What are the chances that the children of a father who is homozygous for Factor V Leiden (FVL) will inherit the mutation?

Inheritance Risk of Factor V Leiden from Homozygous Father

If a father is homozygous for Factor V Leiden, all of his children will inherit at least one copy of the mutation (100% chance of being heterozygous carriers). 1

Genetic Inheritance Pattern of Factor V Leiden

Factor V Leiden (FVL) follows an autosomal dominant inheritance pattern, meaning:

• A homozygous father has two copies of the FVL mutation
• He will pass one of these copies to each child
• The mother's Factor V status determines if children will be heterozygous or homozygous:
  • If mother has no FVL mutation: All children will be heterozygous (one copy)
  • If mother is heterozygous: 50% chance children will be homozygous, 50% chance heterozygous
  • If mother is homozygous: All children will be homozygous

Clinical Significance for Children Who Inherit FVL

The clinical implications for children who inherit FVL vary based on zygosity and other factors:

Heterozygous FVL Carriers:

• Approximately 3.5-fold increased risk of initial venous thromboembolism (VTE) compared to non-carriers 1
• Annual VTE risk of approximately 35 per 10,000 (compared to baseline of 10 per 10,000) 1
• Generally not recommended for prophylactic anticoagulation in the absence of other risk factors 2

Homozygous FVL Carriers:

• Approximately 18-fold increased risk of initial VTE compared to non-carriers 1
• Annual VTE risk of approximately 180 per 10,000 1
• May warrant consideration of preventive measures due to significantly higher thrombotic risk 1

Important Considerations for Management

Risk Modifiers

• The presence of additional thrombophilic mutations significantly increases risk 3, 4
• Circumstantial risk factors (surgery, pregnancy, oral contraceptives) further increase risk 1, 2
• Age may influence the relative risk of VTE in FVL carriers 1

Testing and Management

• Testing for FVL in asymptomatic family members should be decided individually 2
• For heterozygous carriers without prior thrombosis, long-term anticoagulation is not routinely recommended 2
• For homozygous carriers, the risk is "sufficiently high to consider preemptive anticoagulation therapy" although no formal studies have assessed this approach 1

Special Circumstances

• Female carriers should be counseled about increased risks during pregnancy and with oral contraceptive use 1, 2
• Prophylactic anticoagulation may be considered in high-risk clinical settings even for asymptomatic carriers 2

Common Pitfalls in Management

1. Overestimating risk in heterozygous carriers - the absolute risk remains relatively low despite the increased relative risk
2. Failing to consider additional risk factors that may compound thrombotic risk
3. Unnecessary long-term anticoagulation in asymptomatic heterozygous carriers, where bleeding risk may outweigh benefits
4. Not recognizing that homozygous carriers have substantially higher risk than heterozygous carriers

Remember that while FVL increases thrombotic risk, many carriers never experience thrombotic events, and management decisions should carefully weigh thrombosis risk against bleeding risk from anticoagulation.