The following information may help to address your question:
What is Leber hereditary optic neuropathy (LHON)?
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]
Last updated: 3/13/2017
What causes Leber hereditary optic neuropathy (LHON)?
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.
Last updated: 3/13/2017
Do all people with these gene mutations develop Leber hereditary optic neuropathy (LHON)?
No. Many people with a mutation that causes LHON do not develop any features of the disorder (more than 50% of males with a mutation and more than 85 % of females with a mutation never will have vision loss or other medical problems related to LHON). Additional factors, including the specific gene mutation that the person has, may determine whether a person develops the signs and symptoms of this disorder.
Environmental factors such as smoking and alcohol use may also be involved, although studies of these factors are conflicting.
[1]
Last updated: 6/17/2016
What are the signs and symptoms of Leber hereditary optic neuropathy (LHON)?
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]
Last updated: 3/13/2017
Is the vision loss due to Leber hereditary optic neuropathy (LHON) permanent?
Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent. The vision loss often begins in young adults. However, the rate of vision loss varies considerably, from sudden severe vision loss within one day, to gradual vision loss over the course of months. Also, once the vision stabilizes, further vision changes appear to be rare.
[2]
Last updated: 6/17/2016
Will the vision loss associated with Leber hereditary optic neuropathy (LHON) improve with time?
Partial recovery of vision loss has been reported, but this is rare. When partial recovery does occur it tends to begin around 6 months to several years after disease onset. The chance of vision recovery appears to be higher with certain gene mutations, namely
MT-ND6 (37% experience some recovery),
MT-ND1 (22% experience some recovery), and the
MT-CYB (28% experience some recovery).
[2] Please visit the following link from GeneReviews to learn more about visual recovery rates according to the specific mutation:
Visual Recovery Rates by Pathogenic Variant in Individuals with LHON
Last updated: 6/17/2016
Are most people with Leber hereditary optic neuropathy (LHON) blind?
The severity of the vision loss experienced by people with Leber hereditary optic neuropathy varies. Visual acuity (sharpness) can range from
20/50 to no light perception, and depends on the nature of the gene mutation. Many people with this condition lose almost all of their central vision, and have profoundly affected color vision, but may have some remaining peripheral vision.
[2] Most of these individuals can be considered legally blind. Vision tends to be most severely impaired in people with the
MT-ND4 gene mutation, followed in order of decreasing severity by those with
MT-ND1,
MT-CYB, and
MT-ND6.
[4] Also, patients who has an e
arlier age of onset (< 20 years), slow visual deterioration, and a relatively large optic disc seem to have a better prognosis.[2]
Last updated: 6/17/2016
How is Leber hereditary optic neuropathy (LHON) inherited?
Leber hereditary optic neuropathy is an
inherited condition that has a mitochondrial pattern of inheritance. The gene mutations that cause this condition are found in the
mitochondrial DNA. Mitochondria are inherited from a person's mother, and as a result, only females pass mitochondrial conditions on to their children. Men can be affected, but they cannot pass the condition on to their children.
[1]
Often, people who develop the features of Leber hereditary optic neuropathy have no
family history of the condition. Because a person may carry a mitochondrial DNA mutation without experiencing any signs or symptoms, it is hard to predict which members of a family who carry a mutation will eventually develop vision loss or other medical problems associated with Leber hereditary optic neuropathy. It is important to note that all females with a mitochondrial DNA mutation, even those who do not have any signs or symptoms, will pass the genetic change to their children.
[1]
Last updated: 3/13/2017
What are the chances that a woman with Leber hereditary optic neuropathy (LHON) will pass the mutation on to her children?
Women with LHON who have a
mitochondrial DNA gene mutation will always pass the mutation on to her children. However, more than 50 percent of males with a mutation and more than 85 percent of females with a mutation never experience vision loss or related medical problems.
Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, although studies have produced conflicting results. Researchers are also investigating whether changes in additional genes (nuclear DNA genes; Nuclear DNA is found within the nucleus of our cells), contribute to the development of signs and symptoms. As a result, is it very difficult to predict the likelihood a child will develop vision loss.
[1]
Last updated: 6/17/2016
Can certain foods or vitamins prevent vision loss in those with Leber hereditary optic neuropathy (LHON)? Can surgery be done to fix the vision loss?
There is no specific therapy or surgery to treat or prevent the specific vision loss due to Leber hereditary optic neuropathy. While vitamin supplements have been advocated, they have not been confirmed to be of value.
[4] Management of affected individuals is usually supportive, with provision of visual aids. Those with established LHON mitochondrial DNA mutations are advised not to smoke and to moderate 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]
Small studies have reported a benefit from using quinone analogues, such as ubiquinone (Coenzyme Q10) and idebenone, during the acute phase of this condition, associated with vitamin C and vitamin B12. Targeted gene therapy is under exploration.[2]High-dose oral idebenone should therefore be considered as a treatment option, especially for individuals with LHON with relatively recent disease onset. 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]
Last updated: 6/17/2016
Who can I contact to learn more about Leber hereditary optic neuropathy (LHON)?
For more information on this condition, contact The National Eye Institute (NEI), part of the National Institutes of Health (NIH).
National Eye Institute (NEI)
Information Office
31 Center Drive MSC 2510
Bethesda, MD 20892-2510
Telephone: 301-496-5248
E-mail:
2020@nei.nih.govWeb site:
http://www.nei.nih.gov/
Last updated: 12/2/2011
Are there any support groups for people with Leber hereditary optic neuropathy (LHON)?
Yes. To view a list of organizations that provide support and additional information on Leber hereditary optic neuropathy,
click here.
Last updated: 12/2/2011
We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please
contact us.
Warm regards,
GARD Information Specialist
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