Mechanisms of Birth Defects

Question 1

Birth defects are the leading cause of death outside of _________ in the first year of life

Answer 1

prematurity

Question 2

Etiologies of birth defects

Answer 2

Unknown (40%), Multifactorial (25%), Environmental (10%), Chromosomal (15%), Monogenic (10%)

Question 3

Isolated (usual _________) and Sydnromic birth defects (usually chromosomal, monogenic, or teratogenic)

Answer 3

multifactorial

Question 4

determination of sexually dimorphic urogenital structures

Answer 4

First SRY gene on Y chromosome determines testes or not

Subsequent gene expression depends on presence/absence of testes, ultimately lead to sexual dimorphism

Question 5

cardiac development

Answer 5

First the cardiac tube forms and the first “switch” depends Shh expression –> determines rightward bend or leftward bend of cardiac tube

Also another hierarchical process in involved with cardiac neural crest

Question 6

Isolated (usual multifactorial) and Sydnromic birth defects (__________)

Answer 6

usually chromosomal, monogenic, or teratogenic

Question 7

Tetrology of Fallot

Answer 7

Pulmonary stenosis, RV hypertrophy, Overiding aorta, VSD

Genetics: mutation affecting gene expression in neural crest cells
• Most common is del22q11

Environment: Exposure to Vitamin A analogs creates a phenocopy that mimic the del22q11

Question 8

Known teratogens

Answer 8

thalidomide, Vitamin A analogues, statins, anticonvulsants, alcohol

Question 9

Produces phenocopy of chromosomal disorders; affects brain development; Growth retardation, dysmorphic, features, cognitive deficiencies

Answer 9

Fetal Alchohol Syndrome