6. Embryology- Complications of Development Flashcards
What is the cause of conjoined twins?
Incomplete inner cell mass separation
What causes formation of identical twins/triplets?
1 conceptus forms 2/3 inner cell masses to form 2/3 genetically identical individuals
What causes chimerism?
2 genetically distinct conceptuses combine to form 1 individual
What is mosaicism?
Non-disjunction event resulting in differences between cells within one individual
e.g. Heterochromia
Name some presentations of chimerism?
Blaschko’s lines (lines of normal cell division)
When does differentiation of eyes begin?
What is the significance?
Day 22 post fertilization
Mosaicism/ chromosomal event must predate
What is Edward’s Syndrome?
Trisomy 18
Most die before birth, fatal
Small size and heart defects
What is Patau’s Syndrome?
Trisomy 13
Most die before birth, 80% die within 1 year
Multi-organ defects
What is a common presentation of mutation of KIT receptor?
Piebaldism
What is Holt-Oram Syndrome?
Due to mutation in TBX5 (transcription factor)
Atrial septation defects
Range of hand abnormalities
What is Achondroplasia?
Gain of function mutation in FGFR3
Defect in conversion of cartilage to bone and lack of bone growth
What is the main effect of lithium on development of embryo/foetus?
Heart malformation
What is the effects of amphetamines on embryo development?
Cleft lip and palate, heart defects
What effects do physical agents like X-rays have on foetal development?
Microcephaly
Spina Bifida
Cleft palate
Limb defects
Outline limb development
D27/28: Forelimb bud
D29: Hindlimb bud, grow out from lateral plate mesoderm rapidly under control of special signalling regions (AER-HOX genes expressed)
D56: fully formed and patterned
What is the zone of polarizing activity (ZPA)?
Area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis.
Usually as posterior
High conc: bud forms at posterior
Low conc: bud forms at anterior
What is the polarizing factor for limb development?
Sonic Hedgehog (shh)
What is the pathogenesis of cleft palate?
- Occurs during Carnegie stage 18 (~6 weeks)
- Lack of fusion of palatine shelves (Involves tissue migration)
- Persistent labial groove
What is the pathogenesis of spina bifida?
Failure to complete neurulation (union of 2 halves of neural arches); which is controlled by underlying notochord (posterior neuropore)
Problem present within 4 weeks of fertilisation
What are the types of spina bifida?
Describe them.
- Occulta May be overlied by tuft of hair - Cystica (Meningocele) Only meninges protrude - Cystica (Meningomyelocele) Both meninges and CNS elements (spinal cord, cauda equina) protrude - Myelocele Neural folds remain open, allowing CSF to leak onto surrounding skin
What is the pathogenesis of Anencephaly?
- Anterior neuropore closure incomplete
- Similar causes to spina bifida (e.g. folic acid)
What are the 2 possible birth defects of Thalidomide?
- AMELIA - prolonged exposure leading to widespread cell death
- PHOCOMELIA - short exposure leading to uniform cell death and only partial loss of AER signalling
How does thalidomide cause limb defects?
Affects (upper limb) rapidly developing blood vessels
Administration for morning sickness at 6-8 weeks when limb is rapidly developing
What can the teratogen amphetamines cause?
Cleft lip and palate
Heart defects
