What is the chance of offspring inheriting alpha thalassemia trait from a mother with alpha thalassemia trait and a father without the trait?

Alpha Thalassemia Inheritance Risk

When a mother has alpha thalassemia trait and the father has no trait, each offspring has a 50% chance of inheriting the alpha thalassemia trait and a 50% chance of being completely unaffected—there is no risk of severe disease.

Genetic Inheritance Pattern

Alpha thalassemia trait typically involves deletion of one or two alpha-globin genes (out of four total). The inheritance follows autosomal recessive patterns 1, 2:

• If the mother is a silent carrier (one gene deletion: -α/αα), each child has:

  • 50% chance of inheriting the deletion (becoming a silent carrier)
  • 50% chance of inheriting normal genes (no trait)
  • 0% risk of clinically significant disease 3

• If the mother has alpha thalassemia trait (two gene deletions: --/αα or -α/-α), each child has:

  • 50% chance of inheriting one deleted chromosome (becoming a carrier with one or two gene deletions)
  • 50% chance of inheriting the normal chromosome (no trait or silent carrier)
  • 0% risk of Hemoglobin H disease or Bart's hydrops fetalis 1, 4

Why Severe Disease Cannot Occur

The critical point is that the father contributes two normal alpha genes on each chromosome, which prevents any severe forms of alpha thalassemia 3:

• Hemoglobin H disease requires three gene deletions (only possible if both parents are carriers) 4
• Hemoglobin Bart's hydrops fetalis requires four gene deletions (only possible if both parents have two-gene deletions) 5, 3
• Since the father has no trait, he can only contribute normal alpha genes 1

Clinical Implications for Offspring

Children who inherit the trait will be asymptomatic and require no treatment 2, 3:

• Silent carriers and those with alpha thalassemia trait have normal life expectancy 3
• They will have microcytic red blood cells (MCV <80 fL) with normal or elevated RBC count 6
• No monitoring or treatment is needed 2
• The only clinical significance is for their own future reproductive planning 1

Essential Counseling Points

Genetic counseling should emphasize that this couple faces no risk of having a child with severe alpha thalassemia 6:

• Partner testing confirmed the father is not a carrier, which is reassuring 6
• Future pregnancies carry the same 50/50 risk pattern with no severe disease risk 1
• Children who inherit the trait should receive genetic counseling before their own reproductive planning 1, 5
• Cascade testing of other family members on the maternal side may be appropriate 5

Common Pitfall to Avoid

Do not confuse this scenario with situations where both parents are carriers—that is when severe disease becomes possible 6, 3:

• The 25% risk of severe disease only applies when both parents carry alpha thalassemia mutations 6
• In this case, with only one parent affected, the maximum number of gene deletions possible in offspring is two (trait), not three or four (severe disease) 4