Congenital Anomalies

Intro & Causes - Blueprint Blips

• Congenital Anomalies (CA): Structural/functional defects from intrauterine life. Affect ~2-3% live births.
• Classification - "Blueprint" Errors:
  • Malformation: Intrinsic error in morphogenesis (e.g., NTDs). Primary "blueprint" flaw.
  • Disruption: Extrinsic factor damages normal tissue (e.g., amniotic bands). "Blueprint" torn.
  • Deformation: Mechanical forces distort (e.g., clubfoot). "Blueprint" warped.
  • Dysplasia: Abnormal cell/tissue organization (e.g., skeletal dysplasias). Faulty "materials".
• Major Causes:
  • Genetic (~20-30%): Chromosomal (Trisomy 21), gene mutations.
  • Environmental (Teratogens, ~10%): TORCH, maternal diabetes, drugs (alcohol), radiation.
  • Multifactorial (~20-30%).
  • Unknown (~40-60%).

⭐ Peak teratogen susceptibility: organogenesis (3rd-8th week gestation).

Teratogens - Womb Wreckers

Agents causing birth defects. Max risk: 3-8 weeks (organogenesis). Effect: dose, timing, genetics dependent.

• TORCH Infections:
  • Toxoplasmosis: Chorioretinitis, hydrocephalus, intracranial calcifications.
  • Other: Syphilis (Hutchinson's teeth), Varicella-Zoster Virus (VZV) (limb hypoplasia), Parvovirus B19 (hydrops fetalis).
  • Rubella: Cataracts, deafness, Patent Ductus Arteriosus (PDA).
  • Cytomegalovirus (CMV): Microcephaly, periventricular calcifications. (Most common congenital infection)
  • Herpes Simplex Virus (HSV): Skin vesicles, encephalitis.
• Key Drugs:
  • ACE inhibitors (ACEi): Renal defects, oligohydramnios.
  • Warfarin: Nasal hypoplasia, bone stippling (chondrodysplasia punctata).
  • Valproate: Neural Tube Defects (NTDs).
  • Phenytoin: Fetal Hydantoin Syndrome (craniofacial defects, hypoplastic nails).
  • Lithium: Ebstein's anomaly.
  • Isotretinoin (Vitamin A): CNS, facial, cardiac defects. ⚠️ Highly teratogenic!
  • Thalidomide: Phocomelia (limb reduction defects). 📌 Thali-LIMB-omide
  • Alcohol: Fetal Alcohol Syndrome (FAS) (facial dysmorphism, growth & CNS issues).
• Radiation: Microcephaly, Intellectual Disability (ID).
• Maternal Conditions:
  • Diabetes Mellitus: Caudal regression syndrome, Ventricular Septal Defect (VSD), macrosomia.
  • Phenylketonuria (PKU) (uncontrolled): Microcephaly, ID, cardiac defects.

⭐ Valproate taken during pregnancy increases the risk of neural tube defects (e.g., spina bifida) by approximately 1-2%.

Systemic Anomalies - Organ Outliers

• Cardiovascular System:
  • Ventricular Septal Defect (VSD): Most common congenital heart defect.
  • Tetralogy of Fallot (TOF): 📌 PROVe (Pulmonary stenosis, RVH, Overriding aorta, VSD).
  • Transposition of Great Arteries (TGA): Requires PGE1 to maintain ductus arteriosus patency.
• Gastrointestinal System:
  • Tracheoesophageal Fistula (TEF): Often with esophageal atresia.
  • Pyloric Stenosis: Projectile non-bilious vomiting, palpable olive-mass.
  • Hirschsprung's Disease: Aganglionic megacolon; failure of neural crest cell migration.
• Renal System:
  • Horseshoe Kidney: Fusion of lower poles; trapped by inferior mesenteric artery.
  • Polycystic Kidney Disease (PKD): Autosomal dominant (adult) or recessive (infantile).
• Central Nervous System:
  • Anencephaly: Failure of anterior neuropore closure.
  • Spina Bifida: Failure of posterior neuropore closure.

⭐ Most common congenital anomaly of the GI tract is Meckel's diverticulum, often remembered by the rule of 2s (2% population, 2 feet from ileocecal valve, 2 inches long, 2 types of ectopic tissue).

Diagnosis & Prevention - Defect Detectives

• Prenatal Screening (Risk):
  • Serum Markers:
    • 1st Trimester: Dual (PAPP-A, β-hCG).
    • 2nd Trimester: Triple (AFP, β-hCG, uE3), Quad (+Inhibin A).
  • USG: NT (11-14 wks), Anomaly Scan (18-20 wks).
  • NIPT (cfDNA): High-risk aneuploidy detection (from 10 wks).
• Prenatal Diagnosis (Confirmatory):
  • CVS (10-13 wks).
  • Amniocentesis (15-20 wks).
• Prevention:
  • 📌 Folic Acid: 0.4mg/day (general); 4mg/day (high-risk NTD history).
  • Avoid Teratogens: TORCH, drugs (e.g., valproate), alcohol, radiation.
  • Genetic Counseling.
  • Maternal Health Optimization (DM, Hypothyroidism).

⭐ Maternal serum AFP (MSAFP): ↑ in open NTDs, abdominal wall defects; ↓ in Down syndrome.

High‑Yield Points - ⚡ Biggest Takeaways

• Neural tube defects (NTDs) like anencephaly & spina bifida are linked to folate deficiency.
• Congenital heart defects are most common; Ventricular Septal Defect (VSD) is most frequent.
• TORCH infections (Toxoplasmosis, Other, Rubella, CMV, Herpes) cause diverse birth defects.
• Fetal Alcohol Syndrome (FAS) shows facial dysmorphism, growth issues, and CNS problems.
• Down syndrome (Trisomy 21): most common chromosomal disorder, causes intellectual disability, distinct features.
• Potter sequence: due to oligohydramnios (e.g., renal agenesis), causes pulmonary hypoplasia, limb defects.