Although PV is usually sporadic, reports of familial clustering have been documented. Studies have described multiple cases of PV or other MPNs within the same family, suggesting inherited factors that increase susceptibility to developing somatic mutations [2][6].

This does not mean PV itself is inherited. Instead:

• A shared genetic background may increase the likelihood of specific mutations.
• Environmental exposures (e.g., air pollution, secondhand smoke) could interact with predisposition.
• Families with clustering still show variability; one sibling may develop PV, another essential thrombocythemia (too many platelets), or none at all.

Thus, while family history is notable, most individuals with PV do not have relatives with the disease. Most people with PV are the only ones in their family [1].

It is crucial to separate PV from hereditary polycythemia or erythrocytosis syndromes.

PV (acquired MPN):

• Somatic JAK2 mutations.
• Risk of progression to myelofibrosis or acute leukemia (fast-growing blood cancer).
• Treated with phlebotomy, aspirin, and cytoreduction (medications to lower blood cell counts, such as hydroxyurea, interferon).

Hereditary polycythemia (rare):

• Germline mutations in genes like EPOR, VHL, EGLN1, or hemoglobin variants [7].
• Presents earlier in life, sometimes in childhood.
• Typically lacks features of MPNs (splenomegaly, leukocytosis, thrombocytosis).
• Managed differently, often with periodic phlebotomy but not cancer-directed treatments used for blood cancers.

These inherited conditions confirm that while polycythemia can be hereditary, polycythemia vera rarely is.

Cause-of-disease studies explored environmental and hereditary theories. Over time, molecular biology clarified that clonal stem-cell mutations underpin PV [4][8].

Current understanding:

• JAK2 mutation testing confirms the diagnosis.
• Family history is noted but usually not the deciding factor.
• Risk stratification relies more on age and thrombotic history than heredity [5][6].

Thus, modern PV is framed as a somatic mutation–driven malignancy, with hereditary cases being exceptional.

• Diagnosis: JAK2 mutation testing is central. Hereditary polycythemia is suspected when high red blood cell levels occur at a young age with a negative JAK2 status.
• Treatment decisions: Therapy depends on thrombotic risk, not inheritance.
• Counseling: Patients often ask if children are at risk. The answer is that risk is not directly inherited, although a rare familial predisposition may exist.

This reassures most patients that PV is not a straightforward hereditary disease. [9]

1. Is PV hereditary?

No, PV is generally not hereditary. It usually results from acquired JAK2 mutations in bone marrow stem cells. Rarely, PV occurs in families, but this is more likely a reflection of genetic predisposition rather than direct inheritance.

2. Can children of someone with PV develop it?

The vast majority will not. PV is usually sporadic, and children are not considered at high risk. Familial clustering is rare and does not necessarily imply that inheritance is guaranteed.

3. What’s the difference between hereditary polycythemia and PV?

Hereditary polycythemia stems from inherited germline mutations (like EPOR or VHL) and often begins in childhood. PV is usually an acquired neoplasm (condition that develops during life) with JAK2 mutations, more common in adults, and carries risks of clotting and progression.

4. Should family members be screened if someone has PV?

Routine screening is not recommended. Unless symptoms or abnormal blood counts appear in relatives, genetic testing is unnecessary.

5. Does knowing about genetics change PV treatment?

Yes, but indirectly. JAK2 mutation testing confirms PV, guiding therapy. In hereditary erythrocytosis, treatment is supportive, not cancer-directed. In PV, therapy aims to prevent clots and manage symptoms.

1. Spivak, J. L. (2018). Polycythemia vera. Current Treatment Options in Oncology, 19(2), 12.
2. Tefferi, A., & Spivak, J. L. (2005). Polycythemia vera: scientific advances and current practice. Semin Hematol, 42(4), 206–220.
3. Tremblay, D., Kremyanskaya, M., Mascarenhas, J., & Hoffman, R. (2024). Diagnosis and treatment of polycythemia vera: a review. JAMA.
4. Fernandez-Luna, J. L., et al. (1998). Pathogenesis of polycythemia vera. Haematologica, 83(2), 150–158.
5. Passamonti, F. (2012). How to manage polycythemia vera. Leukemia, 26(5), 870–874.
6. Tefferi, A., & Barbui, T. (2020). Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk‐stratification and management. American journal of hematology, 95(12), 1599-1613.
7. Kralovics, R., & Prchal, J. T. (2000). Congenital and inherited polycythemia. Curr Opin Pediatr, 12(1), 29–34.
8. Michiels, J. J., et al. (2013). Physiopathology, etiologic factors, diagnosis, and course of polycythemia vera as related to therapy according to William Dameshek, 1940–1950. Turk J Hematol, 30(2), 102.
9. Schafer, A. I. (2006). Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood, 107(11), 4214–4222.