Mechanisms of Birth Defects

Question 1

What are the most common etiologies of birth defects?

Answer 1

• Unknown (40%)
• Multifactorial (20%)
• Chromosomal abnormalities (15%)
• Mendelian (10%)
• Maternal disease (10%)
• Infections and drugs (5%)

Question 2

Molecules less than ____________ can generally cross the placenta.

Answer 2

500 Daltons

Question 3

Describe the differences between malformation, deformation, and disruption.

Answer 3

• Malformation: morphologic or structural abnormality due to an intrinsic process
• Deformation: morphologic or structural abnormality due to a mechanical force
• Disruption: destruction or damage of normally developing tissue (such as ischemia or amniotic bands)

Question 4

What are amniotic bands?

Answer 4

Amniotic membranes getting stuck to the fetus

Question 5

Describe Potter sequence.

Answer 5

Renal agenesis leads to lack of urine into amniotic cavity. The lack of fluid in the cavity leads to uterine pressure on the fetus. This presses the feet, and hands, and face, leading to deformation. Pulmonary hypoplasia also resuts since fluid is needed for lung development.

Question 6

In addition to impaired development of the 3rd and 4th pharyngeal pouches, _____________ is also impaired in DiGeorge syndrome.

Answer 6

neural crest migration (hence the tetralogy of Fallot)

Question 7

What is a phenocopy?

Answer 7

A phenocopy is a disorder that mimics a genetic disorder. For instance, isotretinoin during pregnancy can lead to a phenotype like DiGeorge.

Isotretinoin inhibits TRX1 –the same gene defective in DiGeorge.

Question 8

What is the classic example of association defect?

Answer 8

Association defects are defects that are not contiguous or related by a known mechanism but that appear simultaneously more often than would be expected by chance. The most common is VACTERL: vertebral, anal, cardiac, tracheal, esophageal, renal, and limb.

Question 9

To cause the full complement of congenital Rubella syndrome, the virus must infect the fetus during ______________.

Answer 9

the first trimester

Question 10

Neural tube defects are multifactorial. What things can cause them?

Answer 10

• Insufficient intake of folic acid
• Maternal mutations in methyltetrahydrofolate reductase
• Folate antagonists (methotrexate)
• NTDs run in families, likely pointing to other genetic causes

Question 11

What is the prevalence of birth defects?

Answer 11

5% - 7% of the population has some kind of birth defect

Question 12

Although the placenta is able to detoxify most toxins, it does convert some chemicals to toxic forms: for example, __________.

Answer 12

caffeine