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Disease Profile

Leber hereditary optic neuropathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adolescent

ICD-10

H47.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Leber’s disease; Optic atrophy, Leber type; Leber optic atrophy;

Categories

Congenital and Genetic Diseases; Eye diseases; Heart Diseases;

Summary

Leber hereditary optic neuropathy (LHON) is a condition characterized by vision loss. Vision loss is typically the only symptom of LHON. Some families with additional signs and symptoms have been reported and are said to have "LHON plus", a condition which includes vision loss, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Some affected individuals develop features similar to multiple sclerosis. LHON is caused by mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes. LHON has a mitochondrial pattern of inheritance; however, there are many cases in which there are no other cases of LHON in the family.[1] Treatment is supportive and may include visual aids. There is ongoing research for more effective treatment.[2]

Symptoms

Leber hereditary optic neuropathy (LHON) is characterized by bilateral, painless, and almost sudden vision failure that develops in young adulthood (around 20 to 30 years of age). About 95% of affected people lose their vision before age 50. It is more common in males. Signs and symptoms include:[1][3]

  • Blurring and clouding of vision (usually the first symptoms) affecting the central visual field
  • Severe loss of visual acuity (sharpness of vision) and color vision over time
  • Loss of ability to complete visual tasks such as reading, driving, and recognizing faces
  • A growing, dense central scotoma (blind spot) seen during visual field testing
  • Development of optic atrophy

Most people with LHON eventually qualify for registration as legally blind.[3]

In rare cases, additional symptoms may include heart arrhythmias; neurologic abnormalities (e.g., tremor, peripheral neuropathy, movement disorders); and features similar to those seen in multiple sclerosis.[1][3]

A significant proportion of people with a mutation known to cause LHON do not develop any features. Specifically, more than 50% of males with a mutation and more than 85% of females with a mutation never experience vision loss or related medical problems.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Mitochondrial respiratory chain defects
0200125
Slow decrease in visual acuity
Slow decrease in sharpness of vision
0007924
30%-79% of people have these symptoms
Blurred vision
0000622
Central scotoma
Central blind spot
0000603
Centrocecal scotoma
0000576
Optic atrophy
0000648
Optic neuropathy
Damaged optic nerve
0001138
Retinal telangiectasia
0007763
Retinal vascular tortuosity
0012841
5%-29% of people have these symptoms
Ataxia
0001251
Myopathy
Muscle tissue disease
0003198
Peripheral neuropathy
0009830
Postural tremor
0002174
Ventricular preexcitation
0004309
Percent of people who have these symptoms is not available through HPO
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Central retinal vessel vascular tortuosity
0007768
Dystonia
0001332
Incomplete penetrance
0003829
Leber optic atrophy
0001112
Mitochondrial inheritance
0001427
Polyneuropathy
Peripheral nerve disease
0001271
Visual loss
Loss of vision
Vision loss

[ more ]

0000572

Cause

Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause LHON. These genes are contained in mitochondrial DNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA).[1]

The genes related to Leber hereditary optic neuropathy each provide instructions for making a protein involved in normal mitochondrial function. These proteins are part of a large enzyme complex in mitochondria that helps convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy.[1] Please visit the Genetic Home Reference Web site to learn more about how mutations in these genes cause Leber hereditary optic neuropathy.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Currently, there is no cure for this disease but there are several ongoing studies aiming to find an effective treatment. Management of affected individuals is usually supportive, with provision of visual aids.[2]

    High-dose oral idebenone may be considered as a treatment option, especially for individuals with LHON with relatively recent disease onset. Some studies have reported a benefit from using idebenone with quinone analogues, such as ubiquinone (Coenzyme Q10) and with vitamin C and vitamin B12.[2]

    In an open-label study of five individuals with acute LHON treated within 90 days of disease onset, the antioxidant α-tocotrienol-quinone (EPI-743), a vitamin E derivative, showed good results.[2]

    Those with established LHON mitochondrial DNA mutations are advised not to smoke and to limit their alcohol intake. People with Leber hereditary optic neuropathy may also find it helpful to speak with other affected individuals and to seek extra psychosocial or counseling support.[2]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Leber hereditary optic neuropathy. Click on the link to view a sample search on this topic.

            References

            1. Leber hereditary optic neuropathy. Genetics Home Reference (GHR). 2013; https://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy.
            2. Yu-Wai-Man P & Chinnery PF. Leber Hereditary Optic Neuropathy. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK1174/.
            3. Patrick Yu-Wai-Man, Patrick F Chinnery. Leber Hereditary Optic Neuropathy. GeneReviews. June 23, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1174/.

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