Key points
- Most cases of hemophilia are inherited (passed down) from a parent to a child.
- Because hemophilia genes are passed down on the X chromosome, males with hemophilia are much more likely to have serious bleeding symptoms than females.
- Because the genes affected in hemophilia are located on the X chromosome, bleeding symptoms in females with hemophilia are usually milder than those in males with hemophilia. Nonetheless, hemophilia has been found to have measurable impacts on joint mobility in females.
What causes hemophilia?
Hemophilia is a bleeding disorder in which blood does not clot properly. Blood contains many proteins called clotting factors. Clotting factors can help to stop bleeding after injury or surgery. People with hemophilia have low amounts of either factor VIII (8) or factor IX (9). Factor VIII and factor IX are key factors responsible for normal blood clotting.
A person's genes provide the instructions on how to make proteins, such as factor VIII and factor IX. In people with hemophilia, there is a mutation (difference from normal) in either the gene for the factor VIII protein or the gene for the factor IX protein. The mutation causes the body to produce too little factor VIII or IX. This change in a copy of the gene making factor VIII or factor IX is called a hemophilia allele.
Most people who have hemophilia are born with it. It is inherited (passed down) from a parent to a child. Nonetheless, about one third of babies who are diagnosed with hemophilia have no other family members with the disorder.
Types of hemophilia
X chromosome inheritance
Both hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are inherited in the same way, because both the genes for factor VIII and factor IX are located on the X chromosome (chromosomes are structures within the body's cells that contain the genes).
The X and Y chromosomes determine whether a person's sex is male or female. Females have two X chromosomes (XX), and males have one X chromosome and one Y chromosome (XY). There are no genes for clotting factors on the Y chromosome. This means that males only have one allele for factor VIII and one allele for factor IX. Thus, if a male has a hemophilia allele on his only X chromosome, he will have the disorder.
A female inherits two copies of the factor VIII or factor IX gene, one from her mother and one from her father. A female with a hemophilia allele on one X chromosome usually has a normal allele on her other X chromosome that can produce normal clotting factor. The normal allele provides some protection against having hemophilia.
A female with one hemophilia allele and one normal allele is called heterozygous, or a carrier. Some girls and women who are heterozygous have bleeding symptoms. While bleeding symptoms in females are usually milder than those in males with hemophilia, in rare cases, a female who is heterozygous can have bleeding symptoms that are as serious as those of a male with hemophilia.
A female can also have hemophilia if (a) she inherits hemophilia alleles from both of her parents or (b) if she inherits one hemophilia allele and her other X chromosome is missing or does not work properly. Females with these types of inheritance patterns are as likely as males with hemophilia to have severe bleeding symptoms.
Because most females who inherit hemophilia are heterozygous and have no bleeding symptoms or mild bleeding symptoms, hemophilia may be hidden in a family for many generations if it passes only through females.
If a mother is heterozygous for hemophilia and the father does not have hemophilia, each son has a 1 in 2 (50%) chance of getting his mother's hemophilia allele and having hemophilia. Each daughter has a 1 in 2 (50%) chance of getting her mother's hemophilia allele and being heterozygous. Overall, there is a 1 in 4 (25%) chance for each pregnancy that the baby will be a son with hemophilia and a 1 in 4 (25%) chance that the baby will be a heterozygous daughter. There is a 1 in 2 (50%) chance that the baby (either a son or a daughter) will not get the hemophilia allele at all and, therefore, can't pass it down to his or her children.
A father who has hemophilia passes his only X chromosome down to all of his daughters. The daughters will always get his hemophilia allele and be heterozygous. A father passes down his Y chromosome to his sons. Fathers cannot pass down a hemophilia allele to sons. Without the hemophilia allele, the sons will not have hemophilia and can't pass it down to their children.
Overall, there is a 1 in 2 (50%) chance that the child of a father who has hemophilia will be a son who does not have hemophilia and a 1 in 2 (50%) chance that the child will be a daughter who is heterozygous (a carrier). This is true if the mother does not have a hemophilia allele herself. That would be very rare.
