Hemophilia is a genetic bleeding disorder characterized by the blood’s impaired ability to clot properly. This condition can lead to prolonged bleeding following injuries or even spontaneous bleeding. The body’s clotting process relies on proteins called clotting factors, and individuals with hemophilia have insufficient levels of specific factors, primarily factor VIII or factor IX.
Genetic Fundamentals
Genetic information is organized into structures called chromosomes. Humans have 23 pairs of chromosomes, with one pair, the sex chromosomes, determining biological sex. Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). Genes are specific segments of DNA located on these chromosomes, acting as instructions for producing proteins. Traits are determined by these genes. Certain genes provide the blueprint for creating the clotting factors necessary for blood coagulation. Hemophilia follows a specific inheritance pattern due to its location on sex chromosomes.
The X-Linked Recessive Pattern
Hemophilia A and B, most common forms, follow an X-linked recessive inheritance pattern. The genes responsible for producing clotting factors VIII (F8 gene) and IX (F9 gene) are on the X chromosome. Since males have only one X chromosome, if this chromosome carries an altered F8 or F9 gene, they will develop hemophilia because there is no corresponding gene on the Y chromosome to compensate.
Females, having two X chromosomes, are carriers of hemophilia. If one of their X chromosomes carries the altered gene, the other healthy X chromosome can produce enough functional clotting factor to prevent severe bleeding symptoms. Carrier females can pass the altered gene to their offspring. A carrier mother has a 50% chance with each pregnancy that her son will inherit hemophilia and a 50% chance that her daughter will also be a carrier. Hemophilia C, caused by a deficiency in Factor XI, is less common and is inherited differently, following an autosomal recessive pattern rather than X-linked.
Understanding Family Risks
Understanding hemophilia’s inheritance pattern has practical implications for families. Genetic testing is highly accurate in identifying female carriers by examining the F8 or F9 genes for specific mutations. This identification is important as some carrier females may experience bleeding symptoms themselves, ranging from mild to moderate.
Genetic counselors assist families in navigating these complexities. They provide comprehensive information about the condition, interpret genetic test results, and help families understand the likelihood of passing the disorder to future generations. This risk assessment allows families to make informed decisions regarding family planning and medical management. About one-third of hemophilia cases occur due to spontaneous new gene mutations (de novo) in individuals with no prior family history, demonstrating that not all cases are inherited from a parent.