NORD gratefully acknowledges Joseph Kim, NORD Intern from the University of Notre Dame, and Alfredo A. Sadun, MD, PhD, F. Thornton Endowed Chair and Professor of Ophthalmology, Doheny Eye Institute / UCLA, for assistance in the preparation of this report.
Leber hereditary optic neuropathy (LHON) is mainly characterized by bilateral, painless subacute loss of central vision during young adult life. In most cases, symptoms begin with one eye first, followed a few weeks later by visual failure in the other eye. Extremely rarely there may be neurologic abnormalities, such as peripheral neuropathy, postural tremor, nonspecific myopathy, and movement disorders. LHON is caused by mutations in mitochondrial DNA and it is transmitted by maternal inheritance. LHON affects approximately 1:50,000 people. Many carriers never suffer significant visual loss; males are about four to five times more likely than females to be affected.
Individuals with LHON typically display symptoms in their young adult years. If vision is lost, then it usually occurs before 40 years of age.
The acute phase of LHON is characterized by a loss of central vision, including blurring and reduced perception of color. Individuals usually lose vision in one eye first and then lose vision in the other eye after two to three months. The atrophic phase is characterized by bilateral optic atrophy, resulting in lifelong blindness.
Depending on the mutation and pedigree, most female carriers do not lose vision but upt to half of males do.
LHON is caused by genetic mutations in the mitochondrial DNA (mtDNA). Some mothers with a LHON gene mutation do not show symptoms, but family history often reveals female relatives with visual loss at an early age.
Mutations in mitochondrial DNA can only be inherited maternally because ova contain mitochondria, while sperm do not. All of the offspring of a mother with an mtDNA mutation will inherit the gene. A male with a mitochondrial DNA mutation cannot transmit the mutated gene to any of his children.
The three primary mitochondrial DNA LHON-causing mutations are mt.3460G>A, mt.11778G>A, and mt.14484T>C, which account for over 90% of LHON patients. The most common LHON-causing mutation is mt.11778G>A. The greatest penetrance (chance of a carrier to lose vision) is for mt.3460G>A and the least is for mt.14484 T>C.
LHON affects both males and females and can only be inherited from a female. The birth prevalence of LHON is approximately 1 in 50,000 people.
LHON is diagnosed based on ophthalmologic findings, which include specialized visual testing. The testing involves dilated fundus examination to identify characteristic changes in the optic disc and vascular changes during the acute phase, electrophysiologic studies, and neuroimaging. Molecular genetic testing for mitochondrial genes associated with LHON can be used to confirm diagnosis. Most affected individuals know if their family members also are affected by LHON.
Affected individuals should receive supportive management and treatment through the usage of visual aids, occupational rehabilitation, and local social services. Small studies have shown that therapies involving ubiquinone and idebenone may provide possible benefits during the acute phase of the disorder. Affected individuals should avoid smoking and excessive alcohol consumption, which causes stress to mitochondrial energy production.
Clinical Testing and Work-Up
Consistent monitoring and surveillance of asymptomatic individuals with LHON-causing mutations is not necessary. However, if visual disturbance is experienced, affected individuals should immediately seek medical attention from an ophthalmologist or neuro-ophthalmologist .
Individuals should follow-up frequent to their own circumstances and availability of local healthcare.
Genetic counseling may be of assistance to patients and their families.
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Contact for additional information about Leber hereditary optic neuropathy:
Alfredo A. Sadun, MD, PhD
Flora Thornton Chair, Doheny Eye Institute
Vice-Chair Ophthalmology, UCLA
800 Fairmont St. suite 215
Pasadena, CA 91105
Biousse V, Newman NJ. Leber Hereditary Optic Neuropathy. In: The NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott, Williams and Wilkins; 2003:653.
Sadun AA, Carelli V, Salomao SR, Berezovsky A, Quiros PA, Sadun F, DeNegri AM, Andrade R, Moraes M, Passos A, Kjaer P, Pereira J, Valentino ML, Schein S, Belfort R. Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am J Ophthalmol. 2003 Aug;136(2):231-8.
Man PY, Griffiths PG, Brown DT, Howell N, Turnbull DM, Chinnery PF. The epidemiology of Leber hereditary optic neuropathy in the northeast of England. Am J Hum Genet. 2003;72:333-9.
Horvath R, Abicht A, Scoubridge EA, et al. Leber’s hereditary optic neuropathy presenting as multiple sclerosis-like disease of the CNS. J Neurol. 2000;247:65-7.
Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, DaCosta J, Harding AE. The clinical features of Leber’s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118(pt 2):319-37.
Mashima Y, Hilda Y, Oguchi Y. Remission of Leber’s hereditary optic neuropathy with idebenone. Lancet. 1992;340:368-9.
Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242:1427-30.
Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy. 2000 Oct 26 [Updated 2013 Sep 19]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1174/ Accessed March 9, 2016.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Leber Optic Atrophy. Entry No: 535000. Last Edited 12/20/2012. Available at: http://omim.org/entry/535000 Accessed March 9, 2016.
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