Leber Hereditary Optic Neuropathy

National Organization for Rare Disorders, Inc.

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  • Leber's optic atrophy
  • Leber's optic neuropathy
  • LHON

Disorder Subdivisions

  • None

General Discussion

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.

Affected Populations

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.

Standard Therapies


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.

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.


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.

Genetic counseling may be of assistance to patients and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


For information about clinical trials conducted in Europe, contact:


Contact for additional information about Leber hereditary optic neuropathy:

Alfredo A. Sadun, MD, PhD

Flora Thornton Professor of Vision Research

Vice-Chair Ophthalmology

Chief of Service, Neuro-Ophthalmology

Professor of Neuro-surgery

Keck-USC School of Medicine

1450 San Pablo St., Suite 5802

Los Angeles, CA 90033

323.442.6417 Office

323.442.6407 Fax



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. (Updated April 19, 2012). Leber Hereditary Optic Neuropathy. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at http://www.genetests.org. Accessed December 18, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Leber Optic Atrophy. Entry No: 535000. Last Edited August 26, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed December 18, 2012.


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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.