Why may your family members potentially be at risk of Fabry?

The genetics and inheritance of Fabry mean that it is possible you have family members with a Fabry mutation. 1 You may have had the mutation passed on to you from a parent, and it may have been passed on to others in the family as well. 1,2 In rare cases, the Fabry mutation is unique to the individual. 3

How is Fabry passed down in families?

Fabry is caused by genetic mutations located on the X chromosome. 2 Men and women can both be affected by Fabry, but the likelihood of a father or a mother passing down the Fabry mutation is not the same – it all depends on the chromosomes they pass on to their children. 4,5

What is a genetic mutation? 6
Genetic information is stored in DNA, providing instructions that tell every cell in your body what to do. Mutations can occur in DNA, these are errors in the instructions.

A mother affected by Fabry disease has a 50:50 chance of passing the Fabry mutation on to any of her daughters or sons: 1

  • This is because the mother has two X chromosomes, and either the X chromosome with the Fabry mutation or the X chromosome without the Fabry mutation could be passed on to her children

  • Which X chromosome is received is completely random, so it could be that a mother passes the Fabry mutation to all or none of her children, and any combination in between

A father affected by Fabry disease will pass the Fabry mutation on to all of his daughters but none of his sons: 1

  • This is because the father only has one X chromosome that must contain the Fabry mutation – his daughters will inherit this, but his sons won’t (they will inherit his Y chromosome)

Below is an example family showing all the possible people at risk of Fabry, if only the person who completed the tree (‘Me’) has a Fabry diagnosis.

The people highlighted in blue could have the Fabry mutation, but in reality, it is unlikely that they all will. As Fabry is rare and you only need one Fabry mutation to experience the disease, it is likely that only one side of your family will be affected, for example.

Here is an example of how Fabry could be passed down the generations of a family, starting with the maternal grandfather.

1. Laney DA & Fernhoff PM. J Genet Counsel. 2008:17:79-83 2. Germain D. Orphanet. J Rare Dis. 2010;5:30 3. Desnick RJ et al. Ann Intern Med. 2003;138(4):338-46 4. Laney DA, et al. J Genet Couns. 2013;22(5):555-564 5. How is Fabry Disease Inherited. National Fabry Disease Foundation. Available at: https://www.fabrydisease.org/index.php/about-fabry-disease/fabry-disease-inheritance [Last accessed February 2020] 6. DNA, genes, chromosomes and mutations. Genetic Alliance UK. Available at: https://www.geneticalliance.org.uk/information/learn-about-genetics/dna-genes-chromosomes-and-mutations/ [Last accessed August 2019]
Being highlighted as potentially at-risk is in no way a diagnosis of Fabry disease. Concerned individuals should speak to a healthcare professional.