LHON is an inherited form of vision loss. This means that it is passed down in families through genetic information. LHON is caused by a genetic mutation in mitochondria (part of the cell that produces energy) that is passed down to you by your mother. These mutations can stop your mitochondria from functioning properly. In LHON, this can cause certain cells, called retinal ganglion cells (RGCs), to stop working. RCGs not working properly will lead to central vision loss and other visual symptoms of LHON.
Genetics of LHON
LHON is inherited through genetic information from mitochondria. This genetic information is called mitochondrial DNA (or mtDNA). You can find out more about mitochondria and mitochondrial diseases by clicking here.
In LHON, genes within the mitochondrial DNA are changed. In genetics, this is called a mutation and the changed mtDNA is referred to as mutant mtDNA. In contrast, mitochondrial DNA that is not changed is called wild type mtDNA.
It is typical for someone with a LHON mutation to only have mutant mtDNA. They would then be described as homoplasmic. However, in about 1 in 7 cases someone is heteroplasmic, which means they have a mixture of both wild type and mutant mtDNA.
Those who have lost their central vision due to LHON are often referred to as affected. Those with a LHON mutation gene but without vision loss are known as carriers.
How is LHON inherited?
LHON is passed to children by mothers with mutant mtDNA. This is because only egg cells contribute mitochondria to a developing embryo during pregnancy. This is called maternal inheritance. If a mother has one of the LHON mitochondrial genetic mutations, then so will all her children. LHON cannot be passed down by fathers.
Genetic testing can tell if you have mutant mtDNA, and therefore a carrier of LHON. Unfortunately, it cannot predict when symptoms will develop, how severe they will be or how quickly symptoms will progress. It also cannot predict how much mtDNA will be passed on from heteroplasmic mothers.
About 4 in 10 people affected (40%) do not have a clear family history of LHON.
How do the genetic mutations affect vision?
In LHON, the mitochondria in certain cells in your eye (called retinal ganglion cells) are affected by genetic mutations. This causes the cells to stop working or die. Because these cells are needed to send visual information from the eyes to the brain (the optic nerve), when they stop working your vision gets worse. This is what leads to the central vision loss and other visual symptoms of LHON. For more details about these symptoms, visit the section ‘What are the symptoms of LHON?’.
You can carry a mitochondrial DNA mutation without experiencing any signs or symptoms of vision loss. This makes it hard to predict which members of a family who carry a mutation will eventually become affected. However, it is important to realise that most people do not go completely blind, and your peripheral vision often allows you to lead an independent life.
Different LHON mutations
LHON is the most common mitochondrial condition and about 45 mutations have been linked to LHON. However, most LHON cases (over 90%) are caused by 1 of 3 mutations.
The most common is the mutation known as the 11778 (G11778A) mutation. This accounts for about half of all LHON cases.
The next most common mutations are 14484 (T14484C) or 3460 (G3460A) mutations.
In some rare cases, patients can experience a significant recovery of vision, and this is more likely to happen if you have the 14484 mutation.
Some of the rarer LHON mutations include: