How is hemophilia A inherited?
Fact-checked by Hemophilia A, the most common type of hemophilia, is a bleeding disorder that is inherited in an X-linked, recessive manner. This is because the F8 gene, which can cause hemophilia A when mutated, sits on the X chromosome. In addition, because hemophilia A is a recessive condition, it typically develops only when there is no healthy copy of the F8 gene to compensate for a mutated one.
This explains why the prevalence of hemophilia A is higher in males. As hemophilia A is caused by mutations in a gene found on the X chromosome, males will certainly have hemophilia A if they inherit a defective F8 gene because they have only one X chromosome. Females, on the other hand, have two X chromosomes, so if a female inherits a faulty F8 gene, she may still have a healthy gene copy on the other X chromosome to compensate for the mutated one. In that case, the female is said to be a carrier, meaning that while she may not experience hemophilia symptoms, she can still pass on the defective gene copy to her offspring.
Because of hemophilia A genetics, males inherit hemophilia A-causing mutations only from their mother, as she is the one passing on the X chromosome, whereas females can inherit an F8 gene mutation from either biological parent. A female may develop hemophilia A if she has two mutated F8 gene copies or if she has one healthy and one mutated gene copy, and the healthy copy is on the X chromosome that gets inactivated during a natural process that occurs during fetal development.
Inheritance probabilities
Put into percentages, if a female who is a carrier for hemophilia A has a child and the biological father does not have the disease, the odds include a:
- 50% chance that a male child will have hemophilia A
- 50% chance that a female child will be a carrier
In addition, if a female who is a carrier for hemophilia A has a child with a male who has the disease, the odds include a:
- 50% chance that a male child will have hemophilia A
- 50% chance that a female child will have hemophilia A, and a 50% chance that a female child will be a carrier
If a female who is not a carrier has a child with a male with hemophilia A, no male children will have hemophilia. But all female children will be carriers.
Spontaneous mutations
Although most cases of hemophilia A are inherited, the disease may also result from a spontaneous mutation in the F8 gene. This happens in about a third of all cases.
A spontaneous, or de novo, mutation arises in a parent’s egg or sperm cell or during the early stages of embryonic development, mainly due to random errors in DNA replication and cell division.
Once a person has a mutation in the F8 gene, they can pass it on to their children, even if the mutation arose de novo and was not inherited from either parent.
Carrier screening and genetic counseling
Carrier screening for hemophilia A, which uses a blood or saliva sample to test for a disease-causing mutation, may help females understand potential health risks and inform family planning decisions.
Females may be advised to undergo carrier screening if they have a family history of hemophilia A or if they have a child with the disease. Experiencing symptoms of hemophilia A is another potential reason to take a carrier screening test. In addition to being a definitive way to determine carrier status, this test may also help diagnose hemophilia A.
Genetic counseling may be important for families with a history of hemophilia A. By understanding how hemophilia A is inherited, a genetic counselor can help families understand the relevance of testing, who should be tested, and when. A genetic counselor can also help break down test results and what they may mean for future family planning decisions.
Reproductive options and pre-implantation testing
Women who have hemophilia A or are carriers for the disease should seek guidance from specialists if they are planning to have children. A multidisciplinary team with genetic counselors, hematologists, obstetricians, and anesthesiologists may be valuable for making family-planning decisions, discussing risks and treatment plans, and sharing information on the best strategies during pregnancy and delivery.
Hemophilia treatment centers may be key in taking these steps with greater confidence. They may provide useful information about prenatal tests, such as chorionic villus sampling or amniocentesis, which are invasive procedures used to identify genetic abnormalities in a developing fetus, including hemophilia A-causing mutations. Because male babies are more likely to have the disease, noninvasive prenatal testing may be used early in pregnancy to determine the sex of the baby and help decide whether invasive prenatal diagnostic tests should be considered.
Women and couples also have the option to screen embryos for hemophilia A-causing mutations before pregnancy. This is particularly important for women who are known disease carriers. When used in conjunction with in vitro fertilization, pre-implantation genetic testing can reduce the risk of passing on F8 mutations that could lead to hemophilia A.
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
