Birth Defects Flashcards
What is synpolydactyly?
extra digits that are fused with other digits
What are two types of txn factors?
specific and unspecific
The HOX family of genes is important for what?
patterning along the anterior-posterior border
What are the late HOX genes, 11 to 13, involved in?
development of the distal pole of the limbs
What is a morphogen?
substance secreted by cells in one part of the embryo
Where is Shh secreted from?
notochord and floor plate of neural tube
A defect in Shh secretion leads to what?
midline defects
What developmental protein must interact with cholesterol to function?
Shh
What disease features an impairment of Shh function due to a defect in cholesterol biosynthesis?
Smith-Lemli-Opitz Syndrome
What two genes are involved in detecting fluid flow in the developing kidney?
polycystin 1 and polycystin2
What do defects in polycystin 1 and 2 cause? What disease develops?
patient to not polarize cells and cysts to develop
polycystic kidney disease types 1 and 2
Where does development of the CNS begin from?
neural tube
What gene interferes with migration of neural cells?
LIS1
What condition results from defects in the LIS1 gene?
lissencephaly
What is true hermaphroditism?
patient has both testes and ovarian tissue
What is pseudohermaphroditism?
pts have either testes or ovarian tissue but the phenotype does not represent the sex
Where is the testes determining factor located?
SDR of the Y chromosome (SRY)
What happes if SRY is deleted on the Y chromosome?
female with XY karyotype
What happes if SRY is translocated to the X-chromosome?
the embryo develops into a male with an XX karyotype
What are female pseudohermaphrodites?
normal ovaries but ambiguous or male genitalia
What is the most common cause for female pseudohermaphroditism?
congenital adrenal hyperplasia
CAH often involves a defect in what enzyme?
21-hydroxylase
What does a defect in 21-hydroxylase result in?
block in cortisol synthesis with intermediates being shunted into androgen synthesis pathways
Where/when do specific txn factors function?
specific cells at specific times
HOX 11-13 are involved in what?
development of the distal pole of the limbs
Where is Shh secreted from?
notochord and floor plate (of developing neural tube)
Where does Shh diffuse to?
ventral side of body
Where does Shh influence cell development?
brain and spinal cord
A defective Shh leads to inability to develop what two structures?
midface and forebrain
Other than the notochord and floor plate, where else is Shh secreted from?
developing limb
At the developing limb, what does Shh secretion induce?
posterior limb elements
What compound must Shh interact with to function properly?
cholesterol
How does Smith-Lemli-Opitz affect Shh signaling?
it is a cholesterol biosynthesis condition
Defects in polycystin 1 or 2 impede a cells ability to sense what?
fluid flow
How do epithelial kidney tubules become polarized?
sensing fluid flow
A genetic defect in polycystin 1 or polycystin 2 results in what disease?
polycystic kidney disease
Where does development of the CNS occur?
neural tube
What gene is involved in the orderly migration of cerebral cortex cells?
LIS1
What five tissues require apoptosis for their development?
heart, digits, anus, uterus/vagina, immune system
What is true hermaphroditism?
patient has both testes and ovarian tissue
What is pseudohermaphroditism?
patient has testes or ovaries but their phenotype does not match their genetic makeup
What part of the Y chromosome drives male development?
Sex-determining region of Y (SRY)
Within the SRY, what gene determines male development?
Testes Determining Factor (TDF)
What happens if the SRY is deleted?
embryo develops in an XY female
What happens if SRY is translocated onto the X chromosome?
XX, male
Female pseudohermaphrodites possess what?
normal ovaries but ambiguous or male genitalia
What is the most common cause for female pseudohermaphroditism?
congenital adrenal hyperplasia
Congenital adrenal hyperplasia is caused by what defective enzyme?
21-beta-hydroxylase
The production of what product involves 21-hydroxylase?
cortisol
With a block in synthesis, where do cortisol substituents get shunted to?
production of androgens
The development of male sex characteristics are driven by what?
androgens
What enzyme can be implicated in the lack of development of male sex characteristics?
5-alpha-reductase
What is androgen insensitivity syndrome?
deficiency in androgen receptor production
What does the tumor progenitor model predict?
epigenetic programming errors lay the seed for cancer later in life
What do high concentrations of Shh induce? Low concentration?
high = floor plate
low = motor neurons
A defect in CREB results in what disease?
Rubinstein Taybi
Renal tubules polarize by moving what receptor?
EGFR
Where does development of the CNS begin from?
neural tube
Neuronal precursor cells begin their migration from where? What do they use as a scaffold for migration?
ventricles
glial cells
Where is the testis determining factor located?
SRY
What is the most common cause for female pseudohermaphroditism?
congenital adrenal hyperplasia
What enzyme is often absent in male pseudohermaphroditism?
5-alpha reductase
Why does a deficiency in 5-alpha reductase cause male pseudohermaphroditism?
lack of androgen production
