Teratology

Teratology - Birth Defect Blueprint

• Teratology: Study of abnormal development & birth defects.

• Teratogen: Agent causing birth defects (e.g., drugs, infections).

• Types of Defects:

  • Malformation: Primary structural defect (e.g., VSD).
  • Deformation: Abnormal form from mechanical force (e.g., clubfoot).
  • Disruption: Breakdown of normal tissue (e.g., amniotic bands).
  • Dysplasia: Abnormal cell organization in tissue (e.g., skeletal dysplasia).

• Wilson's Principles (Key Aspects):

  • Susceptibility: Genotype-dependent (embryo/mother).
  • Critical Periods: Organogenesis (3-8 weeks) for major anomalies; later for functional/minor defects.
  • Dose-Response: ↑ dose → ↑ effect; threshold often exists.
  • Specific Mechanisms: Teratogens act via specific pathways.
  • Manifestations: Death, malformation, growth restriction, functional issues.

⭐ The embryonic period (weeks 3-8) is the most critical for teratogenic insults, leading to major structural anomalies.

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Teratology - Developmental Saboteurs

Teratogens are agents causing congenital malformations. Susceptibility is highest during organogenesis (3rd-8th week).

• A. Drugs:
  • Thalidomide: Phocomelia
  • Warfarin: Chondrodysplasia punctata, nasal hypoplasia
  • Valproic acid: Neural Tube Defects (NTDs)
  • ACE inhibitors: Renal tubular dysgenesis, oligohydramnios
  • Isotretinoin: Craniofacial, cardiac, CNS defects
  • Lithium: Ebstein's anomaly
  • Methotrexate: Skeletal, CNS defects
  • Phenytoin: Fetal hydantoin syndrome
• B. Infections (📌 TORCH):
  • Toxoplasmosis: Chorioretinitis, hydrocephalus, intracranial calcifications
  • Other: Syphilis (Hutchinson's teeth), VZV (limb hypoplasia), Parvovirus B19 (hydrops fetalis)
  • Rubella: Cataracts, deafness, Patent Ductus Arteriosus (PDA)
  • CMV: Microcephaly, periventricular calcifications
  • Herpes (HSV): Skin vesicles, encephalitis
• C. Maternal Conditions:
  • Diabetes mellitus: Caudal regression, cardiac defects, NTDs
  • PKU: Microcephaly, intellectual disability
  • Hypo/Hyperthyroidism: Cretinism (hypo), developmental issues
• D. Physical Agents:
  • Ionizing radiation (>5 rads): Microcephaly, intellectual disability
  • Hyperthermia: NTDs, cardiac defects
• E. Alcohol:
  • Fetal Alcohol Syndrome (FAS): Facial anomalies, growth restriction, CNS dysfunction

⭐ Valproic acid taken during pregnancy significantly increases the risk of neural tube defects, particularly spina bifida.

Teratology - Syndrome Spotting & Shielding

• Key Teratogenic Syndromes:

  • Fetal Alcohol Syndrome (FAS):
    • Characteristic facies: Smooth philtrum, thin upper lip, small palpebral fissures (📌 Smooth, Thin, Small - STS).
    • Growth retardation, CNS (microcephaly, intellectual disability).
  • Valproate Embryopathy: ↑Risk of NTDs (esp. spina bifida), cardiac & limb defects, developmental delay.
  • Diabetic Embryopathy: Macrosomia, cardiac defects (VSD, TGA), CNS (NTDs), sacral agenesis (caudal regression).

• Neural Tube Defects (NTDs): Anencephaly, spina bifida.

  • Prevention: Folic acid (0.4mg/day general; 4mg/day high-risk e.g., previous NTD).

  ⭐ Pre-conceptional folic acid supplementation is crucial for preventing neural tube defects.

• Prenatal Diagnosis:

  • Maternal Serum Screening:
    • 1st Trimester: Dual test (PAPP-A, β-hCG).
    • 2nd Trimester: Quadruple screen (AFP, hCG, Estriol, Inhibin A - 📌 All Happy Elephants Initiate).
  • Ultrasound: Nuchal Translucency (NT), Anomaly scan.
  • Invasive Tests (Diagnostic): Amniocentesis, Chorionic Villus Sampling (CVS).

• Prenatal Screening Flow:

High‑Yield Points - ⚡ Biggest Takeaways

• TORCH infections (Toxoplasmosis, Rubella, CMV, HSV, Syphilis) are major causes of congenital malformations.
• The critical period for teratogen exposure is weeks 3-8 of gestation (organogenesis).
• Thalidomide is linked to phocomelia; Valproic acid to neural tube defects.
• Fetal Alcohol Syndrome (FAS) features include facial dysmorphism, growth restriction, and CNS dysfunction.
• ACE inhibitors are teratogenic, causing renal anomalies and oligohydramnios.
• Maternal diabetes is a risk factor for congenital heart disease and caudal regression syndrome.