Abnormalities of development Flashcards
Whats is Thalidomide?
- A drug originally used for the treatment of morning sickness
- Found to cause many fetal abnormalities
- Now used for the treatment of some cancers and some complications of leprosy
How does Thalidomide work?
- Seems that it damages developing blood vessels, thus depriving the adjacent cells of nutrients and preventing their proper growth and development
- It was administered when morning sickness was worst (8 weeks GA onwards) which is a particularly sensitive time for limb development
- Effects the upper limb vessels very strongly
What abnormalities may occur during renal development?
- One kidney may be retained in the pelvis, rather than moving to the usual abdominal position
- Retention of an extra artery (or another problem) may obstruct (partly or fully) the ureter, and cause enlargement of the renal pelvis
- The kidneys form separately but may fuse to form a horseshoe kidney. The extra tissue makes it impossible for it to move, so it will remain in the pelvis.
- 2 kidneys are needed during development so this may effect renal function
What is the most common cause of male mal developments?
- The inability to produce the appropriate hormones (testosterone and anti-Mullerian hormone (AMH)
- The inability of target tissues to respond to these hormones, normally the result of defects in the cognate receptors.
What are the features of Androgen Insensitivity Syndrome?
- Mutant androgen receptor
- Limited virilisation of external genitalia (which show relatively normal female structures).
- The mesonephric (Woolffian) ducts are rudimentary or lacking.
- Testis structure is variable, and they do not descend.
- AMH production from Sertoli cells is relatively normal, so Mullerian (paramesonephric) ducts regress and no female structures (uterus, oviducts) are present.
What causes Congential Adrenal Hyperplasia?
- A mutation in Cytochrome P450 21-hydroxylase enzyme (CYP 21A2)
- Cortisol production from the fetal adrenal is very limited as this enzyme is key in cortisol synthesis.
- The lack of cortisol means that there is no negative feedback on pituitary ACTH output, leading to high ACTH,
- Over-stimulation of the fetal adrenals, which make weak androgens (e.g. androstenedione).
What is the result of Congential Adrenal Hyperplasia on the genitalia?
- Partial virilisation of the genitalia.
- The internal systems are female, as there is no SRY (no testicular development),
- No male ducts (no testosterone)
- Female ducts develop (no AMH, as no Sertoli cells).
What is the Tetraology of Fallot?
4 congenital abnormalities:
- Pulmonary stenosis
- Thickened right ventricle wall
- Ventricular septal defect
- Overriding aorta - allows blood from both ventricles to enter
What is a transposition of the great arteries?
The aorta and pulmonary arteries switch which artia
What is the treatment for transposition of the great arteries?
- Not noticeable until after birth
- administering prostaglandins to keep the ductus arteriosus open
- surgical intervention to switch the vessels back
What are the causes of mal-development
- Genetic – 30%
- Environmental – 15%
- Multifactorial – 55%
How do identical twins form?
one conceptus forms 2 inner cells masses to form 2 genetically identical individuals
What is chimerism?
• genetically distinct conceptuses combine to form one individual
How do conjoined twins occur?
Incomplete inner cell mass separation
What is mosaicism?
- Mitotic non-disjunction in the developing fetus
- One cell gets an extra copy of a chromosome and the other cell doesn’t get any
- Earlier it happens in development the more severe the phenotypic change.
What are the major chromosomal abnormalities?
- Autosomal loss is non-viable
- Only autosomal trisomy are trisomy 21 (downs syndrome) trisomy 18 (edwards syndrome) and trisomy 13 (patau’s syndrome)
- Extra sex chromosomes are normally viable with mild phenotypic changes
- Loss of sex chromosomes is serious XO (turners) being infertile with strong phenotypic changes and YO inviable
What is Holt-oram syndrome caused by?
Gene mutation that codes for TBX5 - a transcription factor required for the development of the heart and the thumbs
What has spinal bifida been strongly linked to a lack of?
Folate - 70% of cases
When should folate supplements be taken to avoid spinal bifida?
3 months before conception right through pregnancy
What causes achondroplasia?
Mutation in the FGFR3 gene
Cartilage isnt converted to bone
What is Polydactyly?
extra digits
What causes spinal bifida?
- Fusion should occur through the neural tube, but in spina bifida this process is not completed.
- The meningeal membranes that cover the spinal cord protrude through the opening, forming a sac enclosing the spinal elements, such as meninges, cerebrospinal fluid, and parts of the spinal cord and nerve roots
What defects can arise due to the nature of facial development?
- Cleft lip
- Usually asymmetrical
- Usually in the upper lip
- Cleft palate
* Usually symmetrical
What are the 3 types of spinal bifida?
- Occulta
* Relatively little effect, may be irregular hair growth in the area - Meningocele - gap in spine where meningies has bulged out and there is a CSF filled out-pouching
* Nerve function may be compromised - Myelomeningocele
* Spinal cord itself bulges out into the lesion
* Massive effect on the function of nerves below this level
What is Anencephaly?
•Defect in skull and brain development
What causes anencephaly?
- Anterior neuropore closure incomplete
- Linked to lack of folate
What is RDS?
Respiraotry distress syndrome
The infant has not produced sufficient surfactant
How can RDS be ‘treated’?
Give the mother a dose of glucocorticoids 24-48 hours pre-delivery
Give artificial surfactant to the baby
