Prenatal diagnosis and reproductive genetics — branching viva

Station opening

Examiner: "The cell-free DNA screen is positive for trisomy 21 at high probability. The patient asks whether the baby has Down syndrome. What do you say?" [3]

Strong candidate (must-hit)

• A positive cfDNA screen is a screen, not a confirmed diagnosis. It raises probability and warrants counselling and an offer of diagnostic testing (CVS or amniocentesis by gestation). [3]
• Separates screening from diagnosis explicitly and states that confirmation is needed before any management decision. [3]
• Quotes contemporary, not legacy, procedure-related miscarriage risk for the diagnostic procedure. [4]

Weak candidate

• "Your baby has Down syndrome." [3]
• Offers a repeat cfDNA screen instead of diagnostic testing when pre-test probability is high. [3]

Branch A — Choosing the diagnostic test and the first-tier laboratory test

Examiner: "The patient consents to amniocentesis. What laboratory test do you request on the sample, and why?" [1]

Strong

• Requests chromosomal microarray as the first-tier test, because the anatomy scan shows a cardiac anomaly and microarray detects copy-number variants that karyotype misses. [1]
• Cites the Wapner trial: microarray identified clinically significant CNVs in approximately 6% of structurally abnormal fetuses with a normal karyotype. [1]
• Explains what microarray cannot detect: balanced rearrangements, low-level mosaicism, and single-nucleotide variants. [6]

Weak

• "A karyotype is the standard test." [1]
• Cannot explain the resolution difference between karyotype and microarray. [6]

Branch B — A variant of uncertain significance

Examiner: "The microarray returns, not a trisomy, but a variant of uncertain significance — a copy-number variant of unknown clinical significance. How do you counsel the family?" [6]

Strong

• States that a VUS is a real finding whose clinical meaning is genuinely not yet established by the scientific community — it is neither pathogenic nor benign. [6]
• Offers parental testing: if the VUS is inherited from an unaffected parent, incomplete penetrance is more likely; if de novo, it is more likely to be significant. [1]
• Plans database review (ClinGen, ClinVar), phenotype matching, and periodic reanalysis as knowledge accumulates. [6]
• Does not let the VUS drive irreversible decisions without further clarification. [6]

Weak

• "It is probably nothing, don't worry about it." [6]
• "This finding means your baby will have developmental delay." [6]

Branch C — Consanguinity and reproductive options

Examiner: "A different couple are first cousins and have had one child die of an undiagnosed neurodegenerative disorder. They are pregnant again. What reproductive options can you discuss?" [8]

Strong

• Estimates empirical recurrence risk: approximately 1 in 4 per pregnancy for an autosomal recessive condition, with first-cousin couples carrying an additional 2–3% excess risk above baseline. [7]
• Outlines the strategy to identify the gene: autozygosity mapping plus exome or genome sequencing using DNA from the affected child or both parents. [11]
• Presents the reproductive menu: PGT-M (IVF, embryo biopsy, testing for the familial mutation, transfer of unaffected embryos), prenatal diagnosis (CVS or amniocentesis with targeted testing) each pregnancy, donor gametes, and acceptance of risk. [8]
• Counsels honestly that PGT-M does not guarantee a live birth and that many programmes recommend prenatal confirmation. [8]

Weak

• "Consanguinity always causes problems; do not have more children." [7]
• Offers PGT-M without explaining the IVF requirement, cumulative cost or the allele drop-out limitation. [8]

Branch D — Confined placental mosaicism on CVS

Examiner: "Another patient had a CVS that reported mosaicism for trisomy 21. Is the fetus affected?" [4]

Strong

• CVS samples placental trophoblast, not fetal cells. Mosaicism on CVS may reflect confined placental mosaicism rather than the true fetal genotype. [4]
• Confirms with amniocentesis, which samples fetal cells in amniotic fluid and reflects the true fetal karyotype. [6]
• Explains that confined placental mosaicism occurs in approximately 1–2% of CVS samples and that over-calling it can lead to irreversible decisions based on non-representative tissue. [6]

Weak

• "Mosaicism on CVS means the baby has mosaic Down syndrome." [4]
• "Reassure the patient — placental mosaicism is always benign." [6]

Branch E — The paediatrician's role

Examiner: "A pathogenic 22q11.2 deletion is confirmed on microarray. As the paediatrician, what is your antenatal role?" [1]

Strong

• Translates the diagnosis into a postnatal plan: neonatal team readiness for cardiac evaluation, calcium monitoring, immune assessment and feeding evaluation. [1]
• Opens the multidisciplinary pathway: clinical genetics, paediatric cardiology and cardiac surgery, neonatology, immunology, and parent support. [6]
• Decides place and time of delivery at a centre with neonatal cardiac capability and ensures the neonatal team is alerted. [6]
• Holds the medical-home role: developmental surveillance, ongoing follow-up, and the family's continuity of care through birth and beyond. [6]

Weak

• "That is obstetrics; I will see the baby after birth." [6]
• Offers a single outcome narrative that ignores family values, available therapy and the variable expressivity of the syndrome. [1]