Down syndrome is the most common pattern of human malformation.
Genetics
94% full trisomy 21(nondisjunction); risk of recurrence 1–2% and then
increases with advancing maternal age
4–6% with translocation; most are new mutations but must obtain
parental karyotypes for possible balanced translocation carrier
Findings
Upward slanting palpebral fissures; speckling of iris (Brushfield
spots); inner epicanthal folds
Small stature, mouth open with tongue protrusion; mild microcephaly,
short neck, flat occiput, short metacarpals and phalanges; single palmar
crease
Hypotonia
Hearing loss (sensorineural, conductive, and mixed)
Primary gonadal deficiency
Cardiac anomaly—ECD > VSD > PDA, ASD; also MVP
GI anomalies: duodenal atresia, Hirschprung
Atlanto-axial instability
Hypothyroidism
Acute lymphocytic leukemia (but acute myeloblastic leukemia if in
first 3 years of life)
Mental retardation, variable
Natural history
Major cause for early mortality is congenital heart disease
Muscle tone improves with age
Rate of development slows with age
Early onset of Alzheimer disease