Ataxia is caused by damage to the spinal cord and a part of the brain known as the cerebellum. The spinal cord is a cable of nerves that runs from the brain to the rest of the body.
The cerebellum sits at the base of the brain (the brainstem) and is responsible for controlling:
- physical movement,
- co-ordination, and
- spatial awareness (awareness of your surroundings in the relation to yourself).
In cases of acute ataxia, the spinal cord and cerebellum can be damaged by factors such as:
- physical trauma,
- infection, and
- loss of blood supply.
In cases of hereditary ataxia, the spinal cord and cerebellum are damaged slowly, over time, as the genetic mutations that are associated with hereditary ataxia interfere with the normal development of the brain and nervous system. This leads to progressive brain and neurological damage.
Different mutations can affect the brain and nervous system in different ways, but what they usually have in common is that they interfere with the normal production of proteins which results in damage to nerve cells.
For example, Friedreich’s ataxia is caused by a mutation in a gene known as the GAA gene. This mutation results in the body not producing enough of a protein called frataxin. Frataxin is thought to play a role in the regulation of iron levels inside nerve cells.
As not enough frataxin is being produced, the level of iron and other toxic substances starts to build up inside the nerve cells, damaging them.
The genetics of ataxia
In order to gain a better understanding of the genetics of hereditary ataxia, it is useful to learn about chromosomes.
Chromosomes are blocks of deoxyribonucleic acid (DNA). They contain a detailed set of instructions that control a wide range of factors - from how the body’s cells develop, to what colour eyes a baby will have, and what sex a baby will be.
You receive two sets of chromosomes - one from your mother and one from your father. As all the genes in your body are created from these chromosomes, you will receive two sets of every gene - one gene from your mother and one gene from your father.
There are two ways that a genetic mutation can be passed down through families:
- autosomal recessive - such as the mutation that is responsible for Friedreich’s ataxia , and
- autosomal dominant - such as the mutation that is responsible for spinocerebellar ataxia.
Autosomal recessive
If the mutated gene is autosomal recessive, it means that you will only develop ataxia if you receive a pair of mutated genes (one from your mother and one from your father).
If you only receive one of the mutated genes, the other normal gene will ‘cancel out’ the effects of the mutation. However, you will be a carrier of one of the mutated genes. It is estimated that 1 in every 80 people are carriers of a mutated ataxia gene.
If two carriers have a baby:
- there is a 25% chance that the baby will receive a pair of normal genes,
- there is a 50% chance that the baby will receive one normal gene and one mutated gene; in this case, they will not develop ataxia, but they will be a carrier, and
- there is a 25% chance that the baby will receive a pair of mutated genes and will develop ataxia.
If you have autosomal recessive ataxia, and your partner is a carrier:
- there is a 50% chance that your baby will receive one normal gene and one mutated gene and become a carrier, and
- there is a 50% chance that your baby will receive a pair of mutated genes and develop ataxia.
If you have autosomal recessive ataxia and your partner is not a carrier, there is no risk that any children that you have will develop ataxia because your mutated gene will be cancelled out by your partner’s normal gene.
Autosomal dominant
If the mutated gene is autosomal dominant, you can develop ataxia if you receive a single mutated gene, either from your mother or your father. This is because the mutation is strong enough to ‘override’ the other, normal gene.
If you have autosomal dominant ataxia, any children that you have will have a 1 in 2 chance of developing ataxia.
Genetics and pregnancy
There are a number of tests that can be used to check whether your partner is a carrier of any of the autosomal recessive ataxia genes, so that you can better estimate the risk of having a baby with ataxia.
Testing should also be able to detect if a pregnancy will result in the baby being born with autosomal dominant ataxia. These types of tests are known as genetic counselling.
Your GP should be able to arrange for you to be referred to a regional genetic centre where counsellors will be able to carry out the tests and explain the implications of the results to you.
Alternatively, the Genetics Interest Group (GIG) provides information about the genetic services that are available in England.
