Von Willebrand disease inheritance patterns

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VWD is a bleeding disorder that people typically get by inheriting a genetic variant from their parents. A person can inherit VWD if one of their parents has this condition or if both parents carry a gene for VWD.

Is VWD dominant or recessive?

Everyone has two copies of each gene, with one coming from each parent.

If a condition is autosomal dominant, it means a person needs to inherit only one copy of the gene that causes that condition, from one of their parents. If a condition is autosomal recessive, it means a person will develop the condition only if they inherit two copies of the gene — one from each parent.

VWD can have either an autosomal dominant or an autosomal recessive inheritance pattern.

What is the most common inheritance pattern?

The most common inheritance pattern in VWD is the autosomal dominant pattern.

The way people inherit VWD influences the type of VWD they develop. Doctors categorize VWD into three types:

• Type 1 VWD: This is the most common form, affecting about 70% of people with VWD. It is usually mild and can cause spontaneous or mild bleeding in the skin and mucous membranes.
• Type 2 VWD: This accounts for about 15% of cases of VWD and has four subtypes:
  • Type 2A: This type can cause mild to moderate bleeding, as the VWF is not the right size to help platelets stick together and form a clot.
  • Type 2B: In this type, VWF attaches to platelets at the wrong time, when there is no injury. This can cause a low platelet count.
  • Type 2M: VWF attaches the platelets in the wrong way, making it more difficult to form a clot.
  • Type 2N: VWF attaches to the platelets typically, but it does not attach to factor VIII, another protein that is also necessary for blood clotting.
• Type 3 VWD: This is the rarest form of VWD, affecting about 3% of people with the condition. It can cause severe skin and musculoskeletal bleeding.

Most people with type 1 or type 2 VWD inherit the condition via an autosomal dominant pattern. This means only one of their parents needs to carry a VWD gene for them to potentially inherit the condition and develop symptoms.

Type 3 VWD is usually autosomal recessive, meaning that both parents need to provide a copy of a VWD gene in order for their child to develop the condition. A small number of type 2 and type 1 cases are also autosomal recessive.

People have different chances of inheriting VWD at birth depending on the type and prevalence of VWD in their parents.

Type 1 and 2

For most cases of types 1 and 2, there is a 50% chance of a child having VWD if one of their parents carries the genetic variant.

In rare cases when both parents carry the gene, there is a 50% chance the child will have mild or moderate VWD and a 25% chance they will have severe VWD.

Type 2N and 3

In these types of VWD, both parents must have a genetic variant that causes the condition for their children to develop it.

There is a 25% chance a child will get two copies of the variant, resulting in VWD, and a 50% chance they will get only one copy. In this case, the child will not have VWD themselves, but they will be able to pass on the gene to their children.

When only one parent has type 2N or 3, their children will definitely receive one copy of a gene for VWD but will not develop the condition.

If a person has symptoms of VWD, doctors may recommend a range of tests. Many are not genetic tests but instead blood tests that check for clotting factors in the blood.

People usually need to undergo the following blood tests to confirm a VWD diagnosis:

• VWF antigen
• VWF multimers to observe the structure of VWF proteins
• factor VIII clotting activity
• platelet aggregation tests to check how well platelets work
• ristocetin cofactor to check how well VWF works

Doctors may repeat blood tests several times to ensure an accurate diagnosis. This is because the levels of clotting proteins in the blood can vary due to several factors, such as infections, pregnancy, and stress, and these variations can affect the test results.

Alternatively, doctors may perform genetic testing. This could be in addition to the blood tests or instead of those tests. If a person does have a gene for VWD, the doctor may recommend testing other family members too.

A genetic counselor can explain what VWD genes do, a person’s risk of symptoms or complications, and the chances that a person may pass those genes onto any children they have.

Here are some common questions about VWD.

Can you have VWD if your parents do not?

Yes, a person can have VWD even if their parents do not. In the autosomal recessive inheritance pattern, both parents can carry a VWD gene variant. If they both pass down this variant to their child, the child can have VWD, even if the parents do not have symptoms.

Rarely, people can develop spontaneous changes in their genes that cause VWD, even when they have no family history. A person could then pass down the genetic variant to any children they have. It is also possible for some medical conditions to destroy VWF, causing VWD that is not genetic.

Does VWD affect life expectancy?

VWD does not usually affect life expectancy. In fact, mild VWD may have some benefits. Because it causes platelets not to form clots as easily, people with VWD may have a lower risk of heart attack and stroke.

Can you outgrow VWD?

It may be possible to outgrow VWD. This is because the levels of VWF increase with age, which may improve the blood’s ability to clot.

VWD is a bleeding disorder that people usually inherit from their parents due to a genetic variation.

The inheritance pattern for VWD can be dominant or recessive, depending on the type. However, the most common pattern is autosomal dominant, meaning only one parent needs to have a VWD gene for their child to develop the condition.

There are several types of VWD, but type 1 is the most prevalent. A doctor may confirm a VWD diagnosis with blood tests, genetic tests, or a combination of the two.