcome between the 11778 and 3460 groups with median final visual acuities of 1/60 and 3 /60, respectively. particularly severe visual loss occurred in one-thi rd of women with the 11778 mutation, to vague perception of light or n o perception of light in at feast one eye. A multiple sclerosis-like i llness was observed in 45% of females with the 11778 mutation. Prognos is was substantially better in the 14484 patients, with recovery to a final visual acuity of at least 6/24, in 71% of patients. Good visual outcome was strongly correlated with age at onset, all those with onse t before 20 years having a final visual acuity better than 6/24 as opp osed to only 2 out of 6 with later onset. Improvement in vision occurr ed as long as 4 years after onset. High alcohol and tobacco consumptio n, cranial or ocular trauma, young or old age at presentation, co-exis ting neurological disease, and recent childbirth with post-partum haem orrhage, all contributed to diagnostic difficulties in this series, us ually in the absence of a family history. These problems were resolved by mtDNA analysis.