Birth defects Flashcards
Major causes of birth defects (top 4)
- Unknown (40%)
- Multifactorial (25%)
(polygenic) - Chromosomal (15%)
- Monogenic (10%)
Mesonephric duct forms what?
- ductus deferens,
- seminal vesicle,
- Epididymis
VACTERL mneumonic for anatomic abnormalities that are more frequently associated with eachother
Vertebral anomalies Anal atresia Cardiac anomalies Tracheo- Esophageal fistula Renal Limb
Birth defects are found in what % of the total population (children –> adults?)
5-7%
*about 2% of infants are born with life threatening birth defects
Birth defects are the leading cause of _______
death outside of prematurity in the 1st year of life
Teratology
- what is it?
- What does it focus on?
the study of birth defects and the mechanisms responsible for them
- focus on “critical periods” of developmental susceptibility
- great picture in handout
Most common trisomy
trisomy 16, but they dont survive
Phocomelia is caused by what?
Specific limb defects
- Thalidomide before 5 weeks
Teratogens
- Thalidomide
- Vit A analogs
- Cholesterol synth inhibitors
- Anticonvulsants
- ACE inhibitors
- Ethylalcohol
*exogenous agents that disrupt developmental pathways causing birth defects
Give examples of:
- Tissues sharing gene expression
- Tissues related to each other thru location
- Tissues sharing developmental timing
- TIssues affected by interacting processes
- Tissues sharing gene expression
- Hedgehog signaling pathway - Tissues related to each other thru location
- branchial arches - Tissues sharing developmental timing
- embryonic inner cell mass - TIssues affected by interacting processes
- cell proliferation and apoptosis
Are phenotypes the result of intxns btwn environment or genetic factors?
both - duh
phenocopies
similar birth defects resulting from predominantly genetic or predominantly evironmental factors
*anything produced by genetic mutations can also be produced by environmental manipulations
Xenobiotics
compounds foreign to nature
- kill cells by directly causing toxicity by apoptotic pathways or disrupt surface intxn with other cells
- Depending on number of certain cells affected –> recognizable syndromes
Tetrology of fallot
- Supravalvular pulmonic stenosis
- Overridig aorta
- VSD
- RV hypertrophy
Most common genetic (chromosomal) mutation associated with TOF
- what other genetic syndromes are associated with ch 22?
- What environmental factor increases the risk of TOF?
deletion on ch 22q11
- associated with Shprintzen and diGeorge
- if these phenocopies are exposed to isotretinoin (Accutain), and Vit A analogue, then TOF is more likely
- itll stimulate the migration of neural crest cells in the region of the developing branchial crest and arches
Vit A is a morphogen, that _______
stimulates the development of a structure
- Vit A is a morphogen, that stimulates the development of a structure, so itll stimulate the migration of neural crest cells in the region of the developing branchial crest and arches
Three genes in ch 22q11 that have been ID whose haploinsufficiency causes dysfxn of neural crest cells and anterior heart fields
TBX1
CRKL
ERK2
Fetal alcohol syndrome (pg 561)
- Growth retardation
- Dysmorphic (microcephaly, facial, holoprosencephaly)
- Features and cognitive deficiencies
- Limb dislocation
- Heart defects (heart-lung fistula)
- dosage is very imp
- mechanism is failure of cell migration
Maternal folic acid deficiency increases risks for _____
spina bifida
Systems biology
studies cellular intxn and differentiation over time
Organogenesis involves heirarchies of _____
gene expression
