Lect 9: Birth Defects

Question 1

Birth defects are

Answer 1

congenital malformations. Can be structural, behavioral, MALFORMATION of HEART is most common

Question 2

Single gene mutations can cause birth defects

Answer 2

often sporadic but can be inherited

Question 3

Chromosome defects alter embryonic development

Answer 3

aneupoloidy (except for Turners. Trisomy 21) or structural defects

Question 4

Mutations in single genes can alter the development of multiple systems

Answer 4

Axenfileld-Rieger Syndrome mutation is an example of a multisystem disorder caused by a single gene mutation

in PITX2 and FOXC1 which affects the eyes mainly. Things that cause people to not express the dz the same way: environment, modifying gene…susceptibility

Question 5

Holoprosencephaly

Answer 5

the most common malformation of the forebrain - results from failed or incomplete forebrain division…causing facial defects too. a wide spectrum of one dz.

Question 6

HPE pts have

Answer 6

-chromosomal abnormalities that include Trisomy 13, 18 -structural abnormalitites (deletions, duplications, mutation in a single gene
-environmental factors (maternal diabetes)
-single gene mutation
Genes in HPE operate in the hedgehog signaling pathway
-example of a birth defect that is caused by multiple things

Question 7

Environmental Factors and cause birth defects

Answer 7

Congenital Rubella Syndrome
Hyperthermia can interfere with neural tube closure
Drugs- thalidomide - the window of time that you are taking it

Question 8

Susceptibility to teratogens depends on several factors

Answer 8

1. genotype of the embryo - gene-environment interactions - mom’s genes give susceptibility or how to metabolize certain drugs. resistance to infect or whatever
2. developmental stage at the time of exposure
3. dose and duration of exposure

Question 9

Susceptibility varies with the developmental stage at the time of exposure. The most susceptible weeks for inducing birth defects is

Answer 9

weeks 3 - 8 during embryogenesis - because this is when organ development occurs

Question 10

Fetal Alcohol Syndrome

Answer 10

is the leading cause of mental retardation - philtrim

Question 11

AntiDepressants (SSRIs) during pregnancies have higher risks of

Answer 11

birth defects

Question 12

Summary

Answer 12

Infectious agents and pharmacological compounds can cross
the placenta and impact embryo development.
• Effects of teratogens depend on exposure and genetic
interactions.
• The embryonic period—weeks 3-8—is most susceptible to birth
defects.

Question 13

Septal Defects

Answer 13

• Atrial Septal Defects and VSDs…route of blood flow changes
• heart on the wrong side of the body (dextrocardia)

Question 14

Dectrocardia

Answer 14

if this occurs in the context of situs inversus totalis (mirror reversal of all organs then there will be little phenotypic consequence

Question 15

Heterotaxy can result in several congenital heart malformaions including

Answer 15

septal defects, double outlet right ventricle (DORV) and the transposition of the great arteries (TGA)

Question 16

DORV is

Answer 16

when the aorta arises from the right ventricle instead of the left ventricle. Both the pulmonary artery and aorta come from the same chamber and no arteries arise from the left ventricle. DORV always includes a VSD that helps the infant because oxygen-rich blood from the lungs flow from the L side of the heartm through the VSD opening and into the right chamber, mixing with the oxygen poor blood.

Question 17

TGA occurs whem

Answer 17

the two main arteries carrying blood out of the heart - the main pulmonary artery and the aorta are switched in position. The oxygen poor blood from the body enters the right side of the heart but instead of going to the lungs the blood is pumpred directly back out to the rest of the body through the aorta. Often babies with TGA have septal defects that allow blood to mix so that some oxygen rich blood can be pumped to the rest of the body

Question 18

Sympthoms of congenital heart defects include

Answer 18

rapid breathing, cyanosis, fatigue, poor blood circulation

Question 19

Heart defects in 22q11.2 deletion syndrome patients

Answer 19

teratology of Fallot and Truncus arteriosus

Question 20

Truncus Arteriosus or persistent truncus arteriosus (22q11.2 deletion)

Answer 20

defect in which a single common blood vessel comes out of the heart instead of the usual two vessels (pulmonary artery and aorta). They didn’t separate completely.

There is usually a VSD

Question 21

Tetrology of Fallot (22q deletion)

Answer 21

Four defects:
1. VSD
2. Pulmonary stenosis
3. overriding aorta - outflow tract
4. ventricular hypertrophy 
TBX 1 - plays a role in Neural crest development. So if you lose this TF you will get a mutation in TBX1 you will have problems in the outflow tract. This gene is located in the deletion region of chrom 22q

Question 22

Summary

Answer 22

Heart malformations are the most common birth defect.
• Defects in establishing laterality of the heart can result in a broad
spectrum of malformations.
• Patients with 22q11.2 deletion syndrome often have
malformations of the cardiac outflow tract that are likely caused
by defects in cardiac neural crest development.

Question 23

Q1.Holoprosenchephaly is associated with

Answer 23

all of these

1. single gene mutation
2. Trisomy 13
3. Maternal Diabetes
4. Fetal Alcohol Syndrome

Question 24

Q2. A woman had a fever in the 9th week of pregnancy. Could this have caused a neural tube defect?

Answer 24

No, because the tube is completely closed by the beginning of the 6th week of pregnancy. After the neural tube has closed, a NT defect cannot occur and the embryo is not at risk