Birth Defects

Question 1

What is birth defect synonymous with? What type of orders do these encompass at birth?

Answer 1

Congenital malformation; structural, behavioral, functiona, or metabolic disorders

Question 2

What are most birth defects caused by? What causes 20-25% of birth defects?

Answer 2

Unknown causes; gene and environment (multifactorial)

Question 3

What can birth defects be due to? How can it be inherited?

Answer 3

Due to single mutations, chromosomal abnormalities; often sporadic, but can be inherited as dominant, recessive, or X-linked

Question 4

What is an example of a mutation in single gene? Will a multisystem disorder always affect the same systems? What system will this disease affect primarily? What mutations lead to this syndrome?

Answer 4

Axenfeld-Rieger syndrome; no, not necessarily; Eyes; Pitx2 and FOXC1 genes, which help with formation of anterior eye

Question 5

What two things can determine disease severity? What are the two types of traits?

Answer 5

Gene-gene and gene-environment interactions; Mendelian (monogenic) vs. complex (multifactorial) with latter having several genes involved

Question 6

What is the reason behind holoprosencephaly? What are three causes of HPE?

Answer 6

Forebrain incompletely cleaves into right and left hemispheres; chromosomal abnormalities (number and structure), environmental factor (maternal diabetes) or single gene mutations

Question 7

What are several genes involved in holoprosencephaly?

Answer 7

SHH, PTCH1, GLI2, DISP1; HH is a ligand from inducer cell, DISP involved in inducer cell, PTCH a receptor on responder cell, GLI a TF in responder cell

Question 8

What can rubella viral infections (German measles) lead to? TORCH What can hyperthermia do?

Answer 8

Cataracts, patent ductus arteriosus, microcephaly; Interfere with neurulation and cause neural tube defects

Question 9

What can thalidomide lead to? What is it evidence for?

Answer 9

Limb malformations (phocomelia); drugs can cross placenta and affect embryo development

Question 10

What is teratology? What is a teratogen?

Answer 10

Study of birth defects; agents that cause birth defects (environmental)

Question 11

What can cause birth defects?

Answer 11

Drugs and chemicals; ionizing rads; hyperthermia (neurulation issues); infectious microorganisms; metabolic conditions in the mother

Question 12

What are key modulators of teratogen efficacy?

Answer 12

genotype of the embryo (or mom), developmental stage of exposure (3-8 weeks), dose and duration of exposure

Question 13

What is the most sensitive period for inducing birth defects? What systems can be affected? What is a problem for many women due to this knowledge?

Answer 13

Weeks 3-8 during embyrogenesis; CNS, heart, eyes; Many women unaware they are pregnant and won’t have prenatal visit until after week 8

Question 14

What is fetal alcohol syndrome? What is it the leading cause of? How much alcohol is needed to cause defects? What contributes to FASD severity?

Answer 14

severe form of FAS disorders; congenital mental retardation; Not clear how much is needed; Amount of alcohol, timing, genetics

Question 15

What is FAS characterized by?

Answer 15

Structural defects, growth deficiency, intellectual disability; small head, smooth philtrum, narrow upper lip, lose nose bridge

Question 16

What five processes can alcohol help interfere with?

Answer 16

Cell migration, proliferation, adhesion, survival, and signaling

Question 17

What is the most common birth defect? How severe is it? What are most cases attributed to? How can you get the same malformation?

Answer 17

Congenital heart defects; Broad range of severity; Multifactorial (some chromosomal abnormalities and teratogens); Several different developmental events

Question 18

What causes a “hole in the heart”? Where can these occur? What is the mech behind why this is so bad?

Answer 18

Septal defect; Atrial and ventricular septal defect; Mixing of oxygenated blood

Question 19

What is the condition of having the heart on the right side instead of the left?

Answer 19

Dextrocardia (heart laterality reversed)

Question 20

What are congenital heart defects associated with? What are three examples?

Answer 20

Laterality defects; Septal defects (e.g. dextrocardia with atrial septal defects), double outlet right ventricle (VSD included, no arteries arise from LV), transposition of the great arteries (aorta and pulmonary artery position switched)

Question 21

What are signs and symptoms of severe heart defects?

Answer 21

Rapid breathing, cyanosis, fatigue, poor blood circulation

Question 22

What type of syndrome is 22q11.2 deletion syndrome? How much is deleted? What kind of heart malformations can this include?

Answer 22

Heterogeneous multisystem syndrome; 3 MB deletion on chromosome 22 (30-40 genes) tetralogy of Fallot, truncus arteriosus

Question 23

What gives rise to the great arteries? What is associated with truncus arteriosus (2 things)? What is the tetralogy of Fallot and what four things does it include?

Answer 23

Cardiac outflow tract; VSD and truncal valve (instead of an aortic and pulmonary valve); PDRV

Question 24

What can lead to the defects of truncus arteriosus and tetraology of Fallot?

Answer 24

Deletion in 22q11.2 region (TBX1) that regulate cardiac NCC’s normally during development