Identical Twins No Longer Discordant for Leber's Hereditary Optic Neuropathy | Genetics and Genomics | JAMA Ophthalmology | JAMA Network
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Case Reports and Small Case Series
July 1998

Identical Twins No Longer Discordant for Leber's Hereditary Optic Neuropathy

Arch Ophthalmol. 1998;116(7):956-957. doi:

In 1993, Johns and colleagues1 described 2 monozygous twin brothers who had remained discordant for the development of Leber's hereditary optic neuropathy (LHON) for 6.5 years. Both brothers were found to harbor the identical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations. Twin A developed bilateral optic neuropathy at the age of 34 years and had a visual acuity of 1/200 OU. At the time of the report, twin B was 41 years old and still had a visual acuity of 20/15 OU with no signs or symptoms of LHON. In this current report, updated information on twin B is provided and indicates that twin B has subsequently developed bilateral LHON.

Report of a Case

Twin B, now 45 years old, had remained healthy and visually asymptomatic until he noted painless, blurred vision while driving on the morning of September 23, 1997. The visual loss first occurred in the left eye and then in the right eye 1 hour later. The patient reported no trauma, recent illness, weight change, or any unusual environmental exposure. He has continued to smoke 1 pack of cigarettes daily and to drink 24 beers weekly for the past 25 years. He was a firefighter but had not worked in this capacity for 2 years. He has been a part-time painter and has used latex paint for many years. His only medication was Ex-Lax twice a month for constipation since age 38. He has experienced much stress in the past year due to an ongoing litigation against his former employer for a nonphysically related matter. His daily activity has remained unchanged except for starting an exercise regimen 1 month prior to the visual loss. His typical routine was a 1-mile light run, 45 sit-ups, and 30 push-ups twice a week.

On examination, best visual acuity was count fingers at 4 inches OU. Pupillary reaction in both eyes was sluggish to light with no relative afferent pupillary defect. Goldmann perimetry demonstrated large central scotomas in both eyes. Intraocular pressures were 17 mm Hg OU. The optic nerves were hyperemic with a cup-disc ratio of 0.5 and no peripapillary vascular telangiectasia. The maculae and retinal vasculature appeared normal.


Updated information indicates that the discordance for LHON reported previously for a pair of monozygous twin brothers1 is temporal and not absolute. The discordance of the onset of LHON is 11 years, and the phenotypic findings are similar.

Potential mitigating factors such as excessive tobacco and alcohol use have been suggested in the phenotypic expression of LHON.2-4 In this case, both twins smoked 1 pack of cigarettes daily. However, twin A drank 6 to 12 beers weekly, which is less than half of the amount consumed by twin B who in fact had a much later onset of LHON. Both twins were firefighters, and twin A experienced visual loss 2 weeks after exposure to smoke. In contrast, twin B had not worked as a firefighter for 2 years and reported no recent exposure to smoke. The only recent change in his routine was starting a light exercise regimen 1 month prior to the visual loss. He did, however, report experiencing much stress for more than a year due to ongoing litigation. Interestingly, both twins noted the onset of visual loss while driving. However, this is a common activity and has not been associated with the onset of LHON.

In short, no common identifiable epigenetic factor for the clinical expression of LHON is apparent for these 2 monozygous twins who had a discordance for the onset of LHON of 11 years. This suggests that potential epigenetic factors for the clinical expression of LHON are variable and may be numerous.

Corresponding author: Byron L. Lam, MD, 900 NW 17th St, Miami, FL 33136.

Johns  DRSmith  KHMiller  NRSulewski  MEBias  WB Identical twins who are discordant for Leber's hereditary optic neuropathy.  Arch Ophthalmol. 1993;1111491- 1494Google ScholarCrossref
Newman  NJLott  MTWallace  DC The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation.  Am J Ophthalmol. 1991;111750- 762Google Scholar
Johns  DRSmith  KHSavino  PJMiller  NR Leber's hereditary optic neuropathy: clinical manifestations of the 15257 mutation.  Ophthalmology. 1993;100981- 986Google ScholarCrossref
Johns  DRHeber  KLMiller  NRSmith  KH Leber's hereditary optic neuropathy: clinical manifestations of the 14484 mutation.  Arch Ophthalmol. 1993;111495- 498Google ScholarCrossref