HoG Handbook
 

The Inheritance of von Willebrand Disease

 

The gene for von Willebrand factor is on one of the autosomes, chromosome 12.  Since it is not on the sex chromosome, it occurs equally in men and women.

Types of VWD with Dominant Inheritance

Types 1, 2A, 2B, and 2M VWD have a dominant inheritance pattern.  This means that if a child gets a normal gene from one parent and a gene for one of these types of VWD from the other parent, the child will have VWD.  The VWD gene is stronger, or dominant, over the normal gene.

If only one of the parents has a dominant inheritance type of VWD, there is a 50% chance with each pregnancy that the child will have VWD.  Figure 3-3 shows the possible gene combinations for these autosomal dominant types of VWD.

If only one parent has a dominant inheritance type of VWD, with each pregnancy there is:

  • a 50% chance of having a child (boy or girl) who inherits the VWD mutation
  • a 50% chance of having a child (boy or girl) who does not inherit the VWD mutation.

With Type 1 VWD, sometimes a person can inherit the gene that causes a mutation but not have any symptoms of VWD.  This is called incomplete penetrance.

Figure 3-3.  An autosomal dominant inheritance pattern – the possible gene combinations with types 1, 2A, 2B, and 2M VWD.  The dominant gene is shown with a capital D.  A child will have the disorder if he or she inherits the dominant gene from either parent.

Figure 3-3 inheritance of vwd

Types of VWD with Recessive Inheritance

Type 2N and Type 3 VWD have a recessive inheritance pattern.  For Type 2N VWD, this means that if a child gets a normal gene from one parent and  a gene for Type 2N VWD from the other parent, the child will not have VWD.  He or she will be a carrier.  This is because the Type 2N gene is recessive – it is not stronger, or dominant, over the normal gene.  For the child to have Type 2N VWD, he or she must get an abnormal gene from both parents.

For a child to get Type 3 VWD, he or she has to get a VWD gene from both parents.  Usually the parents have the Type 1 VWD gene and may not even know they have it.

Figure 3-4 shows the possible gene combinations for these autosomal recessive types of VWD.

If both parents carry a defective recessive gene for VWD, with each pregnancy there is:

  • a 25% (one in four) chance of having a child who is unaffected
  • a 25% (one in four) chance of having a child who has VWD
  • a 50% chance of having a child who does not have VWD but carries the defective gene.

Figure 3-4.  An autosomal recessive inheritance pattern – the possible gene combinations with types 2N and 3 VWD and most platelet disorders.  The recessive gene is shown with a little r.  To have the disorder, a child must inherit a recessive gene from both parents.

Figure 3-4