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Leber hereditary optic neuropathy (LHON) is an inherited form of vision loss. Although this condition usually begins in a person's teens or twenties, rare cases may appear in early childhood or later in adulthood. For unknown reasons, males are affected much more often than females.
Blurring and clouding of vision are usually the first symptoms of this disorder. These vision problems may begin in one eye or simultaneously in both eyes; if vision loss starts in one eye, the other eye is usually affected within several weeks or months. Over time, vision in both eyes worsens with a severe loss of sharpness (visual acuity) and color vision. This condition mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Vision loss results from the death of cells in the nerve that relays visual information from the eyes to the brain (the optic nerve). Although central vision gradually improves in a small percentage of cases, in most cases the vision loss is profound and permanent.
Painless vision loss is typically the only symptom of Leber hereditary optic neuropathy; however, some families with other signs and symptoms have been reported. These cases are described as "LHON plus." In addition to vision loss, the features of LHON plus can include movement disorders, tremors, and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects). Additionally, some people with Leber hereditary optic neuropathy develop features similar to multiple sclerosis. Multiple sclerosis is a chronic disorder that affects the brain and spinal cord (the central nervous system), causing muscle weakness, poor coordination, numbness, and a variety of other medical problems.
The prevalence of Leber hereditary optic neuropathy in most populations is unknown. It affects 1 in 30,000 to 50,000 people in northeast England and Finland.
Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause Leber hereditary optic neuropathy. 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).
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.
A significant percentage of people with a mutation that causes Leber hereditary optic neuropathy do not develop any features of the disorder. Specifically, 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 of these factors have produced conflicting results. Researchers are also investigating whether changes in additional genes, particularly genes on the X chromosome, contribute to the development of signs and symptoms.
Changes involving this chromosome are associated with Leber hereditary optic neuropathy.
Changes in these genes are associated with Leber hereditary optic neuropathy.
This condition has a mitochondrial pattern of inheritance, which is also known as maternal inheritance. This inheritance pattern applies to genes contained in mitochondrial DNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.
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.
These resources address the diagnosis or management of Leber hereditary optic neuropathy and may include treatment providers.
You might also find information on the diagnosis or management of Leber hereditary optic neuropathy in Educational resources (http://www.ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy/show/Patient+support).
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
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You may find the following resources about Leber hereditary optic neuropathy helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
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