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
