How is Hemophilia Inherited?
Hemophilia is a hereditary disorder that affects the blood's ability to clot properly. Hereditary means that hemophilia can be passed down from generation to generation—parent to child—in what is called a sex-linked recessive pattern. This process explains why boys primarily develop symptoms of hemophilia, while girls are generally carriers of the disorder.
Hemophilia is in the Genes
Hemophilia is caused by a mutation (or abnormality) in the gene that controls the body's production of one of the factor proteins involved in blood coagulation (clotting). Hemophilia is a sex-linked recessive disorder because these genes are located on the X chromosome. Remember, the X chromosome is one of a pair of two chromosomes that determines a person's sex-XX for females and XY for males. "Recessive" means that the mutated gene is expressed—that is, causes symptoms—only when its pair is also mutated or missing.
Is it true that only males get hemophilia? This is almost always true. Males are much more likely to get the disorder, because they only have one X chromosome, which they receive from their mother; their other sex chromosome is a Y received from their father. Therefore, the mutated X gene is expressed because it is missing its normal counterpart.
On the other hand, because a female has two X chromosomes, even if one of them has the mutation, if the other one is normal it will protect her from the severe form of hemophilia. For a female to have symptoms of hemophilia, she would generally have to have two mutated X chromosomes, received from both her mother and father—and this scenario is very rare.
Some females with one mutated gene may have more bleeding than a normal person. However, most females with one normal X and one mutated X chromosome are only carriers. This means they are not affected by symptoms of the disorder, but they carry the gene mutation and can pass it on to their children.
The Chances of Passing on Hemophilia
There are several scenarios by which hemophilia may be passed on in families. If a woman is a carrier of the hemophilia gene—meaning she has one normal and one mutated X chromosome—and a man has no hemophilia gene, their son will have a 50/50 chance of developing the condition. This is because he will always receive a Y chromosome from his father—but he has a 50% chance of inheriting the normal X chromosome and a 50% chance of inheriting the mutated X chromosome from his mother. The daughter of this couple will not have hemophilia, but she has a 50% chance of receiving the mutated gene from her mother, thereby being a carrier as well.
When a man with hemophilia has children with a woman who does not carry the hemophilia gene, none of their sons will have hemophilia because the father passes along his normal Y chromosome to them and the mother passes a normal X. However, because the father passes his abnormal X chromosome to all his female offspring, this couple's daughters will all be carriers. The following illustration shows these scenarios:
The Genetics of Hemophilia
- Unaffected Father
- Carrier Mother
- Unaffected Son
- Unaffected Daughter
- Carrier Daughter
- Affected Son
- Unaffected
- Affected
- Carrier
A girl can be born with severe hemophilia only when:
- A woman who is a carrier has a child with a man who has hemophilia—so both pass on a mutated X chromosome.
- A woman who is a carrier has a child with a normal man AND a second new spontaneous hemophilia mutation happens when the child is conceived.
- A man who has hemophilia has a child with a normal woman AND a second new spontaneous hemophilia mutation happens when the child is conceived.
These three situations are extremely rare.