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Inherited\/congenital erythrocytosis (CE) of both primary and secondary types is increasingly recognized as the cause in many patients in whom acquired, especially neoplastic causes have been excluded. During the past two decades, the underlying molecular mechanisms of CE are increasingly getting unraveled. Gain\u2010in\u2010function mutations in the erythropoietin receptor gene were among the first to be characterized in a disorder termed primary familial and congenital polycythemia. Another set of mutations affect the components of the oxygen\u2010sensing pathway. Under normoxic conditions, the hypoxia\u2010inducible factor (HIF), upon hydroxylation by the prolyl\u20104\u2010hydroxylase domain protein 2 (PHD2) enzyme, is degraded by the von Hippel\u2010Lindau protein. In hypoxic conditions, failure of prolyl hydroxylation leads to stabilization of HIF and activation of the <jats:italic>EPO<\/jats:italic> gene. CE has been found to be caused by loss\u2010of\u2010function mutations in <jats:italic>VHL<\/jats:italic> and <jats:italic>PHD2<\/jats:italic>\/<jats:italic>EGLN1<\/jats:italic> as well as gain\u2010of\u2010function mutations in <jats:italic>HIF\u20102\u03b1<\/jats:italic> (<jats:italic>EPAS1<\/jats:italic>), all resulting in constitutive activation of EPO signaling. Apart from these, globin gene mutations leading to formation of high oxygen affinity hemoglobins also cause CE. Rarely, bisphosphoglycerate mutate mutations, affecting the 2,3\u2010bisphosphoglycerate levels, can increase the oxygen affinity of hemoglobin and cause CE. This narrative review examines the current mutational spectrum of CE and the distinctive pathogenetic mechanisms that give rise to this increasingly recognized condition in various parts of the world.<\/jats:p>","DOI":"10.1111\/ejh.13632","type":"journal-article","created":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T10:50:20Z","timestamp":1618138220000},"page":"29-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Congenital erythrocytosis"],"prefix":"10.1111","volume":"107","author":[{"given":"Nabhajit","family":"Mallik","sequence":"first","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education &amp; Research Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-5423","authenticated-orcid":false,"given":"Reena","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Hematology 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