Genetics

Aniridia is a genetic condition and in almost all cases is caused by a fault in a particular gene,  known as the PAX6 gene. This gene plays a large role in the development of the eye and may also play a role in the development of other parts of the body including the brain.

Every person has two copies (alleles) of each gene in their DNA. One is inherited from their father and one is inherited from their mother. Sometimes a mutation can occur in a gene. This is where a mistake occurs in the DNA structure of the gene.  The result is either that the gene does not work properly or does not work at all. Mutations are natural frequent and random. Aniridia occurs  when a person has one normal copy of the PAX6 gene and one damaged (mutated) copy.

In cases where a child is born with aniridia but there is no history of aniridia in the family it is referred to as sporadic aniridia. This simply means that a random mutation occurred when the baby was conceived. The baby has not inherited the condition from either of their parents.

If one parent already has aniridia they have one normal PAX6 gene and one faulty PAX6 gene. When they have a baby it is 50/50 which copy of the gene they will pass on. The baby will inherit a normal PAX6 gene from the other parent. This means the baby will have a 50% chance of having aniridia depending on which gene it inherits from the parent with aniridia. If a parent and baby have aniridia then this is referred to as inherited or familial aniridia.

In the very rare case where both parents have aniridia, any children they had would have:

  • 25% chance of inheriting two normal copies of the PAX6 gene and not having aniridia,
  • 50% chance of inheriting one normal and one faulty copy of the PAX6 gene and having aniridia,
  • 25% chance of inheriting two faulty copies of the gene.
    Such a foetus would be expected to be abnormal and die perinatally (up to 5 months before or 1 month after birth). The abnormality would be readily detected in ultrasound scans by 20 weeks and perhaps earlier if the clinician is specifically aware of the possibility.

Aniridia is described as having dominant inheritance because a person only needs one faulty copy of the PAX6 gene to have some symptoms of aniridia. There are other genetic disorders which have recessive inheritance. This means a person has to have two faulty copies of a particular gene to show any symptoms. People with only one copy would be perfectly healthy but would be carriers of the condition. If two carriers had a child together then there is a chance the child could inherit two faulty genes and be affected by the condition.

It was once thought that there were two forms of aniridia, one dominant and one recessive. With advances in genetics it has been proven that almost everyone with aniridia has a PAX6 mutation and this is always a dominant trait. This means aniridia cannot skip generations in a family, however some people can have very mild symptoms. They may even having an iris which looks almost normal, but there are subtle signs of aniridia which can only be observed using a microscope to examine the eye.

A person with a damaged PAX6 gene may also have other neighbouring genes which are damaged too. This can lead to set of more complex medical conditions known as WAGR syndrome. Aniridia is often the most obvious symptom of WAGR so it is normal for babies with aniridia to have genetic testing to establish their risk of developing other symptoms of WAGR, particularly Wilms’ tumor.

Adults with aniridia can also have genetic testing/counselling if they wish, most commonly because they are hoping to start a family and want to understand the implications for their baby.

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