Clinical Applications of Genetic Testing
Core concepts
Understand indications for testing across the lifespan: prenatal (aneuploidy screening, cfDNA/NIPT, diagnostic amniocentesis/CVS), pediatric (developmental delay, congenital anomalies, metabolic disorders), adult (hereditary cancer, cardiovascular, neurodegenerative), and pharmacogenomics. Know screening vs diagnostic distinctions and the limitations of each.
Be familiar with hereditary cancer syndromes (BRCA1/2, Lynch/MMR, Li-Fraumeni/TP53), cardiovascular genetics (familial hypercholesterolemia, cardiomyopathies, channelopathies), and prenatal screening (first-trimester combined, cfDNA). Understand actionability - whether a result changes management - and the role of genetic counseling before and after testing.
Traps
Questions frequently test screening vs diagnostic confusion: NIPT is a screening test requiring diagnostic confirmation. Another trap: assuming a negative cfDNA result excludes all chromosomal abnormalities (it does not; it targets common aneuploidies). Watch for actionability assumptions - not all pathogenic variants change management. Also beware of variant interpretation in unaffected individuals (reduced penetrance, adult-onset conditions in minors).
Rule of thumb
Screening tests estimate risk; diagnostic tests establish it. Any positive screening result (NIPT, serum screen) should be confirmed by a diagnostic test (amniocentesis, CVS, or postnatal testing).
Worked example
A 35-year-old at 12 weeks has a high-risk cfDNA result for trisomy 21. cfDNA is a screening test; diagnostic confirmation via CVS or amniocentesis with karyotype/CMA is offered before irreversible decisions.