Each
cell of the body contains structures called chromosomes. A chromosome is
a long chain of chemicals known as DNA. This DNA is arranged into
hundreds of units called genes which determine such things as the colour
of a person's eyes.
Each cell contains 46 of these
chromosomes arranged in 23 pairs, one of which is known as the sex
chromosome because it determines the sex of the person. Females have two
X chromosomes in this pair; males have one X and one Y.
Figure 3 illustrates the heredity
pattern for the sex chromosomes. The mother, who has two X chromosomes,
produces an egg containing one X chromosome. The father, who has one X
and one Y chromosome, produces sperm which could contain either an X or
a Y chromosome. If the father contributes his X, a girl is conceived. If
he contributes a Y, a boy is conceived.
How is hemophilia passed on from one generation
to the next?
The genes responsible for producing Factor VIII and
IX, the mutant genes in hemophilia, are situated on the X chromosome.
This makes hemophilia a sex-linked genetic disorder.
Figure 4 shows what happens when
a hemophiliac male has a child with a normal female.
All the daughters will be
carriers of hemophilia since they must inherit the X chromosome which
carries hemophilia from the father. All sons will be unaffected by
hemophilia since they inherit the father's normal Y chromosome.
Figure 5 shows the heredity
pattern when a normal male has a child with a female carrier of
hemophilia.
If they have a son, he has a 50%
chance of having hemophilia. This is determined by which X chromosome he
inherits. If he inherits the mother's normal X chromosome, the boy will
not have hemophilia. If he inherits the mother's mutated X chromosome,
he will.
In the same way, the couple's
daughter has a 50% chance of being a carrier. She could inherit the
mother's normal X chromosome, and be normal herself. On the other hand,
she could inherit the mother's X chromosome carrying the hemophilia
defect and be a carrier.
Can carriers have hemophilia?
Because carriers
have one normal X chromosome which produces a certain amount of Factor
VIII or IX clotting factor, they are protected from the most severe form
of hemophilia in which the level of clotting factor is less than 1%.
However, the variation in
clotting factor levels in carriers is very wide. It ranges from levels
similar to those of hemophiliacs in some carriers to normal levels in
others. This is because the two X chromosomes, one of which carries the
hemophilia gene, are not equally functional. If the hemophilia X
chromosome happens to be functional in most cells, then the carrier will
have a very low level of clotting factor activity.
Many carriers have a clotting
level between 30% and 70% of normal and do not usually suffer from
excessive bleeding. However, some carriers have less than 30% of the
normal level of Factor VIII or IX. These women are considered to be mild
hemophiliacs.
In any case, all carriers should
pay close attention to signs of abnormal bleeding. These signs include:
heavy, prolonged menstrual
bleeding (menorrhagia)
easy bruising
frequent nose bleeds.
Is there always a history of hemophilia in the
family?
No. There are
several explanations for a boy being born with hemophilia when there is
no history of hemophilia in the family.
Figure 6 shows the family pattern
when a hemophiliac boy is born to a mother who is not known to be a
carrier.
It is estimated that up to 30% of
cases of hemophilia have no known family history. Many of these cases
are the result of new mutations. This means that hemophilia can affect
any family.
Because sisters and mothers of
hemophiliacs are not necessarily carriers, as seen in Figures 5 and 6,
it is important to do hemophilia carrier testing.
What tests are done to find out if a woman is a
carrier?
