Phenotypic Heterogeneity in Patients with Homozygous Prothrombin 20210AA Genotype : A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology

Venous thromboembolic events (VTEs) affect an estimated 1 in 1000 people annually, resulting in ∼50,000 deaths, with prevalence increasing with age. The genetic contributors to thrombosis have been described and further explored within the last 15 years as molecular diagnostic techniques have become more widely used. The prothrombin G20210A mutation is the second most common inherited thrombotic risk factor after factor V Leiden. Generally present in less than 5% of the population, the mutation's prevalence varies greatly with ethnicity. The G20210A mutation confers a mildly increased thrombotic risk that is compounded by the presence of other risk factors. One striking characteristic of the G20210A mutation is the phenotypic heterogeneity of the rare homozygous cases. Forty percent of the reported homozygous cases are asymptomatic. Many of the symptomatic patients have additional risk factors that might compound the thrombotic risk. We present here a review of the literature for the homozygous prothrombin G20210A mutation and describe additional cases that exemplify the heterogeneous nature of this entity.