Mechanisms of Birth Defects Flashcards
Definition of a birth defect
Abnormality of structure, function or metabolism present at birth that results in physical or mental disabilities or death.
Birth defects are the leading cause of ___ outside of ___ in the first year of life
Leading cause of death outside of prematurity
What are the etiologies of birth defects?
- Unknown - 40%
- Multifactorial - 25%
- Environmental - 10%
- Chromosomal - 15%
- Monogenic - 10%
Xenobiotics
Compounds foreign to nature
What is a “critical period”?
A key point of development of specific structures during embryogenesis
Embyrologists are now dissecting ____ pathways of development and _____ _____ that determine organogenesis and mechanisms of birth defects
Hierarchical pathways of development and developmental fields
Ex: Determination of sexually dimorphic urogenital structures
What are developmental fields? How can they be organized
They are ways of thinking about structures (they are not tangible)
- Tissues sharing gene expression
- Tissues related to each other through location
- Tissues sharing developmental timing
- Tissues affected by interacting processes
Give an example of each of the different ways of organizing developmental fields
Tissues sharing gene expression: Hedgehog signaling pathways
Tissues related to each other through location: Branchial arches
Tissues sharing developmental timing: Embryonic inner cell mass
Tissues affected by interacting processes: Cell proliferation and apoptosis
VACTERL
Stands for all the stuff that occurred more frequently than can be accounted for by chance alone
V = Vertebral anomalies A = Anal atresia C = Cardiac anomalies (primarily septal defects) TE = Tracheal esophageal fistula and Esophageal atresia R = Renal L = Limb (predominantly radial upper limb) anomalies
Can phenotypes be generated solely by the effects of the environment OR genes?
No! They ALWAYS are the result of interactions between environment and genes.
Threshold model
Divides populations by genetic risks that are modified by the environment in a “dose” dependent fashion. Once you reach the “threshold”, then you are far more likely to have the specific birth defect.
Mutations associated with TOF
del 22q11 = 40%
JAG1 = 20%
Phenocopy
Similar birth defects resulting from a predominantly genetic or predominantly environmental factors
Why do we seem to think that Trisomy 21 is the most common trisomy?
Because we are biased by what we can see. The most common trisomy is actually 16, but they are all fatal and so we do not see any of those fetuses living.
Teratogens
Exogenous agents (physical or chemical) that disrupt developmental pathways causing birth defects
