What Causes Hemophilia / Haemophilia?

People with haemophilia are born with it. It is caused by a fault in one of the genes that determine how the body makes blood clotting factor VIII or IX. These genes are located on the X chromosome.

To understand how haemophilia is inherited, it is important to learn about chromosomes.


What are chromosomes?

Chromosomes are blocks of DNA (deoxyribonucleic acid). They contain very detailed and specific instructions that determine:

  • How the cells in a baby's body develop.
  • What features the baby will have, including, for example, hair and eye color.
  • Whether the baby is male or female.

In humans there are 23 pairs of chromosomes, including the sex chromosome pair. There are two types of sex chromosome:

  • The X chromosome
  • The Y chromosome
     

All humans have a pair of sex chromosomes:

  • Males have an X + Y pair
  • Females have an X + X pair NB  Females do not have any Y chromosomes.

What chromosomes do we inherit from our parents?

    A Male inherits his

  • X chromosome from his mother
  • Y chromosome from his father

    A Female inherits

  • One X chromosome from her mother
  • One X chromosome from her father. She does not inherit both X chromosomes from her mother. She has no Y chromosomes.


How can we calculate the risk of haemophilia in offspring?

Female (X + Xfaulty) is a carrier, but does not have haemophilia. The “good” X chromosome allows the production of enough clotting factor to prevent serious bleeding problems.
Male (Y + Xfaulty) will develop haemophilia and can pass it on.

If the father has haemophilia and the mother has no faulty gene (is not a carrier):

Father (Y + Xfaulty). Mother (X + X).

There is no risk of inherited haemophilia in their sons because boys will inherit their X chromosome from the mother, not the father (they inherit the father's Y chromosome only, which does not have the faulty gene).
All the daughters will be carriers but will not develop haemophilia although they will inherit the father's X chromosome, which has the faulty gene. However, their maternal X chromosome, which does not have the faulty gene, usually allows the production of enough clotting factor to prevent serious bleeding problems.

If the father does not have haemophilia and the mother has a faulty gene:
Father (Y + X). Mother (X + Xfaulty).

    There is a 50% chance that sons will develop haemophilia because:

  • There is a 50% risk that a son will inherit his mother's Xfaulty chromosome, plus his father's Y chromosome - he will have haemophilia.
  • There is a 50% chance he will inherit his mother's "good" X chromosome, plus his father's Y chromosome - he will not have haemophilia.

    There is a 50% chance that daughters will be carriers, (but no chance of developing haemophilia), because:

  • There is a 50% chance she will inherit her mother's Xfaulty chromosome, making her a carrier.
  • There is a 50% chance she will inherit her mother's "good" X chromosome, which would mean she would not be a carrier.

Approximately one third of patients with haemophilia have no family history of the disease, either because of new genetic mutations, or because previous affected generations either had daughters (who were carriers) or sons who died in early childhood from haemophilia or any other cause or who were not affected.