title: Familial chronic myeloproliferative disorders: the state of the art.
abstract: Familial chronic myeloproliferative disorders are defined when in the same pedigree at least two relatives have a chronic myeloproliferative disorder (CMD) as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). This condition should be distinguished from inherited disorders with Mendelian transmission and single haematopoietic lineage proliferation, named hereditary erythrocytosis and thrombocytosis. The recently discovered mutations in patients with CMD (V617F and exon 12 of JAK2 gene, MPL gene), and those identified in hereditary erythrocytosis and in hereditary thrombocytosis have improved our ability to discriminate these conditions. In familial CMD, the JAK2 mutations are acquired and occur as secondary genetic events. As both mutations of the JAK2 gene have been reported in the same pedigree, a genetic predisposition to the acquisition of the JAK2 mutations is supposed to be inherited. The prevalence of familial cases within CMD is at least 7.6%. The inheritance pattern of familial CMD is consistent with an autosomal dominant trait with decreased penetrance. The clinical presentation at diagnosis of patients with familial CMD does not differ from that of patients with sporadic CMD. In addition, patients with familial CMD develop the same type of complications (thrombosis and haemorrhage) and disease evolution (post-PV myelofibrosis, post-ET myelofibrosis and leukaemia) observed in patients with sporadic CMD. The 10-year survival is 83% for patients with familial PV, 100% for those with familial ET, and 30% for those with familial PMF. The aim of this review is to focus the state of the art of familial CMD and to offer an overview of inherited conditions causing erythrocytosis and thrombocytosis.
authors.affiliation: Department of Hematology, University of Pavia Medical School, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. elisarumi@hotmail.com
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
mesh_terms: D002908:Chronic Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D009154:Mutation; D011086:Polycythemia / Q000235:genetics; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics*; D013922:Thrombocytosis / Q000235:genetics
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2