The introduction of high throughput sequencing (HTS) techniques greatly improved the knowledge of inherited thrombocytopenias (ITs) over the last few years. A total of 33 different forms caused by molecular defects affecting at least 32 genes have been identified; along with the discovery of new disease-causing genes, pathogenetic mechanisms of thrombocytopenia have been better elucidated. Although the clinical picture of ITs is heterogeneous, bleeding has been long considered the major clinical problem for patients with IT. Conversely, the current scenario indicates that patients with some of the most common ITs are at risk of developing additional disorders more dangerous than thrombocytopenia itself during life. In particular, MYH9 mutations result in congenital macrothrombocytopenia and predispose to kidney failure, hearing loss, and cataracts, MPL and MECOM mutations cause congenital thrombocytopenia evolving into bone marrow failure, whereas thrombocytopenias caused by RUNX1, ANKRD26, and ETV6 mutations are characterized by predisposition to hematological malignancies. Making a definite diagnosis of these forms is crucial to provide patients with the most appropriate treatment, follow-up, and counseling. In this review, the ITs known to date are discussed, with specific attention focused on clinical presentations and diagnostic criteria for ITs predisposing to additional illnesses. The currently available therapeutic options for the different forms of IT are illustrated.
© 2016 by The American Society of Hematology. All rights reserved.