Hemophilia is a genetic bleeding disorder caused by a deficiency in clotting factors, most commonly Factor VIII (Hemophilia A) or Factor IX (Hemophilia B). This deficiency prevents blood from clotting effectively, leading to prolonged bleeding after injury or surgery. Understanding the inheritance pattern of this disorder requires examining the specific chromosomes involved in its transmission.
The Role of the X Chromosome in Inheritance
The genes for Factor VIII and Factor IX are located on the X chromosome, one of the two sex chromosomes. This location categorizes hemophilia as an X-linked recessive disorder. Females possess two X chromosomes (XX), while males have one X and one Y chromosome (XY). Because the Y chromosome does not carry a counterpart gene, a male needs only one copy of the defective gene to express the condition. Conversely, a female must inherit the defective gene on both X chromosomes to be fully affected, which is a rare occurrence.
Understanding Affected Individuals and Carriers
Hemophilia primarily affects males. If a male inherits the mutated X chromosome from his mother, he expresses the disorder because he lacks a second X chromosome to mask the recessive trait. The severity of his condition depends on the specific mutation, affecting how much functional clotting factor is produced.
Females who inherit one affected X chromosome and one healthy X chromosome are known as carriers. The healthy X chromosome usually produces enough clotting factor to prevent severe bleeding problems, meaning most carriers do not show the full effects of the disorder. However, many female carriers experience milder bleeding symptoms, such as easy bruising or heavy menstrual bleeding, due to lower factor levels.
A female can be fully affected if she inherits the gene from both an affected father and a carrier mother, or, more rarely, through skewed X-inactivation (Lyonization). In this phenomenon, the healthy X chromosome is disproportionately turned off, causing the faulty X chromosome to be the primary source of factor production. These symptomatic females may present with bleeding problems as severe as those experienced by affected males.
Predicting Inheritance: Transmission Scenarios
The X-linked recessive inheritance pattern allows for specific, predictable probabilities of transmission.
Carrier Mother and Unaffected Father
For a mother who is a carrier (XhX) and a father who is unaffected (XY), there is a 50% chance in each pregnancy that a son will inherit the faulty X chromosome and be affected by hemophilia. There is an equal 50% chance that a daughter will inherit the faulty X chromosome and become a carrier herself.
Affected Father and Unaffected Mother
When an affected father (XhY) has children with an unaffected mother (XX), none of their sons will be affected, because a father passes his Y chromosome to his sons. However, 100% of the daughters will inherit the father’s affected X chromosome, making all of them carriers of the condition.
Affected Father and Carrier Mother
The rarest scenario involves an affected father (XhY) and a mother who is a carrier (XhX). This is the only way a daughter can inherit two affected X chromosomes to be fully affected. In this case, there is a 50% chance that a daughter will be affected and a 50% chance that a son will be affected.