Abnormalities of human development Flashcards
How do identical twins / triplets form ?
one conceptus forms 2 / 3 inner cells masses –> to form 2 / 3 genetically identical individuals
How does chimerism occur?
2 genetically distinct conceptuses combine to form one individual
- fused multiple zygotes
(basically 2 twins that have fused)
why do conjoined twins develop?
Incomplete inner cell mass separation
- some structures are duplicated, whilst other are not duplicated
What is meant by mosaicism?
Mosaicism (non disjunction) – differences between cells within one individual
- normal pattern of mitosis doesn’t form
e. g one eye color is different from the other
e. g tortoiseshell cats (heterozygous females cats)
Eye color is determined by =
differentiation of eye begins about day =
–> so event must predate day 22
Eye color is determined by = human chromosome 15
differentiation of eye begins about day = 22
–> so event must predate day 22
NOTE: the more X chromosomes –> the more severe the problem is for those with klinefeltner syndrome
-
Down’s syndrome affects chromosome =
Edward’s syndrome affects chromosome =
Patau’s syndrome affects chromosome =
Down’s syndrome affects chromosome = 21
Edward’s syndrome affects chromosome = 18
Patau’s syndrome affects chromosome = 13
mosaic OR partial extra chromosomal material = less severe symptoms than complete trisomies
-
NOTE: translocation can leads to development of tumors, lymphoma, leukemia, sarcoma etc.
-
What is the Holt- Oram syndrome?
What causes it?
- defect of the heart / hand
can cause:
- atrial septation defects - (eventually leads to hypertrophy)
- hand abnormalities
- -> phenotype is due to mutation in TB X5 (transcription factor)
- which is requred for the development of both structures
What happens in achondroplasia?
- GAIN of function mutation in FGFR3
- there is a defect in the conversion of cartilage to bone
- -> and there is a lack of bone growth
What are teratogens?
Any agent that can disturb the development of an embryo or fetus
what are the 3 types of teratogens
give examples in each category
Infectious agents
- 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
Physical agents
- X-rays & other ionising radiation –> Microcephaly, spina bifida, cleft palate, limb defects
Chemical agents
- Thalidomide - Limb defects, heart malformations
- Lithium - Heart malformations
- Amphetamines - Cleft lip and palate, heart defects
- Cocaine - Growth restriction, microcephaly, behavioral abnormalities
- Alcohol - Fetal alcohol syndrome, maxillary hypoplasia, heart defects
how would polydactyly occur?
-
describe the development of the limbs
- forelimb bud appears at day 27 / 28
- hind limb develops at day 29
- they grow out from the lateral plate mesoderm rapidly
- -> under control of signaling regions
- limbs are fully formed by day 56
explain how the zone of polarizing activity patterns the A/P axis
mirror imaged the pattern’s digits
–>
what is the importance of sonic headgehog (shh) in the development of the limbs?
-Sonic Hedgehog (shh) is the polarizing factor for limb development
How does cleft lip + palate form?
- during early development , there would be 2 grooves or furrows
- normally, grooves gets filled in as the medial nasal prominence merges
- however if tether is persistent labial groove, cleft lip forms
what are the different forms of spina bifida?
- Spina Bifida Occulta
- Spina bifida occulta is a malformation of one or more vertebrae - Meningocele
- lesion = filled with CSF
- spine is normal
- but there is gap in the spinal column - myelomeningocele
- lesion = has connections with the spinal cord
- spine is abnormal
How does spina bifida occur?
fusion process starts in the middle - and progresses to head and tail direction
- -> but if there is incomplete closure of the neural tube
- -> spina bifida occurs
- problem is present within 4 weeks of fertilization
–> can occur due to folic acid deficiency
Note: give at three months
How does Anencephaly occur ?
similar cause to spina bifida
- anterior neuropore closure = incomplete
- folic acid supplementation - may show benefit
What is the effect of taking the drug thalidomide ?
is it used clinically now?
- affects rapidly developing blood vessels, notably those of upper limbs
- limbs effected
- deformed eyes + hearts
- deformed alimentary / urinary defects / blindness / deafness
- greater dose + longer time –> greater effects
is it used clinically now?
- used in some leprosy and cancer treatments at present
why do babies born early have respiratory distress syndrome? (RDS)
others = respiratory distress syndrome of newborn (RDSN), surfactant deficiency disorder (SDD);
- lung starts developing early
and goes on through whole duration of development
–> primarily due to surfactant deficiency
babies born at
at GA 24 weeks - 100% would have RDS
at GA 26-28 weeks - 50% would have RDS
at GA 30-31 weeks - 25% would have RDS
