Disorders Involving an Extra Autosome

DISORDERS INVOLVING AN EXTRA AUTOSOME

Down syndrome (trisomy 21).

The most common karyotype is 47, XX, +21. Down syndrome is the most common chromosomal disorders. The risk increases with maternal age to an incidence of 1 in 25 live births in women age ≥45. The pathogenesis involves meiotic nondisjunction (95%), Robertsonian translocation (4%), or mosaicism due to mitotic nondisjunction during embryogenesis (1%).

Clinical findings can include intellectual disability; mongoloid facial features (flatface, low-bridged nose, and epicanthal folds); Brushfield spots (speckled appearance of the iris); muscular hypotonia; broad short neck; palmar (simian) crease; and congenital heart defects. Endocardial cushion defect, if present, leads to the formation of an atrioventricular canal (a common connection between all 4 chambers of the heart). Additional clinical problems that can develop include duodenal atresia (“double-bubble” sign); Hirschsprung disease; increased risk (15–20 fold) of acute lymphoblastic leukemia (ALL); and Alzheimer disease (by age 40 virtually all will develop Alzheimer disease).

Prenatal tests include maternal serum tests, ultrasonography, amniocentesis, and chorionic villus sampling.

Median life expectancy is 47 years.