Epidemiology

Most common viable autosomal chromosome aberration (∼ 1:700 live births) and most common genetic cause of cognitive impairment
The risk of a Down syndrome pregnancy increases with maternal age.
- Incidence at 20 years: ∼ 1:2000
- Incidence at 45 years: ∼ 1:30

Etiology

Definition: three complete copies of chromosome 21 are present in all cells, with a total of 47 chromosomes
Pathogenesis: meiotic nondisjunction
Karyotype: ♀: 47,XX,+21 or ♂: 47,XY,+21

Definition: three copies of chromosome 21 are present, one of which is attached to another chromosome, usually chromosome 14 (less likely attached to chromosomes 13, 15, or 22)
Pathogenesis and karyotype
- Balanced Robertsonian translocation: translocation of the long arm of chromosome 21 to the long arm of chromosome 14. Not symptomatic, but can affect future generations
- Unbalanced Robertsonian translocation: clinical features of trisomy 21 caused by inheritance of a translocation chromosome and a normal chromosome

Definition: two cell lines are present, the trisomy 21 cell line and the normal cell line
Phenotypic expression varies according to the ratio of healthy to trisomic cells.

Eyes
- Upward-slanting palpebral fissures
- Epicanthal folds
- Ocular hypertelorism: a distance between the eyes greater than the 95th percentile
- Brushfield spots: an aggregation of connective tissue in the periphery of the iris, visible as white or grayish-brown spots.
Hypoplastic nasal bones, broad and flat nasal bridge

Extremities
- Transverse palmar crease: single crease that runs across the palm, along the metacarpophalangeal joints perpendicular to the fingers
- Sandal gap: a medial displacement of the first toe leading to a large space between the first and second toes
- Clinodactyly: abnormal curvature of a finger (typically refers to inward curvature of the 5th finger)
Skeletal features
- Atlantoaxial instability
- Short stature