Genetic studies by NGS Panel 
Panel for Congenital Erythrocytosis / Familial Polycythemia (Code 10050)

Familial polycythemia or congenital erythrocytosis is an inherited hematological disorder, characterized by a high absolute mass of red blood cells caused by an uncontrolled production of red blood cells. The prevalence is unknown. Hematologic disorder is present from birth, but clinical symptoms, if developed, can be discovered at any time during childhood or adulthood. Clinical symptoms include headache, dizziness, epistaxis, and exertional dyspnea.


Neither primary familial polycythemia nor secondary polycythemia has a propensity for leukemic transformation or the development of other myeloproliferative neoplasms, but they are associated with a high risk of thrombosis and vascular mortality in adulthood (Cario, 2005).


Hematologic manifestations include the presence of isolated erythrocytosis without progression to leukemia or other myeloproliferative disorders, absence of splenomegaly, normal white blood cell and platelet counts, and low levels of serum EPO (in primary familial polycythemia) or normal or high EPO (in secondary family polycythemias).


The differential diagnosis includes polycythemia vera which can be excluded based on the absence of mutations in the JAK2 gene (9p24).


Familial polycythemia is caused by mutations in different genes:

Primary familial polycythemia or type 1 familial erythrocytosis is due to mutations in the EPO receptor gene (EPOR, 19p13.3-p13.2). EPOR mutations lead to a hypersensitivity to EPO and cause the receptor to be constantly activated to stimulate the production of red blood cells from erythroid progenitor cells, preventing a deactivation mechanism. Inheritance is usually autosomal dominant although sporadic cases have been reported. At least 14 mutations have been described in single families. The diagnosis is based on the evidence of finding relatives with isolated erythrocytosis without splenomegaly, low levels of serum EPO, normal affinity of hemoglobin for oxygen, and erythroid progenitors in the bone marrow exhibiting a hypersensitivity to EPO.


Polycythemia associated with von Hippel-Lindau syndrome or Chuvash polycythemia or type 2 familial erythrocytosis is due to mutations in the VHL gene (3p25). It is an autosomal recessive disorder characterized by increased red blood cell mass, increased serum erythropoietin (EPO) levels, and normal oxygen affinity. Familial erythrocytosis-2 has characteristics of both primary and secondary erythrocytosis (Prchal, 2005).



Type 3 familial erythrocytosis is an autosomal dominant disorder due to mutations in the EGLN1 gene (1q42). EPO levels in these patients are inappropriately normal (Ladroue et al., 2008).


Type 4 familial erythrocytosis is an autosomal dominant disorder characterized by increased serum red blood cell mass and elevated serum hemoglobin and erythropoietin (EPO). It is due to mutations in the EPAS1 gene (2p21) that encodes the protein HIF2A (Percy et al., 2008).



  • Cario, H. Childhood polycythemias/erythrocytoses: classification, diagnosis, clinical presentation, and treatment. Ann. Hematol. 84: 137-145, 2005. [PubMed: 15599750]
  • de la Chapelle, A., Sistonen, P., Lehvaslaiho, H., Ikkala, E., Juvonen, E. Familial erythrocytosis genetically linked to erythropoietin receptor gene. Lancet 341: 82-84, 1993. [PubMed: 8093406]
  • Ladroue, C., Carcenac, R., Leporrier, M., Gad, S., Le Hello, C., Galateau-Salle, F., Feunteun, J., Pouyssegur, J., Richard, S., Gardie, B. PHD2 mutation and congenital erythrocytosis with paraganglioma. New. Eng. J. Med. 359: 2685-2692, 2008. [PubMed: 19092153]
  • Pastore, Y., Jedlickova, K., Guan, Y., Liu, E., Fahner, J., Hasle, H., Prchal, J. F., Prchal, J. T. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. Am. J. Hum. Genet. 73: 412-419, 2003. Note: Erratum: Am. J. Hum. Genet. 74: 598 only, 2004. [PubMed: 12844285]
  • Percy, M. J., Furlow, P. W., Beer, P. A., Lappin, T. R. J., McMullin, M. F., Lee, F. S. A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove. Blood 110: 2193-2196, 2007. [PubMed: 17579185]
  • Percy, M. J., Furlow, P. W., Lucas, G. S., Li, X., Lappin, T. R. J., McMullin, M. F., Lee, F. S. A gain-of-function mutation in the HIF2A gene in familial erythrocytosis. New Eng. J. Med. 358: 162-168, 2008. [PubMed: 18184961]
  • Prchal, J. T. Polycythemia vera and other primary polycythemias. Curr. Opin. Hemat. 12: 112-116, 2005. [PubMed: 15725900]