From the Guidelines
Von Willebrand disease is inherited in an autosomal dominant pattern for most types, with a 50% chance of passing the condition to each child, while Type 3 follows an autosomal recessive pattern, requiring two copies of the altered gene. The inheritance pattern of Von Willebrand disease is complex, with different types having different modes of inheritance. According to the 2008 NHLBI/NIH guidelines, as reported in the American Journal of Hematology in 2009 1, the disease is primarily classified into three main types: Type 1, Type 2, and Type 3.
Key Characteristics of Each Type
- Type 1: partial quantitative deficiency, accounting for ~75% of symptomatic persons
- Type 2: qualitative deficiency, with four subtypes (2A, 2B, 2M, 2N), and Type 2A being more common than the others
- Type 3: virtually complete quantitative deficiency, affecting only ~1 person in 1,000 The VWF gene, responsible for producing von Willebrand factor, is located on chromosome 12, and mutations in this gene lead to reduced or dysfunctional von Willebrand factor, resulting in bleeding tendencies, as noted in the study 1.
Implications for Inheritance
Given the autosomal dominant pattern for Type 1 and Type 2, and the autosomal recessive pattern for Type 3, genetic testing can identify specific mutations and help determine inheritance patterns in families, which is crucial for genetic counseling and understanding transmission risks and management options, as implied by the study 1.
Genetic Counseling
Genetic counseling is recommended for affected individuals planning to have children to understand the risks and management options associated with Von Willebrand disease, considering the significant impact on morbidity, mortality, and quality of life.
From the Research
Inheritance of Von Willebrand Disease
- Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by deficiencies in von Willebrand factor (VWF) 2, 3, 4.
- The disease is autosomally inherited, meaning it can be inherited from either parent, and affects both males and females equally 3, 4.
- There are three main types of VWD: type 1, type 2, and type 3, each with different levels of VWF deficiency and clinical symptoms 3, 4, 5.
Diagnosis and Classification
- Diagnosis of VWD is based on a combination of clinical assessment, laboratory tests, and family history 2, 3.
- Laboratory tests include measurements of VWF levels and activity, as well as assays to assess VWF function 2, 3, 4.
- The current classification of VWD includes types 1, 2A, 2B, 2M, 2N, and 3, each with distinct clinical and laboratory characteristics 3, 4.
Genetic Aspects
- Most VWD patients have an identifiable VWF gene DNA variant, which can inform diagnosis, treatment, and family counseling 2.
- Molecular genetic testing can provide additional diagnostic information, particularly for type 2 and 3 VWD 4.
- Next-generation sequencing is being increasingly used to provide comprehensive VWF sequence information for patients with known or suspected VWD 2.
Treatment and Management
- Treatment of VWD typically involves the use of desmopressin and plasma-derived VWF concentrates, as well as adjunctive agents such as antifibrinolytics 2, 5.
- The choice of treatment depends on the type and severity of VWD, as well as the individual patient's response to treatment 5, 6.
- Recent studies have quantified the relationship between desmopressin concentration and VWF activity in type 1 VWD patients, informing optimal dosing regimens 6.