Preferred Label : Von willebrand disease, type 1;
Symbol : VWD1;
CISMeF acronym : VWD1;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Vwd, type 1; Von willebrand disease, type I;
Description : Von Willebrand disease is the most common inherited bleeding disorder. It is characterized
clinically by mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged
bleeding after surgery or trauma. The disorder results from a defect in platelet aggregation
due to defects in the von Willebrand factor protein. Von Willebrand factor is a large,
multimeric protein that plays a role in platelet adhesion and also serves as a carrier
for the thrombotic protein factor VIII (F8; 300841). F8 is mutated in hemophilia A
(review by Goodeve, 2010). - Classification of von Willebrand Disease The classification
of von Willebrand disease has a long and complex history. The current classification
is based on that described by Sadler (1994) and updated by Sadler et al. (2006), which
delineates 3 main subtypes according to the mutant protein phenotype. An earlier classification
developed by a working party of the European Thrombosis Research Organization was
provided by Zimmerman and Ruggeri (1983). Von Willebrand Disease Type 1 VWD type 1
is a quantitative partial deficiency of circulating VWF. In this type of VWD, there
is a normal ratio of functional VWF activity (VWF:RCo, ristocetin cofactor activity)
relative to VWF antigen level (VWF:Ag) (Sadler et al., 2006, Goodeve, 2010). Mannucci
(2004) stated that type 1 VWD accounts for 60 to 80% of all VWD cases and is characterized
by mild to moderate quantitative deficiencies of VWF and factor VIII, which are coordinately
reduced to 5 to 30% of normal plasma levels (pathogenic levels of 5 to 30 IU/dL).
In an updated consensus statement, Sadler et al. (2006) noted that (1) some cases
of VWF type 1 may have subtle abnormal VWF multimer patterns, but still retain normal
functional activity, and (2) that loci other than VWF may be responsible for some
cases of VWD. In reviews, James and Lillicrap (2008) and Lillicrap (2009) stated that
the knowledge of the pathogenesis and molecular basis of type 1 VWD is still in its
infancy and still evolving. Population studies have indicated that type 1 VWD is a
complex genetic trait associated with a variety of genetic and environmental factors,
and that additional loci in addition to VWF are likely involved. There is still uncertainty
about the pathogenicity of many identified putative VWF variants, and the incomplete
penetrance and variable expressivity of type 1 disease contributes to complexity in
diagnosis and understanding of disease pathogenesis. Von Willebrand Disease Type 2
VWD type 2 (613554), which accounts for 10 to 30% of cases, is characterized by qualitative
abnormalities of VWF; it is further divided into subtypes 2A, 2B, 2M, and 2N. The
mutant VWF protein in types 2A, 2B, and 2M are defective in their platelet-dependent
function, whereas the mutant protein in type 2N is defective in its ability to bind
F8 (Mannucci, 2004; Sadler et al., 2006; Goodeve, 2010). Von Willebrand Disease Type
3 VWD type 3 (277480), which accounts for 1 to 5% of cases, is characterized by a
severe quantitative defect of VWF in plasma (less than 1% of normal plasma levels),
with low but usually detectable levels of factor VIII (1 to 10% of normal plasma levels).
In the rare type 3 disease (1 in 1 million people), symptoms are more frequent and
severe (Mannucci, 2004, Sadler et al., 2006).;
Inheritance : Autosomal dominant;
Molecular basis : Caused by mutation in the von Willebrand factor gene (VWF, 613160.0028);
Laboratory abnormalities : Decreased levels of plasma VWF antigen; Decreased levels of plasma factor VIII;
Prefixed ID : #193400;
Origin ID : 193400;
UMLS CUI : C1264039;
Automatic exact mappings (from CISMeF team)
- Broader ORDO disease(s)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- Not associated HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
