Inheritance

In most cases Haemophilia is an inherited condition and is passed down through family genes. However, it is possible for the condition to appear in any family (known as a spontaneous mutation). It is thought that at least 30% of people with haemophilia have no family history of a bleeding disorder. It is difficult to be exact about this because of the way in which haemophilia is inherited.

Haemophilia has a sex-linked recessive inheritance pattern. Sex-linked means that the gene that affects haemophilia is located on the genes that are connect with determining the sex of the child. Recessive meaning it usually only has an impact when gene is inherited from both parents . In the case of haemophilia, it means something slightly different as explained below.

Generally, males are affected by moderate or severe haemophilia. In rare cases, women can also get these forms, but it is more common that they have mild or normal levels for clotting factor. Anyone with the haemophilia gene is technically a “carrier” (a person who has the deficient gene). The term carrier is more often used for women who have the gene and a normal factor level. If a woman has a factor level less than 40%, then she is someone who has a form of haemophilia and is a carrier.

How does this it work?

In genetics, a male is someone with a “X” and a “Y” chromosome pair (a bundle of genes). A female is someone with a “X” and a “X” chromosome pair. A child will take either a “X” or “Y” from their father and take either a “X” or “X” from their mother. The haemophilia gene is only on the X chromosome and is not on the Y. As a result, haemophilia is passed on through the female member of the family.

Examples:

Father with haemophilia gene

When the father has the haemophilia gene, but the mother does not, none of their sons will have haemophilia gene, because to have a boy would mean getting a Y from the father, which doesn’t pass on the haemophilia gene. The sons will not be affected by haemophilia, nor will they be carriers of the gene.

However, all of their daughters will be “obligate” carriers, as the only X a female child can receive from their father has the haemophilia gene. The other X the female child receives from their mother has a normal haemophilia gene.

Figure 1: When the father has haemophilia and the mother is unaffected. None of the sons will have haemophilia. All of the daughters will carry the haemophilia gene.

Mother with haemophilia gene

Being a woman with the haemophilia gene, means that one of her “X” chromosomes carry the haemophilia gene. This can come directly from a father with the haemophilia gene or even through multiple generations of women. If the mother has the haemophilia gene on one of her X chromosomes, then there is a 50% chance that she will pass on a X chromosome without a haemophilia gene to her child and 50% chance she will pass on a X with the haemophilia gene to her child. So, whether the child is male or female, there is a 50% chance that they will carry the haemophilia gene.


The other concept that is important is “lyonsiation”. In males, they receive one X and one Y. In females they receive two X’s. To stop female cells from having twice as many gene products from the X chromosomes as males, one copy of the X chromosome in each female cell is inactivated. In haemophilia, usually the X that has the haemophilia gene is inactivated and as a result is called “recessive”. However, in some rare cases, the normal X chromosome is inactivated instead and the result is a girl with the haemophilia gene who may have severe haemophilia as both X chromosomes are now affected.


It is also possible for a girl to have severe haemophilia if her father is a person with haemophilia and her mother is a carrier.

Figure 2: When the mother carries the haemophilia gene and the father is unaffected. There is a 50% chance at each birth that a son will have haemophilia. There is a 50% chance at each birth that a daughter will carry the haemophilia gene.

If you would like to talk to somebody about the inheritance of haemophilia, please contact the Society office