Genetic carrier screening — structured SAQ (15 marks)

(a) Definition and the three-gene panel (3 marks)

One mark for the definition, one for naming all three genes, one for the universal-offer rationale.

• Definition: reproductive carrier screening is the testing of healthy individuals to identify carriers of autosomal recessive or X-linked conditions before or early in pregnancy, so couples can make informed reproductive choices.^[1]
• The three genes: cystic fibrosis, spinal muscular atrophy and fragile X syndrome.^[1]
• Offer to everyone planning or in early pregnancy, regardless of family history, because most affected children are born to couples with no family history.^[1]

(b) Inheritance and per-pregnancy risk (3 marks)

One mark for AR mechanism, one for the one-in-four figure, one for carrier-vs-affected distinction. ^[1]

• Autosomal recessive: both parents must be carriers for the child to be at risk; carriers are themselves unaffected.^[1]
• Per pregnancy: one in four chance of an affected child, one in two chance of a carrier, one in four chance of neither.^[1]
• Contrast with X-linked (fragile X): the woman carries; sons at risk of the full mutation; premutation can expand across generations.^[1][9]

(c) Pre-test counselling and timing (4 marks)

One mark for timing, one for the timing rationale, one for residual risk, one for non-directive framing. ^[1]

• Timing: ideally before conception, so all options remain open; if already pregnant, first trimester.^[1]
• Rationale: preconception a result allows IVF with PGT, donor gametes, or choosing not to conceive; in pregnancy options narrow to prenatal diagnosis and possible termination.^[1][5]
• Residual risk: a negative screen reduces but does not eliminate risk — never say 'zero risk'.^[1][6]
• Non-directive: explain what positive, negative and variant-of-uncertain-significance results would mean; support any reproductive choice.^[1]

(d) Reproductive options after a both-partner positive result (5 marks)

One mark per option, max five.

• Accept the risk — conceive naturally with or without postnatal testing.^[1]
• Natural conception with prenatal diagnosis (CVS or amniocentesis) and the option of termination of an affected pregnancy.^[1]
• IVF with pre-implantation genetic testing (PGT) — select unaffected embryos.^[5]
• Donor gametes (sperm, eggs or embryos) from a non-carrier.^[1]
• Adoption, or choosing not to have children.^[1]
• State referral to clinical genetics for counselling on SMA severity, prognosis and support.^[1]
• Evidence it changes decisions: in Mackenzie's Mission, 76.6% of newly at-risk couples had used or planned a reproductive intervention within 3 months, with low decisional regret.^[2]
• Fragile X positive: counsel FXPOI risk and family cascade in addition to reproductive risk.^[9]