Embryology- complications of development Flashcards
Define teratology.
Structure of a tissue has not developed appropriately. Can define what has gone wrong- what is the likely cause, know what the mother was exposed to, can look at what has happened and deduce where it went wrong.
Define birth defect/ congenital malformation/ congenital abnormality.
Something has gone wrong during the developmental process.
Define dysmorphology.
Altered basic shape of a tissue or structure. Equivalent to teratology.
What proportion of pregnancies are affected by major abnormalities?
About 3%.
What proportion of infant deaths are caused by major developmental abnormalities?
25%.
What proportion of pregnancies are affected by minor abnormalities?
About 15%.
What are the major causes of developmental abnormalities in pregnancy?
Genetic- 30%.
Environmental- 15%.
Multifactorial- 55%.
Define teratogen.
Any agent that can disturb the development of an embryo or foetus.
What infectious agents can cause developmental abnormalities in pregnancy?
Rubella virus: cataracts, glaucoma, heart defects, deafness, teeth
Herpes simplex virus: microphthalmia, microcephaly, retinal dysplasia
HIV: microcephaly, growth restriction
Syphilis: mental retardation, deafness
Zika virus: microcephaly
What physical agents can cause developmental abnormalities in pregnancy?
X-rays and other ionising radiation: microcephaly, spina bifida, cleft palate, limb defect.
What chemical agents can cause developmental abnormalities in pregnancy?
Thalidomide: limb defects, heart malformations
Lithium: heart malformations
Amphetamines: cleft lip and palate, heart defects
Cocaine: growth restriction, microcephaly, behavioural abnormalities
Alcohol: foetal alcohol syndrome, maxillary hypoplasia, heart defects
What are the broad categories of external causes of developmental abnormalities in pregnancy?
Teratogens
Infectious agents
Physical agents
Chemical agents
How can differences in chromosome distribution cause developmental abnormalities?
Mosaicism (nondisjunction)- differences between cells within one individual.
Distribution of cells between inner cell mass and trophectoderm (placenta).
Chimerism- fused multiple zygotes (non-identical zygotes).
Give an example of a developmental abnormality resulting from too many chromosomes, XY linked.
Kleinfelter’s syndrome (XXY)- decreased fertility.
XXYY, XXXY, XXXYY, etc.- severe forms related to KS.
XYY (XYYY)- very variable (taller, learning problems).
XXX- limited effects, some mental changes.
XXXX, XXXXX- more severe effects.
Give examples of developmental abnormalities resulting from too many chromosomes, autosomal.
Down’s syndrome (ch21):
- 1/1000 live births
- heart problems determine survival
Edward’s syndrome (ch18):
- 1/6000 live births
- most die before birth, very few live-born, live <2 weeks.
Patau’s syndrome (ch13):
- 1/15,000 live births
- most die before birth, 80% live-born die within 1 year
Others not found in live birth, most detected in some spontaneous pregnancy loss tissues.
Ch1 trisomy not found in pregnancy loss tissues.
Give an example of a developmental abnormality resulting from too few chromosomes, XY linked.
Turner’s syndrome- X0:
- female, short stature, infertile
- Y0 not viable.
What results from a developmental abnormality resulting from too few chromosomes, autosomal.
No complete losses are viable.
Partial chromosome loss syndromes known and characterised/
Give an example of a developmental abnormality resulting from altered distribution of chromosomes, XY linked.
‘XX male’- XY translocation.
Give an example of a developmental abnormality resulting from altered distribution of chromosomes, autosomal.
Linked with development of tumours, lymphoma, leukaemia, sarcoma.
What is Holt-Oram syndrome?
Atrial septation defects
Range of hand abnormalities
Phenotype due to mutation in TBX5 (transcription factor)- required as both structures develop
What is achondroplasia?
Gain of function mutation in FGFR3.
Achondroplasia means ‘lack of cartilage’.
Defect is in conversion of cartilage to bone and lack of bone growth.
Describe the process of limb development in utero, with timings.
Forelimb bud appear at d27/8.
Hindlimb bud at d29.
Grow out from lateral plate mesoderm rapidly under control of special signalling regions.
Fully formed and patterned by d56.
What are 3 forms of spina bifida?
Spina bifida occulta (hidden, hairy)
Meningocele
Myelomeningocele
What is the incidence of spina bifida?
1-2 per 1000 pregnancies.
What are the benefits of surgery for spina bifida?
Can help anatomically but not with functional neurological problems.
How and when does spina bifida occur?
Development of bony part of spine is driven by neural tissue.
No bone forms over the region.
Faulty neurulation (posterior neuropore).
Occurs in the first 4 weeks after fertilisation.
How does folic acid in diet influence spina bifida?
Decreases incidence by around 70%. Should be given 3 months before conception.
What is anencephaly and its incidence?
‘Headless’- top part of the head doesn’t develop properly, ‘top end’ spina bifida.
Anterior neuropore closure incomplete.
Incidence: 1-8 per 10,000 births.
Female babies affected more commonly than male.
Occurs about 23 days post-fertilisation.
What are the effects of thalidomide on pregnancy and foetal development?
~10,000 affected infants known, ~50% initial survival rate.
Limbs affected- effects on upper limbs most common, but lower limbs and internal organs can also be affected.
In addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness.
Used in some leprosy and cancer treatments at present.
Affects rapidly developing blood vessels, notably those of upper limbs.
Blood vessel effects can be generic, hence the range of effects observed.
What is the polarising factor for limb development?
Sonic hedgehog (shh).
