Prenatal Diagnosis and Genetics
Core concepts
Understand aneuploidy screening: first-trimester combined screening, cell-free DNA, and the difference between screening and diagnostic testing. Know the indications for chorionic villus sampling and amniocentesis, their timing, and their procedure-related loss rates. Understand karyotype versus microarray and when microarray adds value (e.g., ultrasound anomalies with normal karyotype). Know the inheritance patterns of common conditions (autosomal recessive, autosomal dominant, X-linked) and the principles of carrier screening and preimplantation genetic testing.
Know the common microdeletion syndromes and their prenatal ultrasound associations. Understand fetal aneuploidy ultrasound markers (nuchal translucency, nasal bone, cardiac defects) and their limitations. Be familiar with teratogen counseling and the role of genetic counseling in recurrence risk.
Traps
- Confusing screening sensitivity with diagnostic certainty; cell-free DNA is not diagnostic.
- Forgetting that CVS does not detect neural tube defects; amniotic fluid AFP or maternal serum AFP is needed.
- Missing that microarray can detect copy-number variants that karyotype misses.
- Overlooking that carrier screening panels vary by ethnicity and family history.
- Assuming a normal karyotype excludes all genetic disease.
Rule of thumb
For any prenatal diagnostic question, ask: what is being tested (screening vs. diagnostic), what is the timing, and what are the limitations of the test? Then consider whether a confirmatory test is needed.
Worked example: A patient has an abnormal first-trimester screen and wants definitive information. Offer diagnostic testing with CVS (earlier) or amniocentesis (later), and explain that microarray may provide additional information if a structural anomaly is found.