6. Development Flashcards
What is a cleft palate?
- Connection between the mouth and the nasal cavity
- 2 components haven’t fused at the centre to form the hard palate
- Causes problems with breathing, eating and drinking
Is foetal mal-development more likely to be genetic or environmental?
Genetic (but even more likely to be multifactorial)
What infectious agents can cause mal-development?
- Rubella e.g. cataracts
- HSV e.g. microcephaly
- HIV e.g. microcephaly
- Syphilis e.g. mental retardation
- Zika e.g. microcephaly
What physical agents can cause mal-development?
X-rays and other ionising radiation e.g. microcephaly, cleft palate etc.
What chemical agents can cause mal-development?
- Thalidomide e.g. limb defects
- Lithium e.g. heart malformation
- Amphetamines e.g. cleft lip
- Cocaine e.g. growth restriction
- Alcohol e.g. foetal alcohol syndrom
When is the CNS vulnerable to teratogens?
Whole of development
Do teratogens impact development in the first couple of weeks?
No, but the foetus would just be miscarried (not a teratogenic effect)
What is chimerism?
2 genetically distinct conceptuses combine to form one individual - no issues
What is mosaicism?
Differences in genetic makeup between cells within one individual
What are the effects of the following chromosome abnormalities: • Klienfelter's syndrome (XXY) • XYY • XXX • XXXX
- Klienfelter’s syndrome (XXY) - decreased fertility
- XYY - variable (taller, learning problems)
- XXX - limited effects, some mental changes
- XXXX - severe effects
What problem determines survival in Down’s syndrome (Ch21)?
Heart problems
What is prognosis like for foetuses with Edward’s (Ch18) and Patau’s (Ch13) syndrome (both trisomy)?
Most die before birth
Has Ch1 trisomy ever been found in pregnancy loss tissues?
No
What is Turner’s syndrome?
- XY linked - X0 (lost chromosome)
- Female, short stature, infertile
- Y0 is not viable as boys need the X chromosome
Are there any autosomal syndromes involving the loss of a chromosome?
No, but partial chromosome loss syndromes are known
Give an example of a genetic condition seen in animals and humans
Piebaldism
• Mild mutation of the KIT receptor
• Mouse can have pale patch of fur
• Human can have pale streak on forehead
What is Holt-Oram syndrome?
Due to mutation in TBX5 (TF) - required as both structures develop
- Structure of the heart and division between the chambers doesn’t develop properly
- Heart becomes bigger
- Lack of symmetry in the left and right hand
- Thumb can become a finger
What is Achondroplasia?
Gain of function mutation in FGFR3
- Conversion of cartilage to bone
- Lack of bone growth in long bones
- Achondroplastic dwarfism
What is Polydactly?
- Extra digit
- Duplication of digital rays (have 6 not 5)
- Webbing may stay put - extra digit has formed too close
When do the limbs form in a foetus?
- Forelimb bud - day 27/28
- Hindlimb bud - day 29
- Grows from the lateral plate mesoderm
- Digits are fully formed and patterned by day 56
What are the 2 types of gaps in a cleft lip?
Unilater or bilateral (has bigger gap)
In how many places can there be a cleft palate?
1 - midline
Does the cleft palate and lip need to be mended?
- Cleft palate must be mended to prevent food from entering the nasal cavity and lungs
- Cleft lip repair is important for cosmetic and psychological reasons
How well does a mended cleft palate/lip repair?
Well as cells in babies proliferate quickly with little scarring
What are the 3 forms of spina bifida?
- Hidden form (CNS is ok, but spine hasn’t formed correctly) - spina bifida occulta
- CSF filled swelling - meningocele
- Swelling with nervous tissue - myelomeningocele
Can surgery help spina bifida?
- Can help anatomical problems
* Can’t solve the functional problem
When does spina bifida development take place?
Within the first 4 weeks (PF)
How is spina bifida related to neurulation?
- Transformation of neural plate into neural tube
- Tube does not completely seal up in spina bifida
- Due to bulge in CNS which stops complete formation
- Forms posterior neuropore
Which nutrient is important to prevent spina bifida and anencephaly
Folic acid
(should be given 3 months prior to conception, as the egg does most of it’s development before selection as the main follicle)
What causes anencephaly?
Incomplete anterior neuropore closure
When does anencephaly develop?
Around 23 days (PF)
What is thalidomide and it’s significance in pregnancy?
- Was used to treat Hyperemesis gravidarum in pregnancy
- Found out to affect foetus limbs (mainly upper)
- Also caused deformed eyes, deformed hearts, deformed alimentary and urinary tracts, blindness and deafness
- 50% initial survival rate
- Now used in some leprosy and cancer treatments
- Cannot be given to women of reproductive age
What polarising factor for limb development?
Sonic Hedgehog (shh)
How does thalidomide cause limb defects?
- One of the isoforms stops blood vessel development
- Cell death results
- Limbs are devoid of nutrients and truncates prematurely
How does exposure time to thalidomide effect limb loss?
- Short exposure - partial limb loss (Phocomelia)
* Longer exposure - complete limb loss (Amelia)
What is respiratory distress syndrome (RDS)?
- If a baby is born early, the lungs might not be developed enough
- Lack of surfactant so surface tension can’t be reduced enough
- Causes difficulty in breathing
When does surfactant production begin?
26 weeks (post-fertilisation) = 24 weeks gestational age
When is there enough surfactant in the lungs to be able to breath normally?
Only at term
How can in utero production of surfactant be increased?
1 injection of glucocorticoids 2-3 days before delivery
What is the chance of having respiratory distress syndrome if the baby is born at 24 weeks?
100%
