Type 2N von Willebrand disease: Is it always a recessive trait?

Abstract

Type 2N is a relatively rare form of von Willebrand disease (VWD), with a frequency calculated in <5% of all VWD cases, representing 6–22.5% of type 2 VWD. In our institution, its frequency was calculated in 0.56% of total VWD patients, and in 3.3% of type 2 VWD. It is described as a recessive disease due to disease-causing variants (DCV) located within the FVIII binding site of the von Willebrand factor (VWF) involving the first 272 amino acids of the D′ -D3 domains encoded by exons 18–23. However, to discard the presence of DCV outside of FVIII binding regions associated with impaired FVIII binding, exons 17 to 27 of the VWF gene should be sequenced. Heterozygotes are considered carriers of the defect and mostly asymptomatic, but homozygotes and compound heterozygotes have clinical manifestations and laboratory phenotype which are frequently mistaken for those of mild hemophilia A.