Leber hereditary optic neuropathy, also known as LHON or Leber optic neuropathy, is an inherited genetic condition. It often causes loss of central vision, starting in one eye and eventually affecting both eyes.
People with the condition most commonly experience symptoms in early adulthood, and males tend to experience associated vision loss more often than females, according to 2013 research. However, many people with the LHON genetic variant never experience vision loss.
This article explains LHON, including symptoms, causes, and treatment.
A note about sex and gender
Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.
LHON passes down through families through genes. Only females, not males, can pass it on to their children.
Who is at risk?
An estimated 1 in 50,000 people with LHON develop vision loss. This means most people who carry the genetic variant that causes LHON never experience significant vision loss. That said, males have a four- to five-fold increased risk of losing sight compared to females.
If a person who carries the LHON genetic variant is going to lose their vision, it will often happen before the age of 40 years old.
The phases or stages of LHON development
- Asymptomatic phase: In this stage, there may be recognizable eye changes during exams, such as swelling.
- Subacute phase: This is 6 months from when clinical symptoms began. Vision may start to decrease, which may be when a person decides to contact a doctor.
- Dynamic phase: This is from 6 months to 1 year after symptoms begin. It ends with the chronic stage of the disease.
During the acute phase of the condition, a person loses their central vision. This typically includes blurred vision and a reduced ability to differentiate between colors. Most commonly, a person will first lose vision in one eye before losing vision in the other eye 2–3 months later.
During the atrophic phase, a person experiences damage to the optic nerve in both eyes, causing blindness.
Whether or not a person loses vision depends on the specific genetic variant they have. However, as many as half of male carriers lose vision, while most female carriers do not.
In extremely rare cases, a person may experience neurological abnormalities. These may include:
- peripheral neuropathy, or nerve damage in the hands and feet
- postural tremor, which is a tremor while deliberately holding a position against gravity, such as holding the arms outstretched
- nonspecific myopathy, or disorders causing muscle weakness
- movement disorders
People with asymptomatic (symptomless) LHON are unlikely to require constant monitoring from a doctor.
An ophthalmologists may diagnose LHON by conducting specialized vision tests.
No gold-standard clinical diagnostic criteria currently exist. However, a specialist can look for:
- painless vision loss in both eyes
- swelling in the retina or optic nerve
- broken blood vessels around the retina
- shrinkage and atrophy (wasting away) of the optic nerve
- optic nerve dysfunction with no other cause
Other signs unrelated to the eye that may occur include:
- neurologic abnormalities, such as postural tremors, peripheral neuropathy, movement disorders, and multiple sclerosis-like illnesses
- nonspecific myopathy
- irregular heart rhythm
An ophthalmologist can then confirm their findings with molecular genetic testing for the mitochondrial genes associated with LHON. However, many people will already know whether they have family members who are also carriers of LHON.
Doctors provide supportive management and treatment for people with LHON using:
- visual aids
- occupational rehabilitation
- local social services
Genetic variants in the mitochondrial DNA cause LHON. The three main LHON-causing mitochondrial DNA variants are:
Over 90% of people with LHON have one of these variants. While mt.11778G>A is the most common variant, mt.14484T>C is the most likely, and mt.14484T>C is the least likely, to cause vision loss.
Females with an LHON genetic variant may not experience symptoms. However, they will often have male relatives who have lost vision early on.
Mitochondrial DNA exists only in female eggs (none exists in sperm), so a person can only inherit a mitochondrial DNA mutation from a female parent.
On average, 50% of males and 15% of females with an LHON genetic variant will lose vision at some point during their lifetime.
A study in Frontiers in Neurology reported that people with mt.11778G>A have the most unfavourable outlook, with a 4% chance of recovering their lost vision.
Factors that can have a positive effect on outlook include developing LHON during childhood (as opposed to adulthood) and having the mt.14484T>C variant.
Additionally, one 2017 study from Denmark compared the incidence of comorbidities (having more than one disease at once) and mortality in people with LHON and unaffected family members against the general population.
The researchers found a relationship between LHON and increased mortality and an increased incidence of several health conditions, including:
People with LHON in the family should avoid smoking and drinking excessive amount of alcohol, if applicable. This is because these substances cause oxidative stress in the body, which can create or worsen DNA damage.
LHON is an inherited genetic condition that certain females can pass on to their children. The main symptom is vision loss that starts in one eye and gradually affects both eyes.
Males are four to five times more likely to experience vision loss than females. A person can help reduce the risk of mitochondrial damage that leads to vision loss by avoiding smoking and alcohol, if applicable.