Birth Defects Flashcards
(27 cards)
What are birth defects, and what is another word for birth defects?
What are birth defects caused by?
Congenital abnormalities = malformations which occur during embryonic development and are present at birth (congenital)
Genetic factors, environmental factors (e.g. radiation, drugs), or a mix of both
What is foetal alcohol syndrome, and what are the 5 main symptoms?
Growth, mental and physical problems of a baby caused when a mother drinks alcohol during pregnancy
Symptoms:
- Atypical appearance of the face (eyes, jaws, lips)
- Poor growth prenatally and after birth
- Decreased muscle tone and poor coordination
- Problems in cognitive skills
- Heart defects
What is cyclopia?
What is proboscis?
What is holoprosencephaly (Cyclopia is a form of this)?
What is Diprosopia?
Cyclopia = Rare congenital disorder characterised by the formation of a single, centrally located eye
Proboscis = When the nose is located on top of the single eye in cyclopia
Holoprosencephaly = When the cerebral cortex doesn’t split into 2 hemispheres, but remains as a single unit instead
Diprosopia = Duplication of face structures (opposite of cyclopia)
What causes cyclopia and what is the Shh signalling pathway?
What does cyclopamine do?
Mutations in Shh or blocking of Shh signalling causes cyclopia
Shh is a signalling molecule which activates the intracellular cascade:
- Patched (Ptc) = the receptor for Shh (where Shh binds), and negatively regulates smoothened
- Smoothened (Smo) = regulates the activity of the Gli complex
- Gli transcription factors regulate gene expression
Cyclopamine inhibits the activity of smoothened which will cause cyclopia
How does cyclopia cause a single eye?
Shh splits the single eye field into 2 halves during embryonic development
In the absence of Shh or Shh signalling a single eye field remains
What are medulloblastomas and what causes them? What is the treatment for medulloblastomas?
Most common malignant (severe) brain tumour in children, originating from the cerebellum
Can be caused by abnormal Shh signalling (overexpression) - mutations in the Shh pathway genes e.g. patched - Causes medulloblastomas as Shh controls the proliferation of cells in the cerebral cortex
Treatment = Inhibit (use antagonists) the abnormal Shh signalling (preventing overactivation of ptc or smo prevents overactivation of gene expression, and therefore prevents excess growth)
What is another type of cancer which is caused by abnormal Shh signalling? (not medulloblastomas)
Basal cell carcinomas
Where do limbs develop from, what is the AER, and what does it secrete?
Develop from the limb bud
AER = thickened ridge of the outer layer of the limb bud. Controls the proximal-distal axis (how long the limb is going to be).
Secretes several members of the Fgf (fibroblast growth factor) family.
What does the loss of forelimb AER, late AER, and central gap in the AER all cause? (3 separate things)
- Loss of forelimb AER = loss of arms
- Loss of late AER = Acheiropodia = loss of distal extremities (lower arms and legs)
- Central gap in the AER = Ectrodactyly = split hand/foot malformation (gaps in the hand and feet)
How can fibroblast growth factors help in AER function, when AER is non-functioning?
FGFs can substitute for AER function - e.g. AER replaced by a FGF bead restores normal limb growth
What is phocomelia and what is it caused by?
Birth defect resulting in very short limbs
Can be a result of a disturbed interaction between the AER and the limb bud
What is the ZPA and how does it work?
Specifies the anterior-posterior limb axis (how wide the limb is)
Works by producing Shh, which is required for full limb development
What can a mutation in the Shh gene lead to, in terms of ZPA activity? (3 things)
Development of only one digit (finger) instead of 5
OR
Polydactyly - developing more than 5 fingers
Mirror image polydactyly - mirror imaging of some fingers
How are digits (fingers) formed, and what is syndactyly?
Programmed cell death of the interdigit regions
Syndactyly = where 2 or more digits are fused together - caused by failure of apoptosis
What are Hox genes , and what do mutations in Hox genes cause?
5 prime end of Hox genes specify regions of the forelimbs (upper body) and the 3 prime end specifies regions of the hind limbs (lower body)
Mutations cause homeotic transformations = one body part being transformed into another
what are the 2 steps in sex determination and what does each involved? (include when the Mullerian and wolffian ducts degenerate/stay)
Primary sex determination = formation of either ovary or testis from the bipotential gonad, controlled by the sex chromosomes (X and Y):
- In ovarian development, the wolffian duct degenerates and the Mullerian duct stays
- In testis development, the Mullerian duct degenerates and the wolffian duct stays
Secondary sex determination = development of male and female characteristics, usually by hormones secreted from the gonads (testosterone and oestrogen). Has 2 major phases - during organogenesis (when the organs are developing in the embryo) and at puberty
What is Klinefelter-syndrome, and what is Turner syndrome, and what does each of them lead to?
Klinefelter-syndrome = XXY individuals who are male, leads to under-developed testes and breast development
Turner syndrome = XO individuals who are female, leads to poor breast development and under-developed ovaries
What is the SRY gene, and what does it control?
What happens when XX individuals have a SRY gene on one of their chromosomes?
What does the Wnt4 gene potentially determine?
The sex determining region on the Y chromosome, drives the formation of testis
XX individuals with SRY gene can induce the formation of male genitals and characteristics (male without a Y chromosome)
Wnt4 is a potential ovary determining gene
Which female and male hormones control secondary sex determination (one for females, 2 for males) and what do they do?
Female characteristics controlled by oestrogen, which also enables the development of the Mullerian duct
Male characteristics determined by:
- Anti-Mullerian Hormone (AMH), which enables the degeneration of the Mullerian duct
- Testosterone, which differentiates the wolffian duct into parts of the testis, as well as controlling the development of the scrotum and penis
What type of signalling is sex hormone signalling (hydrophobic or hydrophilic), and what do defects in this signalling lead to?
Sex hormones are steroid hormones, so have steroid hormone signalling (hydrophobic, can cross the membrane)
Binds to receptor in the cytoplasm to for a hormone receptor complex (HRC), which travels to the nucleus and binds to DNA to alter gene expression
Defects in this signalling leads to defects in secondary sex characteristics
What is an intersex condition?
What is an example of an intersex condition and what is seen in individuals who have it?
Condition where both male and female traits are seen in the same individual
Androgen insensitivity syndrome - patients are XY with an SRY gene. Have testes that make testosterone and AMH, but lack testosterone receptor so can’t respond to the testosterone made by their testes. Patients have oestrogen receptors and so respond to the oestrogen produced in the adrenal glands and develop female characteristics (are genetically male, but have female characteristics)
What is pseudohermaphrotism, and how is it caused in males and how is it caused in females?
Pseudohermaphrotism = Individual has one type of gonad, but the secondary characteristics are different from the gonadal sex
In males: Have testes (male gonads), but female secondary characteristics (breasts)
Caused by mutations in the testosterone receptor or mutations affecting testosterone synthesis (either can’t produce testosterone, or can’t react to it)
In females: Have ovary, but male secondary characteristics (e.g. beard, deep voice)
Caused by congenital adrenal hyperplasia - genetic deficiency of an enzyme that metabolises cortisol, leading to production of male hormones
What is a “true” hermaphrodite?
Individuals which contain both male and female gonadal tissue (have both ovaries and testes)
What happens to one of the X chromosomes, to prevent overexpression of genes in females?
How does this lead to “true” hermaphrodites?
One of the X chromosomes is inactivated at random in each cell to prevent overexpression of X chromosome genes.
In “true” hermaphrodites, the recombined SRY gene can land on the X chromosome instead of the Y chromosome. this can cause development of both female and male gonads. (If all cells are XX, SRY gene will land on the active X in some cells (causing male tissue development) and the inactive X in other cells (causing female tissue development, as it is inactive, it won’t affect anything)
