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Leber hereditary optic neuropathy

Reviewed December 2013

What is Leber hereditary optic neuropathy?

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 LHON. 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.

Vision loss is typically the only symptom of LHON; however, some families with additional signs and symptoms have been reported. In these individuals, the condition is 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). Some affected individuals develop features similar to multiple sclerosis, which is a chronic disorder characterized by muscle weakness, poor coordination, numbness, and a variety of other health problems.

How common is Leber hereditary optic neuropathy?

The prevalence of LHON in most populations is unknown. It affects 1 in 30,000 to 50,000 people in northeast England and Finland.

What are the genetic changes related to Leber hereditary optic neuropathy?

Mutations in the MT-ND1, MT-ND4, MT-ND4L, or MT-ND6 gene can cause LHON. These genes are found in the DNA of cellular structures called mitochondria, which 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 associated with LHON 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, fats, 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 LHON.

A significant percentage of people with a mutation that causes LHON 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 health 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 contribute to the development of signs and symptoms.

Related Gene(s)

Changes in these genes are associated with Leber hereditary optic neuropathy.

  • MT-ND1
  • MT-ND4
  • MT-ND4L
  • MT-ND6

How do people inherit Leber hereditary optic neuropathy?

LHON 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 LHON 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 problems associated with LHON. 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.

Where can I find information about diagnosis or management of Leber hereditary optic neuropathy?

These resources address the diagnosis or management of Leber hereditary optic neuropathy and may include treatment providers.

  • Gene Review: Leber Hereditary Optic Neuropathy (http://www.ncbi.nlm.nih.gov/books/NBK1174)
  • Gene Review: Mitochondrial Disorders Overview (http://www.ncbi.nlm.nih.gov/books/NBK1224)
  • Genetic Testing Registry: Leber's optic atrophy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0917796)
  • MedlinePlus Encyclopedia: Blindness (http://www.nlm.nih.gov/medlineplus/ency/article/003040.htm)
  • MedlinePlus Encyclopedia: Blindness - Resources (http://www.nlm.nih.gov/medlineplus/ency/article/002186.htm)

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).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Leber hereditary optic neuropathy?

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.

What other names do people use for Leber hereditary optic neuropathy?

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

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.

What if I still have specific questions about Leber hereditary optic neuropathy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Leber hereditary optic neuropathy?

atrophy ; cardiac ; chronic ; DNA ; egg ; embryo ; enzyme ; family history ; gene ; hereditary ; inheritance ; inheritance pattern ; inherited ; maternal ; maternal inheritance ; mitochondria ; mutation ; neuropathy ; nucleus ; optic atrophy ; optic nerve ; oxygen ; pattern of inheritance ; prevalence ; protein ; sclerosis ; sperm ; symptom ; visual acuity

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: Leber Hereditary Optic Neuropathy (http://www.ncbi.nlm.nih.gov/books/NBK1174)
  • Man PY, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy. J Med Genet. 2002 Mar;39(3):162-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11897814?dopt=Abstract)
  • Mroczek-Tońska K, Kisiel B, Piechota J, Bartnik E. Leber hereditary optic neuropathy--a disease with a known molecular basis but a mysterious mechanism of pathology. J Appl Genet. 2003;44(4):529-38. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14617834?dopt=Abstract)
  • Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005 Sep;140(3):517-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16083845?dopt=Abstract)
  • Spruijt L, Kolbach DN, de Coo RF, Plomp AS, Bauer NJ, Smeets HJ, de Die-Smulders CE. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy. Am J Ophthalmol. 2006 Apr;141(4):676-82. (http://www.ncbi.nlm.nih.gov/pubmed/16564802?dopt=Abstract)
  • Tońska K, Kodroń A, Bartnik E. Genotype-phenotype correlations in Leber hereditary optic neuropathy. Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1119-23. doi: 10.1016/j.bbabio.2010.02.032. Epub 2010 Mar 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20211598?dopt=Abstract)
  • Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. Inherited mitochondrial optic neuropathies. J Med Genet. 2009 Mar;46(3):145-58. doi: 10.1136/jmg.2007.054270. Epub 2008 Nov 10. Review. Erratum in: J Med Genet. 2011 Apr;48(4):284. (http://www.ncbi.nlm.nih.gov/pubmed/19001017?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2013
Published: December 22, 2014