Hemophilia is a genetic bleeding disorder where blood does not clot properly due to insufficient levels of specific blood proteins called clotting factors. When these factors are missing or reduced, even minor injuries can lead to prolonged bleeding. As an inherited condition, hemophilia is passed down through families. This article explores its genetic foundations and inheritance patterns.
The Building Blocks of Inheritance
Our bodies are composed of countless cells, and within each cell’s nucleus are structures called chromosomes. Chromosomes are thread-like structures that contain our genes, which are segments of DNA carrying instructions for making proteins. Humans typically have 23 pairs of chromosomes.
One pair of these chromosomes, the sex chromosomes, determines an individual’s biological sex. Females typically have two X chromosomes (XX), while males typically have one X and one Y chromosome (XY). Genes located on the X chromosome are important in conditions like hemophilia. In hemophilia, an altered gene responsible for producing a clotting factor, such as Factor VIII or Factor IX, leads to a faulty or insufficient protein.
How Hemophilia Genes are Passed Down
Hemophilia A and B, the most common forms, are inherited in an X-linked recessive pattern. The genes responsible for Factor VIII (Hemophilia A) and Factor IX (Hemophilia B) are located on the X chromosome. Because males have only one X chromosome, inheriting an altered gene on it is sufficient for them to develop hemophilia, which explains why these forms predominantly affect males.
Females, with two X chromosomes, can be “carriers” of hemophilia. A carrier female has one X chromosome with the altered gene and one normal X chromosome. The normal gene usually provides enough clotting factor to prevent severe bleeding symptoms, though some carriers may experience milder symptoms. When a mother is a carrier, each of her sons has a 50% chance of inheriting the altered gene and developing hemophilia. Each daughter has a 50% chance of becoming a carrier herself.
If a father has hemophilia, he will pass his only X chromosome to all of his daughters, making all of them carriers. However, a father with hemophilia cannot pass the altered gene to his sons, as sons inherit their X chromosome from their mother and their Y chromosome from their father.
When Hemophilia Appears Unexpectedly
While most hemophilia cases are inherited, approximately one-third of individuals with hemophilia A or B have no prior family history. In these instances, hemophilia arises due to a “spontaneous mutation” in the gene responsible for the clotting factor. This new genetic alteration occurs randomly and can be passed on to a child.
Hemophilia C, caused by a deficiency in Factor XI, presents a different inheritance pattern. Its gene is located on an autosome. Hemophilia C is inherited in an autosomal recessive manner, meaning an individual must inherit two copies of the altered gene—one from each parent—to develop the condition, affecting males and females equally.
Genetic Counseling and Family Planning
Genetic counseling helps individuals and families navigate hemophilia. These services provide information about the condition, its inheritance patterns, and implications for family members. Genetic counselors help individuals understand their risk of being a carrier or having a child with hemophilia, especially for those with a family history or carrier females considering children.
Genetic testing identifies specific gene alterations and determines carrier status. This information empowers individuals to make informed decisions regarding their health and family planning. Counselors discuss various options, including prenatal diagnosis, which can identify the condition in a fetus.