A 40-year-old woman of Mediterranean descent with beta-thalassaemia trait (HbA2 5.8%, mild microcytosis, Hb 11.2 g/dL) is referred for counselling. Her husband also has beta-thalassaemia trait confirmed on HPLC. What is the risk that their child will have beta-thalassaemia major, and what prenatal diagnosis option is available at 11–14 weeks of gestation?

• A 50% risk of beta-thalassaemia major; amniocentesis at 16–18 weeks is the only option
• B 100% risk; the couple should consider adoption
• C 25% risk; preimplantation genetic testing (PGT) is only option before 14 weeks
• D 25% risk of beta-thalassaemia major; chorionic villus sampling (CVS) for DNA analysis is available at 11–14 weeks ✓

Explanation

When both parents carry beta-thalassaemia trait (heterozygous), each pregnancy carries a 25% probability of beta-thalassaemia major (homozygous), 50% trait carrier, and 25% normal. Chorionic villus sampling (CVS) performed at 11–14 weeks gestation provides fetal DNA for mutation analysis by PCR/sequencing, allowing first-trimester diagnosis. Amniocentesis is available at 16–18 weeks as an alternative. Preimplantation genetic testing is available via IVF before conception but not a prenatal option.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.