A 3-year-old child with Down syndrome is being evaluated for associated anomalies. Which of the following is NOT typically associated with trisomy 21?

Explanation

## Down Syndrome: Associated Anomalies ### Cardiac Defects in Trisomy 21 **Key Point:** Congenital heart disease occurs in ~40–50% of Down syndrome cases. The most common defects are: | Cardiac Anomaly | Frequency in DS | Notes | | --- | --- | --- | | AVSD (endocardial cushion defect) | 40–45% | Most characteristic; involves AV valves and septa | | VSD | 30–35% | Often muscular or perimembranous | | ASD | 10–15% | Secundum type | | PDA | 10–12% | Especially in premature infants | | Tetralogy of Fallot | 5–10% | Less common than AVSD | **High-Yield:** Atrioventricular septal defect (AVSD) is the **hallmark cardiac lesion** of Down syndrome—seen in ~40% of cases, far higher than in the general population. ### GI Anomalies in Trisomy 21 **Key Point:** Duodenal atresia is a classic association: - Occurs in ~1 in 2,500–4,500 live births overall - In Down syndrome, incidence is ~1 in 200–300 (8–10× higher) - Presents with polyhydramnios, bilious vomiting, "double bubble" sign on X-ray - Requires surgical bypass (duodenoduodenostomy) **Clinical Pearl:** Hirschsprung disease (aganglionosis of the colon) is **NOT** a recognized association with Down syndrome. It is, however, strongly associated with: - Trisomy 13 (Patau syndrome) - Trisomy 18 (Edwards syndrome) - Waardenburg syndrome - Multiple endocrine neoplasia type 2A (MEN 2A) ### Other Classic Down Syndrome Features - **Facial:** Flat facies, upslanting palpebral fissures, epicanthal folds, low-set ears - **Skeletal:** Hypotonia, short stature, clinodactyly (curved 5th finger), simian crease - **Hematologic:** Increased risk of acute leukemia (20-fold), especially ALL - **Endocrine:** Hypothyroidism, growth hormone deficiency - **Ophthalmic:** Refractive errors, cataracts, strabismus - **Hearing:** Conductive and sensorineural hearing loss **Warning:** Duodenal atresia and cardiac defects (especially AVSD) are so common in Down syndrome that screening is mandatory in all newborns with trisomy 21. Hirschsprung disease, by contrast, is not part of the standard Down syndrome phenotype. **Mnemonic: "AVSD-DUO"** — AVSD and DUodenal atresia are the two GI/cardiac hallmarks of Down syndrome.