Polycythemia vera (PV), the most common form of primary polycythemia, is caused by somatic mutation in a single hematopoietic stem cell leading to clonal hematopoiesis. PV is a myeloproliferative disorder characterized predominantly by erythroid hyperplasia, but also by myeloid leukocytosis, thrombocytosis, and splenomegaly. Familial cases of PV are very rare and usually manifest in elderly patients (Cario, 2005). PV is distinct from the familial erythrocytoses (see, e.g., ECYT1, 133100), which are caused by inherited mutations resulting in hypersensitivity of erythroid progenitors to hormonal influences or increased levels of circulating hormones, namely erythropoietin (EPO; 133170) (Prchal, 2005).

Familial thrombocytosis in which the cause of the disease is a mutation in the MPL gene.

Thrombocytopenia-12 with or without myopathy (THC12) is an autosomal recessive disorder characterized by congenital thrombocytopenia apparent from infancy or early childhood. Most affected individuals have bleeding episodes, including petechiae, easy bruising, epistaxis, hematomas, menorrhagia, and increased bleeding after trauma or surgery, although rare patients may have thrombocytopenia without bleeding. Platelets are enlarged (macrothrombocytopenia), and there is an increase of circulating immature platelets, consistent with increased production. Patient platelets show hyposialylation due to GNE mutations, which causes increased removal of platelets from the circulation, shortened platelet lifespan, and resultant thrombocytopenia. In contrast to the thrombocytopenia, which is present since birth or early childhood, features of myopathy usually do not develop until the mid-twenties, similar to Nonaka myopathy (summary by Zhen et al., 2014, Izumi et al., 2014; Bottega et al., 2022). For a discussion of genetic heterogeneity of thrombocytopenia, see THC1 (313900).