Prenatal Diagnosis and Genetic Counseling

Indications & Overview - Why & What We Test

• Purpose: Detect fetal conditions; enable informed choice & management.
• Indications (Why Test):
  • AMA (>35 yrs).
  • Previous child/family hx: genetic disorder/chromosome anomaly.
  • Parental carrier: chromosomal abnormality.
  • Abnormal screening: FTS, NIPT, Quad.
  • Ultrasound markers: ↑NT, structural defects.
• Scope (What We Test):
  • Chromosomal: Trisomies (21, 18, 13).
  • Single gene: Thalassemia, CF.
  • Structural: NTDs, cardiac.
• Genetic Counseling: Key for risk/benefit discussion, informed decisions.

⭐ Nuchal Translucency (NT) >3.5mm is a significant marker for aneuploidy (e.g., Trisomy 21) and fetal cardiac anomalies.

Screening Tests - Early Clues Hunt

• Goal: Identify ↑ risk for aneuploidy (e.g., Down syndrome) & NTDs. Non-diagnostic.
• First Trimester Combined (FTCS): 11 - 13$^{+6}$ wks
  • Serum: ↓ PAPP-A, ↑ free β-hCG (T21)
  • USG: ↑ Nuchal Translucency (NT)
  • DR T21: ~90%
• Second Trimester Quad Test: 15 - 22$^{+6}$ wks (opt. 16-18w)
  • Serum (T21): ↓ AFP, ↓ uE3, ↑ hCG, ↑ Inhibin A
    • 📌 T21: "HI" - hCG & Inhibin A are High.
  • ↑ AFP: NTDs.
  • DR T21: ~80%
• NIPT (cell-free fetal DNA): From 10 wks
  • Highest DR for common trisomies (T21 >99%).

⭐ NIPT (cffDNA): highest screening DR (>99% T21); positive results need diagnostic confirmation.

• USG Markers:
  • 1st Tri: NT, nasal bone.
  • 2nd Tri: Soft markers (e.g., EIF). A_IMAGE_PLACEHOLDER

Invasive Diagnostics - Confirming Suspicions

Confirmatory tests after abnormal screening or high-risk history. Pre-test counseling is vital. Rapid results (e.g., FISH for common aneuploidies) often available.

• Chorionic Villus Sampling (CVS)
  • Timing: 10-13 weeks gestation.
  • Method: Samples placental villi (transcervical/transabdominal).
  • Detects: Chromosomal abnormalities, genetic disorders (e.g., thalassemia). Does NOT detect NTDs.
  • Risk: Miscarriage ~0.5-1%; limb reduction defects if <10 weeks.
• Amniocentesis
  • Timing: Typically 15-20 weeks; can be done later.
  • Method: Samples amniotic fluid (fetal cells, biochemicals).
  • Detects: Chromosomal abnormalities, NTDs (AFP), lung maturity (L/S ratio), Rh isoimmunization.

  ⭐ Amniotic fluid acetylcholinesterase (AChE) is more specific for open NTDs than AFP.

  • Risk: Miscarriage ~0.1-0.3%.
• Cordocentesis (Percutaneous Umbilical Blood Sampling - PUBS)
  • Timing: Usually >18 weeks.
  • Method: Fetal blood from umbilical cord.
  • Uses: Rapid karyotyping, fetal anemia, infection, thrombocytopenia, fetal therapy.
  • Risk: Highest; ~1-2% miscarriage.

Genetic Counseling & Key Syndromes - Guidance & Genes

• Genetic Counseling:
  • Non-directive communication for informed choices, risk assessment, support.
  • Indications: Advanced Maternal Age (AMA >35y), +ve family Hx, abnormal screen/USG, teratogen, consanguinity.
• Key Aneuploidies (Chromosomal Abnormalities): 📌 Trisomy Ages: Down (21), Edwards (18), Patau (13).
  • Down (T21): Most common. ID, epicanthal folds, single palmar crease, CHD.
  • Edwards (T18): Severe. Clenched hands, rocker-bottom feet, micrognathia, CHD. Poor prognosis.
  • Patau (T13): Severe. Midline defects (holoprosencephaly, clefts), polydactyly, CHD. Poor prognosis.
  • Turner (45,X0): Female. Short stature, webbed neck, ovarian dysgenesis, coarctation.
  • Klinefelter (47,XXY): Male. Tall, gynecomastia, hypogonadism, infertility.

⭐ Non-Invasive Prenatal Testing (NIPT) using cell-free fetal DNA (cffDNA) is a highly sensitive screening test for common aneuploidies.

High‑Yield Points - ⚡ Biggest Takeaways

• First-trimester screening (Dual test, NT scan): 11-13+6 weeks for aneuploidy risk.
• Second-trimester screening (Quadruple test): 15-20 weeks, detects Down syndrome, NTDs.
• CVS: 10-13 weeks for early genetic diagnosis; slight risk of fetal loss.
• Amniocentesis: 15-20 weeks for genetic diagnosis; safer than CVS.
• NIPT (cfDNA): From 10 weeks; high sensitivity for common trisomies.
• Karyotyping: Gold standard for definitive diagnosis of chromosomal abnormalities.
• Autosomal recessive disorders: 25% recurrence risk with each pregnancy.