In this section:

What is LHON?
Symptoms
Prevalence of LHON
Role of genetics and inheritance
Potential risk factors and triggers

What is LHON?

Leber’s hereditary optic neuropathy or LHON is a rare inherited condition that results in rapid central vision loss.Footnote1,Footnote2 Named after Theodore Leber, who first defined it in 1871, LHON affects approximately 1 in 45,000 people in Europe.Footnote2,Footnote3

Symptoms in LHON usually begin with painless blurring and loss of central vision in one eye and then both eyes.Footnote3,Footnote4 It results from cell dysfunction in the optic nerve and affects how patients can see things.Footnote3 Each eye gets worse as the blurry blind spot rapidly expands over 6–12 months.Footnote3,Footnote4 The duration in which the eyesight gets worse varies from a few months to more than two years.Footnote3,Footnote4

How LHON impacts vision

Normal vision
Normal vision example
LHON vision
LHON vision example

These images are for illustrative purposes only. A patient's vision may differ from that represented in the image on the right.

Symptoms

LHON begins with the following symptoms:Footnote3–Footnote5

  • Sudden central vision loss usually in one eye followed by the second eye within 8 weeks (75% of the cases); or in both eyes simultaneously (25% of the cases)Footnote5
  • Painless blurring in the centre of the eyeFootnote3,Footnote4
  • Blurring of visionFootnote4
  • Loss of sharpnessFootnote5
  • Loss of colour visionFootnote4

Individuals with LHON develop visual blurring affecting the central vision, however in some cases the peripheral vision is preserved.Footnote1,Footnote4

LHON affects the central vision needed for routine tasks such as reading, driving and recognising people. If you have LHON, you might become legally blind.Footnote5

Central vision loss is typically the only symptom of LHON

Prevalence

Men are four to five times more likely to be affected by LHON than women.Footnote4 The first signs of vision loss usually appear between the ages of 15 and 35 years.Footnote5,Footnote6 In rare cases, however, symptoms can occur between 2 and 87 years of age.Footnote1 However, the age of onset tends to be higher in women;Footnote5 LHON shows a marked bias of vision loss in menopausal women.Footnote7

Even if LHON runs in your family, one can’t predict the age at which it could be triggered, who would be affected (men or women), or the severity of the vision loss.Footnote4,Footnote5 Additional genetic and environmental factors interact with the mitochondrial DNA (mtDNA) pathogenic variant and influence whether an individual ultimately loses their sight.Footnote4

Knowing the symptoms of LHON can speed up the diagnosis journey

In men

Men are four to five times more likely to be affected by LHON than women.Footnote4

In women

The age of onset tends to be higher in women.Footnote5

Role of genetics and inheritance

LHON is a rare condition mostly caused by mutations in the mitochondrial DNA.Footnote3,Footnote6 A mother with a mitochondrial mutation passes it on to all her children.Footnote6 However, a father who has LHON cannot pass it on to any of his children.Footnote4,6 This is because the mitochondria for the developing baby predominantly come from the mother’s egg cells and rather than the father’s sperm cells.Footnote6 So, any mutations in the mitochondria can only be inherited maternally.Footnote6

Mothers with an LHON mutation will pass it on to their children

Mothers with an LHON mutation will pass it on to their children

Mothers with an LHON mutation will pass it on to their children
The mitochondria produce most of the energy that cells need to function.Footnote6 In LHON, these inherited mutations disrupt the mitochondria and cause cells in the eye to stop working or eventually, die.Footnote4,6

Mutations in one of the three major genes in mitochondria are responsible for LHON in approximately 90% of patients.Footnote4 Other rare mtDNA mutations account for a further approximately 10% of the LHON cases.Footnote4 Around one in three cases also appears to be sporadic with no definitive family history.Footnote5 In the absence of maternally-inherited LHON, mutations in a nuclear encoded gene, DNAJC30, have also been established leading to an autosomal recessive mode of inheritance for LHON (arLHON).Footnote8

However, this does not mean that all carriers of one of these genetic mutations will necessarily develop LHON.Footnote4,Footnote9 50% of male carriers and only 10% of female carriers will develop vision loss symptoms.Footnote9

Some mothers with an LHON gene mutation do not show symptoms.Footnote6 Tracing back family history often reveals female relatives with visual loss at an early age.Footnote6

Mothers with an LHON mutation will pass it on to their children.

  • The genetic mutation in the mitochondria disrupts the normal functioning of the cells in the optic nerve called the retinal ganglion cells.Footnote10 Human eyes have over a million retinal ganglion cells.Footnote10 These cells process the visual information entering our eyes. They enable us to see things by sending the image to our brain.Footnote11

    Although all the cells in the body have the same mitochondrial mutations, LHON damages the cells in the eye.Footnote4,Footnote9 The number of mitochondria in a cell depends on the energy demands of that particular cell, and retinal ganglion cells need a lot of energy.8 Mutations in LHON make the retinal ganglion cells susceptible to mitochondrial diseases.Footnote9 LHON leads to progressive loss of the retinal ganglion cells resulting in significant visual loss.Footnote10

  • Understanding the role of mitochondria in LHON

    Adapted from Cooper GM. 2000.13

    Mitochondria are organelles that exist within our cells.Footnote10 They have their own set of DNA known as mitochondrial DNA (mtDNA).Footnote10,Footnote12 They are powerhouses that help convert the energy from food into energy the cell can use.Footnote10,Footnote12

    LHON mutations
    Many mutations have been identified in people with LHON. However, approximately 90% of patients affected by LHON have one of the three common mtDNA mutations (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4, and m.14484T>C in MT-ND6).Footnote4 In the absence of maternally inherited LHON, mutations in a nuclear encoded gene DNAJC30 have also been established.Footnote8
    The mutations responsible for LHON affect the generation of energy in the mitochondria.Footnote4

Potential risk factors
and triggers

Risk factors for carriers of LHONFootnote1,Footnote4

  • Age and sex are important risk factors for LHONFootnote4
  • Young men have a lifetime risk of around 50% of developing LHON, but this percentage falls as years go by without manifestationFootnote4
  • The threat of acquiring LHON never vanishes, as it can present late in lifeFootnote1

Triggers

While women are less likely to be affected, sometimes, menopause or stopping hormone replacement therapies is also known to trigger LHON.Footnote7

Environmental factors could also contribute to vision loss and additional medical problems associated with LHON. Therefore, if you are an LHON carrier, you will be advised of the following:Footnote4

  • Do not smoke

  • Drink alcohol
    moderately

  • Avoid binge-drinking episodes

Some medications are known to damage the mitochondria. Due to this, it might be worth finding out more about these medications and discussing their use with your treating physician.Footnote4

Avoiding potential risks and triggers could be beneficial

  • Autosomal recessive inheritance: This is one of the ways a genetic trait or condition can be passed down from parent to child. In autosomal recessive inheritance, the affected individual inherits one copy of a mutated gene from each parent for a genetic condition to occur.8,14

    DNA: This is the hereditary material located inside the cells in our body and contains the information needed for that cell, and our body, to develop and function. This information is passed from parents to their children through DNA.14

    Genes: These are small sections of DNA that contain the basic physical and functional units of heredity. Most genes contain information which contributes to a specific function or characteristic.14

    Genetic: Genetics is the study of genes and heredity and how certain qualities or conditions are passed from parents to offspring as a result of changes in DNA sequence.14

    Maternal inheritance: When a mutation is passed from mothers, but not from fathers, to their children.4,14

    Mitochondria: Small structures (organelles) that exist inside our cells and generate the energy needed for that cell to function.9,14

    Mitochondrial DNA (mtDNA): DNA that is found in the mitochondria.14

    Mutations: The genes in our body act as instructions to make molecules called proteins. Changes in a gene are called mutations. These prevent one or more of the proteins to do their jobs causing disease.14

    Nuclear-encoded gene: A gene that is found in the cell nucleus.8,14

    Nucleus: The structure inside our cells which contains most of our DNA.14

    Optic nerve: The nerve that carries visual information from the retina to the brain.15

    Organelles: Organelles are special structures within a cell that perform various jobs that are crucial to a cell.10

    Pathogenic variant: This refers to a mutated gene that increases an individual’s chance of developing a specific disease or disorder.4,14

    Retinal ganglion cells: These are cells that connect the inner retina of the eye to the brain. Together, these cells form the optic nerve.10,11

    1. Theodorou-Kanakari A, et al. Adv Ther. 2018;35:1510–18.

    2. Carelli V, et al. J Neuro-Ophthalmol. 2017;37:371–81.

    3. Carelli V, et al. Eur Ophthalmic Rev. 2019;13(Suppl 2).

    4. Yu-Wai-Man P and Chinnery PF. Leber Hereditary Optic Neuropathy. GeneReviews® [Internet]. 2021. Available at: https://www.ncbi.nlm.nih.gov/books/ NBK1174/. Accessed: March 2023.

    5. Karaarslan C. Adv Ther. 2019:36;3299–307.

    6. Fraser JA, et al. Surv Ophthalmol. 2010;55:299–334.

    7. Asanad S, et al. J Curr Ophthalmol. 2019:31;251–53.

    8. Stenton SL, et al. J Clin Invest. 2021:15;131(6):e138267.

    9. Meyersen C, et al. Clin Ophthal. 2015;9:1165–76.

    10. Yu-Wai-Man P and Newman NJ. Hum Mol Genet. 2017:26;12–20.

    11. Wienbar S and Schwartz GW. Prog Retin Eye Res. 2018:67;102–17.

    12. Newmeyer DD and Ferguson-Miller S. Cell. 2003;112;481–90.

    13. Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Available at: https:// www.ncbi.nlm.nih.gov/books/NBK9896/. Accessed: March 2023.

    14. Genetic Alliance. The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2009. Available at: https://www.ncbi.nlm.nih.gov/books/NBK115558/. Accessed: March 2023.

    15. Carelli V, et al. Biochim Biophys Acta. 2009;1787(5):518–28.

    16. Cleveland Clinic–Leber Hereditary Optic Neuropathy (Sudden Vision Loss). Available at: https://my.clevelandclinic.org/health/diseases/15620-leber-hereditary-optic-neuropathy-sudden-vision-loss. Accessed: October 2023.

Disclaimer: The information on this website is intended only to provide knowledge of Leber’s hereditary optic neuropathy (LHON). This information should not be used in place of advice from a healthcare professional. Please contact your doctor for advice. This website has been produced by Chiesi Pharmaceuticals. The website has been developed in accordance with industry and legal standards to provide information for the general public about LHON. Chiesi Pharmaceuticals makes every reasonable effort to include accurate and current information. However, the information provided in this website is not exhaustive.