Genetics: how hereditary eye conditions are passed down

Many inherited eye conditions affect the retina and are known as inherited retinal dystrophies (IRDs). There is more information about IRDs in our factsheet ‘Understanding Retinitis Pigmentosa and Inherited Retinal Dystrophies’.

This page contains a summary of our information on how genetic eye conditions are passed down. To read our full information, download our factsheet via the following link:

DNA

DNA is genetic material found in our cells. It is found in the:

• cell nucleus - the control centre which manages how the cell works. This is called nuclear DNA.
• cell mitochondria – the ‘powerhouse’ of the cell (like a battery) which provides the energy needed for each cell to work. This is called mitochondrial DNA.

Genes

Genes are made of DNA and are present in every cell of our body. They provide the instructions needed for our cells to work correctly. If a gene is changed (a gene variant or mutation), the instructions it gives will be incorrect. This means the cells involved stop working as they should, causing a genetic condition.

Genes mostly come in pairs, meaning there are two copies of each gene in your cells. You inherit one copy from your biological mother and the other copy from your biological father.

When you become a parent yourself, you only pass on one copy of a gene to each of your children. Their other copy comes from their other parent.

Chromosomes

Chromosomes contain our genes. The majority of these chromosomes are not related to what sex you are, and they are known as autosomes. When genes on these chromosomes are passed on, it is called autosomal inheritance.

One pair of chromosomes determine whether you are born male or female. These chromosomes are named either X or Y. When an eye condition results from a gene change on these chromosomes, it generally involves the X chromosome. When those genes are passed on, it is called X-linked inheritance.

The way in which genes are passed on from one generation to another is known as the inheritance pattern. This can help us understand:

• who in your family has had the condition.
• the chances of your children inheriting the condition.

Eye conditions can be passed on in different inheritance patterns. They include:

• Autosomal dominant (AD) inheritance
• Autosomal recessive (AR) inheritance
• X-Linked (XL) inheritance
• Mitochondrial inheritance

Autosomal dominant (AD) inheritance

There is usually a known family history of autosomal dominant conditions. Some family members may be affected more than others.

Our genes come in pairs. Autosomal dominant inheritance means that:

• to have the condition, only one changed gene is necessary within a gene pair.
• this changed gene can be inherited from either parent.
• this parent usually has the condition also.

When a person with an autosomal dominant condition has a child,

• there is a 1 in 2 (50:50) chance their child will inherit the condition.
• there is a 1 in 2 (50:50) chance they will not inherit the condition.
• these chances are the same for both sons and daughters.

Autosomal recessive (AR) inheritance

Autosomal recessive conditions usually appear without any family history of the condition.

Our genes come in pairs. Autosomal recessive inheritance means that:

• to have the condition, both genes in a pair are changed.
• these genes are inherited from both parents who are ‘carriers’ of the condition.
• having one normal gene is enough to prevent the condition but make you a carrier.
• if you’re a carrier, your vision is usually unaffected.

When both parents are carriers of an autosomal recessive condition,

• there is a 1 in 4 chance that their child will inherit the condition.
• there is a 1 in 2 (50:50) chance their child will be a carrier of the condition.
• there is a 1 in 4 chance that the child will not inherit the condition and will not be a carrier.
• These chances are the same for both sons and daughters.

A parent who has an autosomal recessive condition will always pass on a changed gene to each of their children. However, this does not mean they pass on the condition. If the child’s other parent passes on a normal copy of the gene, their child will only be a carrier of the condition.

X-Linked (XL) inheritance

Within each of their cells, males and females have different sex chromosomes.

• males have an X and a Y chromosome
• females have two X chromosomes.

When a changed gene on the X chromosome is passed on, it is known as X-linked (XL) inheritance. X-linked conditions affect males and females differently, with males usually being affected more.

Males and X-linked recessive inheritance

• males have an X and a Y chromosome in each of their cells.
• a changed gene on their X chromosome means they will have the condition.

For a father who has an X-linked condition:

• his sons cannot inherit an X-linked condition from their father, and they will not become carriers of the condition.
• his daughters cannot inherit the condition from their father alone, but they can become carriers of the condition.

Females and X-linked recessive inheritance

• females have two X chromosomes in each of their cells.
• a changed gene on one X chromosome and a normal gene on the other means they’re a carrier of the condition.

For a mother who’s a carrier of an X-linked condition:

• there’s a 1 in 2 (50:50) chance each son will inherit the condition.
• there is a 1 in 2 (50:50) chance each daughter will be a carrier of the condition.

You can find out more information about these inheritance patterns by downloading our full factsheet:

No known relative and de novo inheritance

Some people with an inherited eye condition don’t know of any other members in their family with the condition. This may be because their relatives were carriers of the condition.

It may also be because the gene change happened spontaneously when the egg or sperm cell was formed, or shortly after conception. A spontaneous gene change like this is known as a ‘de novo mutation’. De novo inheritance means the genetic condition presents for the first time in that person, without being inherited from their parents. Genetic testing may be needed to identify which gene has changed. It’s unlikely that these parents will have another child with the same condition.

Mitochondrial inheritance

Some conditions are caused by a gene change in the mitochondria. The mitochondria contain their own DNA with 37 genes. Mitochondrial DNA is only passed on via the egg cell from our mothers (maternal inheritance).

Both males and females can have genetic changes in their mitochondrial DNA but for some conditions, more males go on to develop symptoms.

Genetic testing

Genetic testing can be carried out to:

• identify the specific gene change that is causing your condition.
• inform us how your vision may change over time and with what speed, though this is often difficult to predict
• show the inheritance pattern to show how likely it is for other members of your family to have the condition.
• show whether you could pass on the gene change to your children.

Many of the treatments being researched for inherited eye conditions rely on knowing the specific gene change. Knowing which gene is involved is important for the potential of future treatment.

There are several genetic centres around the country that carry out genetic tests. The service is provided free on the NHS if your ophthalmologist or your GP refers you.

Genetic counselling

Genetic counselling aims to provide the information you need to understand your inherited condition. It can also enable you to make informed decisions relating to your condition.

Genetic counsellors are specialists in genetics and counselling. They work in genetic centres to offer you support around your test results. Genetic counselling can be invaluable even before genetic testing is carried out. It may prepare you for your results and what they may potentially mean for you.

Genetic counselling is a free service within the NHS. To access this service, you can ask your GP or ophthalmologist to refer you.

• Gene Vision - a resource on rare genetic eye disorders for everyone
• ROAM (Research Opportunities at Moorfields) - get involved in research
• Genetic Alliance
• Retina UK
• LHON Society