Definition (Lancet 2003;361:1281; Am Fam Physician 1999;59:381)
• Down’s syndrome; most common genetic syndrome. 1:800–1,000 live births
• Congenital heart disease, myelodysplasia in newborn and duodenal atresia highly specific for Trisomy 21
• 95% 2/2 nondisjunction (nonsegregation) chromo 21 in oocyte or spermatocyte
• 4–5% caused by translocation of one chromosome 21 to another
• 1% of cases are mosaics (nondisjunction occurring after conception)
Diagnosis
• At birth: Constellation of features and confirmation by karyotype
• Prenatal: Quad screen: Maternal α-fetoprotein & Estriol lower than nml and β-HCG & Inhibin A higher (70–84% sensitivity)
• Fetal US w/ nuchal translucency, short femurs, cardiac anomalies, and duodenal atresia
• Women >35 yo w/increased risk. Chorionic villus sampling can be done btw 9 and 11 wk gestation, amnio btw 16 and 18 wk. Fetal cells examined for chromosomal abn
• Physical attributes: Hypotonia, flat face, upward/slanted palpebral fissures, epicanthic folds, Brushfield spots, mental retardation, cardiac malformations, simian crease
Complications
• Congenital heart disease: 40–60% of infants → ECG and TTE
• Complete AV canal defects (60% of heart defects); VSD (32%); TOF (6%)
• GI defects: Esophageal atresia, TEF, pyloric stenosis, duodenal atresia, Meckel, Hirschsprung, imperforate anus, and GERD; 5–15% w/ Celiac dz
• ENT: Midfacial malformations interfere with nml drainage of Eustachian tube and sinuses
• Recurrent otitis media, sinusitis, and pharyngitis
• Orthopedic:
• Atlanto-occipital instability, hyperflexibility, scoliosis
• Atlantoaxial instability: 13% asymp & need monitoring. No contact sports
• Late hip dislocation (>2 yo), SCFE, patellar subluxation or dislocation, foot deformities
• Thyroid dz followed by yearly TSH. GH def and gonadal dysfunction may also be present
• Congenital cataracts and other eye disease
• Transient myeloproliferative disorder (leukemoid reaction) in 10% of newborns (rare in non-Down’s infants). Increased risk of ALL
• Seizure disorder in 5–10%
• Dental problems and feeding difficulties
• Refer for early intervention to help with development