Developmental Abnormalities

Teratology Principles - Agents of Chaos

• Teratology: Study of birth defects. Teratogen: Agent causing malformations.
• Key Principles (Wilson's):
  • Susceptibility (genotype, timing).
  • Specific mechanisms.
  • Dose-response relationship.
  • Outcomes: Death, malformation, growth issues, functional deficits.
• Critical Periods:
  • 3rd-8th week (organogenesis): Peak sensitivity.
  • <3rd week: All-or-none.

  • 8th week (fetal): Growth/functional defects.

• Teratogens: Drugs (e.g., thalidomide), Infections (TORCH), Radiation, Maternal factors (diabetes).

⭐ The most critical period for teratogenesis is the 3rd to 8th week of gestation (embryonic period/organogenesis).

Neural Tube Defects - Brainy Blunders

• Failure of neural tube (NT) closure (3rd-4th week gestation).
• Risks: Folic acid deficiency, maternal diabetes, valproate.
• Prevention: Folic acid 0.4 mg/day (general), 4 mg/day (prior NTD).
• Diagnosis: ↑AFP (maternal serum/amniotic fluid), ↑AChE (amniotic fluid), ultrasound.
• Types:
  • Anencephaly: No forebrain/skull vault; polyhydramnios.
  • Encephalocele: Brain/meninges herniation via skull defect.
  • Spina Bifida:
    • Occulta: Vertebral defect, asymptomatic, hairy patch/dimple.
    • Meningocele: Meninges + CSF herniation.
    • Myelomeningocele: Meninges + neural tissue; neuro deficits, Arnold-Chiari II common.

⭐ Anencephaly is characterized by absence of the forebrain and calvarium, and is incompatible with life.

Congenital Heart Defects - Broken Hearts

⭐ Ventricular Septal Defect (VSD) is the most common congenital heart defect overall.

• CHDs: Structural defects of heart/great vessels present at birth due to abnormal embryogenesis. Key classification based on presence or absence of cyanosis.

-   **P**ulmonary stenosis
-   **R**ight ventricular hypertrophy (RVH)
-   **O**verriding aorta
-   **V**entricular septal defect (VSD)

• Boot-shaped heart on CXR (ToF).

GI & GU Anomalies - Gut & Groin Goofs

• Gut Rotation & Wall Defects:
  • Malrotation: Ladd's bands, volvulus risk.
  • Omphalocele: Midline, sac-covered, ↑AFP, associated anomalies.
  • Gastroschisis: Right of umbilicus, no sac, ↑AFP, isolated.
• Atresias & Stenosis:
  • Duodenal atresia: "Double bubble" sign, Down syndrome.
  • Pyloric stenosis: Non-bilious projectile vomiting, palpable olive.
• GU Anomalies:
  • Hypospadias: Ventral meatus. Epispadias: Dorsal meatus.
  • Horseshoe kidney: Fused inferior poles, trapped by IMA.
  • 📌 POTTER sequence: Pulmonary hypoplasia, Oligohydramnios, Twisted face/skin, Extremity defects, Renal agenesis.

⭐ Meckel's diverticulum: Rule of 2s (2% pop, 2ft from ICV, 2in long, 2% symptomatic, 2 types ectopic tissue - gastric/pancreatic).

Craniofacial & Limb Defects - Awkward Arms & Faces

• Craniofacial Defects:
  • Cleft Lip: Failure of maxillary & medial nasal prominences to fuse.
  • Cleft Palate: Failure of palatal shelves to fuse.
  • Craniosynostosis: Premature cranial suture fusion (e.g., scaphocephaly).
  • Holoprosencephaly: Incomplete forebrain division; severe facial anomalies.
• Limb Defects:
  • Amelia: Complete limb absence.
  • Meromelia: Partial limb absence.
  • Phocomelia: Hands/feet near trunk (📌 Seal limbs); e.g., thalidomide.
  • Syndactyly: Fused digits.
  • Polydactyly: Extra digits.

⭐ Cleft lip results from failure of fusion of the maxillary prominence with the medial nasal prominence.

High‑Yield Points - ⚡ Biggest Takeaways

• Neural tube defects (NTDs) are linked to maternal folate deficiency.
• TORCH infections are major causes of congenital malformations.
• Fetal Alcohol Syndrome presents with characteristic facial dysmorphism and growth restriction.
• Down syndrome (Trisomy 21), commonest aneuploidy, causes intellectual disability, cardiac defects.
• Potter sequence from oligohydramnios causes pulmonary hypoplasia, limb deformities.
• DiGeorge syndrome (22q11.2 deletion): features CATCH-22 (Cardiac, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia).
• Teratogens cause defects during critical periods of organogenesis (e.g., thalidomide, phocomelia).