Down Syndrome (Trisomy 21)
| Category | Details & Clinical Pathophysiology |
|---|---|
| Etiology | ~95% Meiotic Nondisjunction (maternal); ~4% Robertsonian translocation; ~1% Mosaicism. Incidence increases significantly with maternal age. |
| Clinical Features | Flat facies, epicanthal folds, single palmar crease (Simian crease), gap between 1st/2nd toes, intellectual disability, and duodenal atresia. |
| Cardiac/Medical | Congenital heart defects (most commonly endocardial cushion defects/AV septal defects). Increased risk of ALL, Alzheimer’s (early-onset), and hypothyroidism. |
High-Yield Core Realities:
- Screening vs. Diagnostic: First-trimester screening includes nuchal translucency (increased) and serum markers (low PAPP-A, high $\beta$-hCG). Diagnostic testing (chorionic villus sampling or amniocentesis) is required for definitive karyotype confirmation.
- The Duodenal Connection: Duodenal atresia presents with the classic “double bubble” sign on abdominal X-ray. Always suspect Trisomy 21 in newborns with this presentation and bilious vomiting.
- Why Early-Onset Alzheimer’s? The gene for the Amyloid Precursor Protein (APP) is located on chromosome 21. The extra copy of this gene leads to overproduction of amyloid-beta, causing premature plaque deposition.
- Educational Resource: For comprehensive lecture notes, exam-style practice questions, and high-yield visual guides on pediatric genetics, visit mymedschool.org.