Incidence, 1 in 650-1000 live births

Etiology:

 trisomy 21

• Meiotic origin >95% maternal, mostly meiosis I - Increased recurrence risk with parental translocation
• Full trisomy 21: 94%
• Mosaic trisomy 21: 2.4%
• Translocation 21: 3.3%

Synopsis

 systemic anomalies

• short stature

 head and neck anomalies

• brachycephaly
• excess nuchal skin
• flat facial profile
• small ears
• folded helix
• conductive hearing loss
• upslanting palpebral fissures
• epicanthal folds
• cleft lip/cleft palate
• cataracts
• iris brushfield spots
• protruding tongue

 cardiovascular anomalies (50%)

• cardiac malformations
  • atrioventricular canal

• pulmonary hypertension
• pulmonary capillary dysplasia
• pulmonary vascular sclerosis
• coronary periarteritis nodosa

 digestive anomalies

• oesophageal atresia (1%)
• duodenal stenosis/duodenal atresia (30%)
• imperforate anus and anorectal malformations (2%)
• Hirschsprung disease (congenital megacolon) (2%)
• annular pancreas (24%)

 hepatic anomalies

• neonatal hemochromatosis +/- transitory leukemoid reaction

 renal anomalies

• renal tubular dysgenesis

 rachis anomalies

• atlanto-axial instability

 limbs anomalies

• hypoplastic iliac wings
• shallow acetabulum
• joint laxity
• short hands, broad hands
• fifth finger mid-phalanx hypoplasia
• single transverse palmar crease
• talipes equinovarus

 neurological anomalies

• mental retardation
• Alzheimer disease
• hypotonia, poor Moro reflex
• meningomyelocele

 endocrine anomalies

• hypothyroidism

 hematological anomalies

• leukemoid reaction +/- neonatal hemochromatosis
• leukemias (both ALL and AML)
  • acute megakaryocytic leukemia

 autoimmunity

• thyroid dysfunction (#2149955#)

References

 Patterson D, Costa AC. Down syndrome and genetics - a case of linked histories. Nat Rev Genet. 2005 Feb;6(2):137-47. PMID: #15640809#

 Hitzler JK, Zipursky A. Origins of leukaemia in children with Down syndrome. Nat Rev Cancer. 2005 Jan;5(1):11-20. PMID: #15630411#

 Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S. Chromosome 21 and down syndrome: from genomics to pathophysiology. Nat Rev Genet. 2004 Oct;5(10):725-38. PMID: #15510164#

 Hernandez D, Fisher EM. Down syndrome genetics: unravelling a multifactorial disorder. Hum Mol Genet. 1996;5 Spec No:1411-6. PMID: #8875245#