What Causes Hemophilia / Haemophilia?

People with hemophilia 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 hemophilia 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 hemophilia in offspring?

(Before reading on, remember that the faulty gene is never on the Y chromosome. If it is present, it will be on the X chromosome.)

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

If the father has hemophilia and the mother has no faulty gene (is not a carrier):
Father (Y + X_faulty). Mother (X + X).

• There is no risk of inherited hemophilia 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 hemophilia 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 hemophilia and the mother has a faulty gene:
Father (Y + X). Mother (X + X_faulty).

• There is a 50% chance that sons will develop hemophilia because:
  
  
  • There is a 50% risk that a son will inherit his mother's X_faulty chromosome, plus his father's Y chromosome - he will have hemophilia.
  • There is a 50% chance he will inherit his mother's "good" X chromosome, plus his father's Y chromosome - he will not have hemophilia.
• There is a 50% chance that daughters will be carriers, (but no chance of developing hemophilia), because:
  
  
  • There is a 50% chance she will inherit her mother's X_faulty 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 hemophilia 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 hemophilia or any other cause or who were not affected.