Type 2 von Willebrand Disease is Autosomal Dominant
Type 2 von Willebrand disease (VWD) is inherited in an autosomal dominant pattern. 1, 2
Inheritance Patterns in von Willebrand Disease
Von Willebrand disease is the most common inherited bleeding disorder, affecting approximately 1% of the general population. The inheritance pattern varies by VWD type:
- Type 1 VWD: Autosomal dominant (partial quantitative deficiency)
- Type 2 VWD: Autosomal dominant (qualitative deficiency)
- Includes subtypes 2A, 2B, 2M, and 2N
- Type 3 VWD: Autosomal recessive (virtually complete quantitative deficiency) 3
Type 2 VWD Characteristics
Type 2 VWD represents a qualitative deficiency of von Willebrand factor (VWF), meaning the VWF protein is present but functions abnormally. It has four distinct subtypes:
- Type 2A: Most common subtype - characterized by decreased VWF-dependent platelet adhesion due to selective deficiency of high-molecular-weight VWF multimers
- Type 2B: Enhanced binding of VWF to platelet GPIb receptor, often associated with thrombocytopenia
- Type 2M: Decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight multimers
- Type 2N: Markedly decreased binding affinity for factor VIII 3, 4
Genetic Basis
The mutations causing Type 2 VWD are typically localized to specific regions of the VWF gene:
- Type 2 VWD mutations (2A, 2B, 2M, 2N) are primarily located in exons 18-28 of the VWF gene
- In contrast, mutations causing Types 1 and 3 are spread throughout the entire gene 1
Clinical Implications of Autosomal Dominant Inheritance
The autosomal dominant inheritance pattern of Type 2 VWD has important clinical implications:
- Each child of an affected individual has a 50% chance of inheriting the disorder
- Both males and females are affected equally, though women may be more symptomatic due to menstruation and childbirth
- Family history typically shows affected individuals in each generation
- A single copy of the mutated gene is sufficient to cause the disease 2, 5
Diagnostic Considerations
When evaluating a patient with suspected Type 2 VWD:
- Look for a family history consistent with autosomal dominant inheritance
- Assess for mucocutaneous bleeding symptoms (easy bruising, nosebleeds, gingival bleeding, heavy menstrual bleeding)
- Laboratory testing should include VWF antigen, ristocetin cofactor activity, and factor VIII levels
- Specific assays to determine VWD subtype are essential for proper classification and management 3, 5
Treatment Implications
Understanding the inheritance pattern helps with:
- Family screening and genetic counseling
- Predicting disease severity across generations
- Anticipating potential complications during surgery, trauma, or childbirth
- Planning appropriate treatment strategies based on subtype 4
Unlike Type 3 VWD (autosomal recessive), which may require prenatal diagnosis in at-risk pregnancies, Type 2 VWD rarely requires such intervention due to its generally milder clinical course and dominant inheritance pattern 5.