Is polycythemia vera (a blood disorder characterized by excessive red blood cell production) hereditary?

Is Polycythemia Vera Hereditary?

Polycythemia vera (PV) is generally not considered a hereditary condition but rather an acquired myeloproliferative neoplasm characterized by a somatic JAK2 mutation in more than 95% of cases. 1, 2, 3

Genetic Basis of Polycythemia Vera

• PV is characterized by the presence of the JAK2V617F mutation in exon 14 of JAK2 in over 95% of patients 2
• This mutation is acquired (somatic) rather than inherited in the germline
• The mutation leads to constitutive activation of the JAK-STAT pathway, resulting in excessive production of red blood cells

Rare Familial Cases

While PV is predominantly a non-hereditary condition, there are rare documented cases of familial occurrence:

• The literature contains only a few authentic reports of familial PV 4
• A 1976 study described PV occurring in 3 sisters within a family of 8 females 4
• These cases are extremely uncommon and represent exceptions rather than the rule

Distinguishing PV from Hereditary Polycythemias

It's important to differentiate PV from truly hereditary forms of polycythemia:

• Chuvash polycythemia is a congenital, hereditary form of polycythemia that is endemic in Russia 5

  • Associated with mutations in the von Hippel-Lindau gene on chromosome 3 5
  • Results in abnormal oxygen homeostasis

• Some cases of autosomal-dominant congenital polycythemia carry activating mutations of the erythropoietin receptor (EPOR) gene 5

  • These mutations result in a C-terminal-truncated receptor that enhances signal transduction
  • Serum EPO levels are usually low in such patients

Diagnostic Approach to Differentiate Types of Polycythemia

When evaluating a patient with elevated hemoglobin/hematocrit:

1. Test for JAK2 V617F mutation - present in >95% of PV cases 1, 2
2. Measure serum erythropoietin level - typically low in PV, elevated or normal in secondary polycythemia 1
3. Consider bone marrow biopsy - shows hypercellularity with trilineage growth in PV 1
4. Evaluate for secondary causes of polycythemia (smoking, sleep apnea, etc.) 3
5. Consider genetic testing for hereditary polycythemia if JAK2 mutation is absent and family history suggests hereditary pattern

Clinical Implications

The non-hereditary nature of PV has important implications:

• No need for genetic screening of family members of PV patients
• Treatment focuses on the individual patient rather than family-based interventions
• Management includes phlebotomy to maintain hematocrit <45%, low-dose aspirin, and cytoreductive therapy for high-risk patients 1, 3

Common Pitfalls

• Mistaking PV for hereditary polycythemia or vice versa
• Overlooking rare familial cases of PV
• Failing to test for JAK2 mutations to confirm PV diagnosis
• Not considering secondary causes of polycythemia when JAK2 mutation is absent 1

In summary, while rare familial clusters of PV have been reported, the disease is predominantly an acquired myeloproliferative neoplasm characterized by somatic JAK2 mutations rather than a hereditary condition passed through generations.