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Leber Hereditary Optic Neuropathy

Last updated Oct. 26, 2018

Approved by: Maulik P. Purohit MD, MPH

Leber Hereditary Optic Neuropathy (LHON) is a genetic disorder that leads to loss of sight. The onset of LHON can occur at any age, although typically, the symptoms begin in the teens and twenties.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Hereditary Optic Neuroretinopathy
  • Leber's Optic Atrophy
  • LHON (Leber Hereditary Optic Neuropathy)

What is Leber Hereditary Optic Neuropathy? (Definition/Background Information)

  • Leber Hereditary Optic Neuropathy (LHON) is a genetic disorder that leads to loss of sight. The onset of LHON can occur at any age, although typically, the symptoms begin in the teens and twenties
  • Leber Hereditary Optic Neuropathy is a hereditary disorder, and therefore, inheriting a mutation in one of the many causative genes is the greatest risk factor for being diagnosed with the condition. If one already has the condition, certain toxins, environmental pollutants, and medications are known to exacerbate it
  • Leber Hereditary Optic Neuropathy is caused by mutations in MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes. The MT in the gene nomenclature indicates “mitochondrial.” These genes are localized in the mitochondrial DNA of an individual
    • Mitochondria are cellular organelles that are the “powerhouses” of cells and sites of cellular respiration and energy synthesis
    • They carry their own DNA, which an individual inherits from the mother
  • These genes code for proteins that are involved in the mitochondrial function of energy generation. The exact mechanism of genetic mutations leading to Leber Hereditary Optic Neuropathy is still under scientific investigation
  • The pattern of inheritance of Leber Hereditary Optic Neuropathy is mitochondrial, and the inheritance occurs exclusively from the mother. During the fertilization process, the father’s nucleus enters the egg, and the latter provides the mitochondria for the developing embryo
  • The symptoms of LHON begin with blurring and clouding of vision, leading to loss of sharp focus, and then to loss of vision. Some affected individuals with “LHON Plus” exhibit additional symptoms that include tremors, impaired movement owing to muscle weakness and lack of coordination, and abnormalities of electrical conductivity in the heart
  • Some potential complications of the disorder are permanent loss of vision; those with “LHON Plus” may develop stroke, cardiac arrhythmia, and movement disorders
  • Early Leber Hereditary Optic Neuropathy is treated with vitamin E supplements and visual aids. Cessation of smoking and limiting exposure to environmental toxins can help limit damage to vision. This may also require a reassessment of one’s living and working conditions
  • Leber Hereditary Optic Neuropathy is an inherited disorder and there are no guidelines or methods to prevent its occurrence. If there is a positive family history of the condition, genetic testing of fetal cells and genetic counseling can help prospective parents understand the condition better. Smoking cessation and minimizing exposure to environmental toxins may help avoid aggravating the condition in the affected individuals
  • Leber Hereditary Optic Neuropathy is manageable with timely diagnosis and prompt, continual treatment. A delay or lack of treatment can lead to permanent loss of vision, as well as heart and brain related conditions (which are observed in some cases)

Who gets Leber Hereditary Optic Neuropathy? (Age and Sex Distribution)

  • Leber Hereditary Optic Neuropathy is an eye disorder whose worldwide prevalence is not known. In Finland, the Netherlands and England, the incidence rate of this disorder is reported to be higher at 1:30,000 to 1:50,000
  • Even though it is a congenital disorder, the age of onset is in the teens and twenties. However, rarely, it can present itself in childhood or much later, into late adulthood as well
  • The condition can occur in both genders. However, males are 4-5 times more susceptible to LHON in comparison to females

What are the Risk Factors for Leber Hereditary Optic Neuropathy? (Predisposing Factors)

  • Leber Hereditary Optic Neuropathy is caused by genetic factors and therefore, having mutations in certain mitochondrial genes is a risk factor for developing the condition
  • However, it must be noted that not all individuals with the mutation(s) develop LHON. About 50% of the males and 85% of females with mutations in the causative genes do not develop the disorder
  • It is believed that some environmental toxins may be contributing to the disorder, since it can develop in individuals with no family history of LHON

Factors/materials that can aggravate Leber Hereditary Optic Neuropathy include toxic chemicals, drugs, and other products including:

  • Tobacco
  • Alcohol
  • Medications used to treat cancer, AIDS, malaria, blood pressure, heart conditions, and seizures including certain antibiotics
  • Fumes and vapors of hair products, paints, varnishes, etc.
  • Stress hormones released by the body
  • Cyanogens (pungent toxic gases found in very slight quantities in legumes and nuts)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Leber Hereditary Optic Neuropathy? (Etiology)

  • Leber Hereditary Optic Neuropathy is a genetic disorder. It is caused by mutations in the MT-ND1, MT-ND4, MT-ND4L and MT-ND6 genes. These genes are located in the mitochondria and not the nucleus of cells
    • Mitochondria are double-membrane cellular organelles present in numerous quantities inside cells
    • These organelles are the sites of cellular respiration and energy generation, and are known as the “powerhouses” of cells
    • Mitochondria carry their own DNA. Since the egg contributes the cellular environment for fertilization and subsequent embryonic development, the mitochondria are inherited exclusively from the mother (to the offspring)
  • Leber Hereditary Optic Neuropathy is inherited in a mitochondrial or maternal inheritance pattern. In this type of inheritance, only mothers pass the gene mutations to their offspring
  • Under normal circumstances, these genes code for proteins that are components of an enzyme complex that catalyzes the conversion of simple sugars to adenosine triphosphates (or ATPs) in the presence of oxygen. The cellular energy is stored in the form of ATP molecules
  • Mutations in the said genes cause malfunction of the energy generating apparatus. However, the exact mechanism by which this ‘compromised energy generation’ causes cells to die in the optic nerve, and consequently result in Leber Hereditary Optic Neuropathy is unclear. This is currently under scientific investigation
  • Since males are observed to be significantly more susceptible to LHON than females, research is also being conducted to check for the involvement of genes on the X chromosome. Males inherit only one X chromosome from the mother

What are the Signs and Symptoms of Leber Hereditary Optic Neuropathy?

The following signs and symptoms may be observed in individuals with Leber Hereditary Optic Neuropathy:

  • Blurring vision, in one or both eyes
  • Clouding of vision, in one or both eyes
  • Reduced visual acuity
  • Loss of color vision

In some affected individuals, in whom the condition is classified as “LHON Plus”, one or many of the following symptoms may be present in addition to the above-mentioned vision abnormalities:

  • Muscle weakness
  • Uncoordinated movements
  • Numbness
  • Tremors
  • Erratic heartbeats
  • Symptoms similar to multiple sclerosis: This is observed predominantly in women with LHON Plus type of disorder

How is Leber Hereditary Optic Neuropathy Diagnosed?

The diagnosis of Leber Hereditary Optic Neuropathy is based on ophthalmologic findings. Information from the following tests and procedures may be needed for an accurate diagnosis of the condition:

  • A thorough physical examination with an assessment of symptoms
  • An evaluation of one’s family medical history
  • Blood tests
  • Eye exam
  • Neuroimaging studies
  • Prenatal diagnosis through ultrasound scans
  • Genetic testing and analysis to identify the causative gene
  • Differential diagnosis to distinguish between LHON and other conditions that can result in similar symptoms

Note: The genetic testing should include all blood-related family members of the affected individual. This can help prevent the disorder affecting other individuals or family members at a later stage.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Leber Hereditary Optic Neuropathy?

Complications due to Leber Hereditary Optic Neuropathy may include:

  • Permanent loss of vision
  • LHON Plus, wherein in addition to vision defect, the brain gets affected leading to loss of control of muscle movements causing cardiac arrhythmia, tremor, and multiple sclerosis like symptoms
  • Stroke due to an increase in blood pressure; hypertensive crisis

How is Leber Hereditary Optic Neuropathy Treated?

An early diagnosis and appropriate treatment is very crucial to reducing the damaging effect of Leber Hereditary Optic Neuropathy, since it is an incurable disorder. The treatment measures include:

  • Minimizing or completely stopping the consumption of tobacco and alcohol: An occupational rehabilitation and lifestyle modification may be considered after assessing the current living and work environment condition, drugs in use, and other factors
  • Use of visual aids to help improve vision and one’s quality of life
  • An intake of vitamin E has shown to improve vision, if the disorder is in its early stages

Clinical trials are presently underway for various medications and techniques that might aid in LHON management.

How can Leber Hereditary Optic Neuropathy be Prevented?

Currently, there are no specific methods or guidelines to prevent Leber Hereditary Optic Neuropathy, since it is a genetic condition.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as LHON
  • Avoiding toxic chemicals and medications may help avoid aggravating the condition
  • Regular medical screening at periodic intervals with tests, scans, and physical examinations are advised

What is the Prognosis of Leber Hereditary Optic Neuropathy? (Outcomes/Resolutions)

  • With timely, active treatment administration, Leber Hereditary Optic Neuropathy can be effectively managed and controlled
  • Such measures have to include changes in an individual’s work nature and living conditions (as appropriate). A lifelong management of LHON is required
  • Non-treatment or delayed treatment of the disorder can lead to complete vision loss (in both eyes) and other heart and brain related complications

Additional and Relevant Useful Information for Leber Hereditary Optic Neuropathy:

Some of the researches being conducted to manage LHON include the use of antioxidants, stem cell therapy, hyperbaric oxygen therapy, use of infrared light, virus vector gene therapy, etc.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Jan. 4, 2017
Last updated: Oct. 26, 2018