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.

The prevalence of LHON 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, 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.

Genetic Testing Information

• Genetic Testing Registry: Leber optic atrophy

Genetic and Rare Diseases Information Center

• Leber hereditary optic neuropathy

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• LEBER OPTIC ATROPHY
• LEBER HEREDITARY OPTIC NEUROPATHY, MODIFIER OF; LOAM

Scientific Articles on PubMed

• PubMed

• Mroczek-Tonska 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. Citation on PubMed
• Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005 Sep;140(3):517-23. doi: 10.1016/j.ajo.2005.03.017. Citation on PubMed
• 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. doi: 10.1016/j.ajo.2005.11.007. Citation on PubMed
• Tonska K, Kodron 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. Citation on PubMed
• Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy. 2000 Oct 26 [updated 2021 Mar 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1174/ Citation on PubMed
• 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. Erratum In: J Med Genet. 2011 Apr;48(4):284. Citation on PubMed or Free article on PubMed Central
• Yu-Wai-Man P, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy. J Med Genet. 2002 Mar;39(3):162-9. doi: 10.1136/jmg.39.3.162. Citation on PubMed or Free article on PubMed Central