Differential Diagnosis for Heavy Family History of Second Trimester Pregnancy Loss and Stroke in the Young

Given a negative work-up for antiphospholipid syndrome, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Factor V Leiden thrombophilia: This is a common inherited disorder that increases the risk of thrombosis. It could explain both the second trimester pregnancy losses (due to placental insufficiency from thrombosis) and the strokes in young family members (due to venous or arterial thrombosis). The presence of a significant family history of these events without another clear cause makes this a plausible diagnosis.

• Other Likely Diagnoses

  • Prothrombin G20210A mutation: Similar to Factor V Leiden, this is another inherited thrombophilic condition that could lead to an increased risk of pregnancy loss and stroke in young individuals.
  • Protein S or Protein C deficiency: These are also inherited thrombophilias that could explain the family history of thrombotic events, including pregnancy losses and strokes.
  • Hyperhomocysteinemia: Elevated levels of homocysteine can increase the risk of thrombosis, which might explain the family history of strokes and pregnancy losses. This condition can be inherited or acquired.

• Do Not Miss Diagnoses

  • Sickle Cell Disease or Sickle Cell Trait: While less common, sickle cell disease or trait can increase the risk of stroke and pregnancy complications, including second trimester losses. Missing this diagnosis could have significant implications for family members.
  • Moyamoya Disease: A rare condition that affects the blood vessels in the brain, leading to a higher risk of stroke. It's crucial not to miss this diagnosis due to its severe implications and the availability of specific treatments.
  • Fabry Disease: An inherited disorder that can lead to stroke and other systemic complications. Early diagnosis is critical for the initiation of potentially disease-modifying treatments.

• Rare Diagnoses

  • Ehlers-Danlos Syndrome (vascular type): This condition affects the blood vessels and can lead to an increased risk of stroke and other vascular events. While rare, it's an important consideration in families with a history of unexplained vascular events.
  • Pseudoxanthoma Elasticum (PXE): A genetic disorder that can lead to mineralization and fragmentation of elastic fibers in some tissues, including blood vessels, potentially increasing the risk of stroke and other vascular complications.
  • Homocystinuria: A genetic disorder that affects the metabolism of the amino acid methionine and homocysteine, leading to elevated homocysteine levels and an increased risk of thrombosis and stroke.