Last updated 3mo ago
A prenatal ultrasound at 12 weeks reveals increased nuchal translucency, absent nasal bone, and echogenic bowel. First trimester screening shows elevated risk for trisomy 21.
Chromosomal basis of Down syndrome (per AAP guidelines):
| Mechanism | % of cases | Karyotype (female) | Recurrence Risk |
|---|---|---|---|
| Meiotic nondisjunction | 96% | 47,XX,+21 | ~1% or age-related |
| Robertsonian translocation | 4% | 46,XX,rob(14;21),+21 | See below |
| Mosaicism | 1% | 46,XX/47,XX,+21 | <1% |
Meiotic nondisjunction: 95% occur in egg (maternal). Risk ↑ with maternal age (1:1000 at 30 y, 1:100 at 40 y). Recurrence risk 1% until maternal age risk exceeds 1% (around age 40).
Robertsonian translocation: Usually chromosome 21 attached to chromosome 14, 21, or 22. Obtain parental karyotypes to determine if de novo or inherited:
- 2/3 de novo (neither parent carrier) → ~1% recurrence risk
- 1/3 inherited from balanced carrier parent
- rob(14;21): If mother is carrier: 10-15% recurrence; if father is carrier: 2-5% recurrence (~90% of inherited cases come from carrier mothers, due to higher empiric transmission risk and reduced male-carrier fertility)
- rob(21;21): If either parent is a carrier → 100% recurrence (all viable offspring affected)
Mosaicism: Post-zygotic mitotic nondisjunction. Variable phenotype depends on proportion of trisomic cells. Medical complications fewer and intellectual disability often less severe. Recurrence risk <1% since parents are karyotypically normal.
Partial trisomy: Duplication of segment of chromosome 21 (extremely rare).
- Characteristic facies: upslanting palpebral fissures, epicanthal folds, flat nasal bridge, small ears
- Hypotonia in infancy
- Intellectual disability (mild to moderate)
- Congenital heart defects (~50%): AVSD most characteristic
- Increased risk: leukemia (ALL, AML), Hirschsprung disease, hypothyroidism, atlantoaxial instability
- Prenatal: positive cfDNA screening test → diagnostic amniocentesis/CVS with karyotype
- Prenatal: maternal serum screening: hCG and inhibin A elevated; PAPP-A, AFP, estriol decreased
- Postnatal: clinical features + karyotype
- Echocardiogram at birth
- Thyroid function monitoring
- Early intervention (for ages 0-3 years)
- AAP health supervision guidelines for Down syndrome (Pediatrics 2022)
The 5 A's of Down syndrome: Advanced maternal age, Atresia (duodenal), Atrioventricular septal defect (endocardial cushions), Alzheimer disease (early onset), AML/ALL.
"Hi" is high in Down: On maternal serum screening, hCG and inhibin A are elevated ("Hi"). Everything else is down: PAPP-A, AFP, and estriol are all decreased.