Hemophilia

Hemophilia A and B are both caused by a genetic defect present on the X chromosome (hemophilia C is inherited in a different fashion). About 70% of all individuals with hemophilia A or B inherited the disease. The other 30% have hemophilia because of a spontaneous genetic mutation.

In order to understand the inheritance of these diseases, a brief review of some basic human genetics is helpful. All humans have two chromosomes which determine their gender: females have XX, males have XY. When a trait is carried only on the X chromosome, it is called sex-linked.

Because both factors VIII and IX are produced by direction of the X chromosome, hemophilia A and B are both sex-linked diseases. Because a female child always receives two X chromosomes, she nearly always will receive at least one normal X chromosome. Therefore she will be capable of producing a sufficient quantity of factors VIII and IX to avoid the symptoms of hemophilia. If, however, she has a son who receives her flawed X chromosome, he (not having any other X chromosome) will be unable to produce the right quantity of factors VIII or IX, and he will suffer some degree of hemophilia.

In the rare event of a hemophiliac father and a carrier mother, the right combination of parental chromosomes will result in a hemophiliac female child. This situation, however, is extraordinarily rare. The vast majority of individuals with either hemophilia A or B, then, are male.

As mentioned earlier, about 30% of all individuals with hemophilia A or B are the first members of their families to ever present with the disease. These individuals had the unfortunate occurrence of a spontaneous genetic mutation, meaning that early in development, some random genetic accident befell their X chromosome, resulting in the defect causing hemophilia A or B.