Trait Document

Leber Hereditary Optic Neuropathy (LHON) is a rare genetic condition in which individuals, often in their teens to 20s, develop blurred vision, usually starting in one eye and progressing to the other eye within two to three months. Optic Neuropathy refers to damage of the optic nerve. The optic nerve relays what the eye sees to the brain.

Vision loss for most individuals reach legal blindness (20/200). Significant improvement in vision is rare. In most cases, LHON only affects the eyes. However, other symptoms have been reported to be more common in some individuals with LHON than in those without LHON. These other symptoms can include cardiac arrhythmia (irregular heartbeat), postural tremor (unintentional rhythmic muscle movement of a body part occurring when a person maintains a position against gravity), peripheral neuropathy (weakness, numbness, and pain in arms and legs), myopathy (muscle weakness), and movement disorders.

Most individuals with LHON have a change or mutation in their mitochondrial DNA. However, males are more likely than females to be affected. The mitochondrial DNA mutations that cause LHON show reduced penetrance. Penetrance refers to the proportion of people with a particular genetic mutation who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced penetrance. For LHON, approximately 50% of males with a mutation will develop vision loss, while only 10% of females with a mutation will develop vision loss.

Clinical diagnosis of LHON is based on findings on an ophthalmology exam. Testing includes photography of the back of eye, visual field tests to determine the field of vision and identify any blind spots, and other specialized tests to measure the health of the eye.

Management of LHON often includes the use of low vision aids. Individuals with LHON should moderate their alcohol intake and avoid smoking.

LHON is due to mutations in the mitochondrial DNA. Mitochondria are structures inside the cells that are responsible for generating the energy that is needed to perform daily activities. Humans also carry DNA in mitochondria, and mutations in mitochondrial DNA can result in LHON.

Humans inherit mitochondria only from their mothers. Therefore, in maternal mitochondrial inheritance, the affected mitochondria are passed from mothers (who may or may not show symptoms) to children of either sex. Because males do not transmit mitochondria, a male with a maternal mitochondrial disorder generally cannot pass it to his children. Mitochondrial DNA mutations can also occur brand new (de novo) in an affected individual. When de novo, parents and siblings of an affected person are not at increased risk, but if the affected person is a female, her children are at increased risk.

Inside each cell, there is a mixture of mutated mitochondrial DNA and normal mitochondrial DNA. Symptoms are more likely when the mixture contains more mutated mitochondrial DNA. The number of mitochondria with mutated versus a normal mitochondrial DNA is variable across different body tissues (blood, brain, heart, skin, hair, etc.). Moreover, the number of mutated versus normal mitochondrial DNA can change dramatically when passed from mothers to their children.

Maternal mitochondrial inheritance is associated with a significant degree of variability. Because of this remarkable variability, it can be difficult to provide inheritance risk estimates for people with a maternal mitochondrial condition; however specific information may be available depending on the identified mitochondrial DNA mutation.

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