Abnormalities of human development

Question 1

How do identical twins / triplets form ?

Answer 1

one conceptus forms 2 / 3 inner cells masses –> to form 2 / 3 genetically identical individuals

Question 2

How does chimerism occur?

Answer 2

2 genetically distinct conceptuses combine to form one individual
- fused multiple zygotes

(basically 2 twins that have fused)

Question 3

why do conjoined twins develop?

Answer 3

Incomplete inner cell mass separation

• some structures are duplicated, whilst other are not duplicated

Question 4

What is meant by mosaicism?

Answer 4

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)

Question 5

Eye color is determined by =

differentiation of eye begins about day =
–> so event must predate day 22

Answer 5

Eye color is determined by = human chromosome 15

differentiation of eye begins about day = 22
–> so event must predate day 22

Question 6

NOTE: the more X chromosomes –> the more severe the problem is for those with klinefeltner syndrome

Answer 6

-

Question 7

Down’s syndrome affects chromosome =
Edward’s syndrome affects chromosome =
Patau’s syndrome affects chromosome =

Answer 7

Down’s syndrome affects chromosome = 21
Edward’s syndrome affects chromosome = 18
Patau’s syndrome affects chromosome = 13

Question 8

mosaic OR partial extra chromosomal material = less severe symptoms than complete trisomies

Answer 8

-

Question 9

NOTE: translocation can leads to development of tumors, lymphoma, leukemia, sarcoma etc.

Answer 9

-

Question 10

What is the Holt- Oram syndrome?

What causes it?

Answer 10

• 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

Question 11

What happens in achondroplasia?

Answer 11

• 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

Question 12

What are teratogens?

Answer 12

Any agent that can disturb the development of an embryo or fetus

Question 13

what are the 3 types of teratogens

give examples in each category

Answer 13

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

Question 14

how would polydactyly occur?

Answer 14

-

Question 15

describe the development of the limbs

Answer 15

• 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

Question 16

explain how the zone of polarizing activity patterns the A/P axis

Answer 16

mirror imaged the pattern’s digits

–>

Question 17

what is the importance of sonic headgehog (shh) in the development of the limbs?

Answer 17

-Sonic Hedgehog (shh) is the polarizing factor for limb development

Question 18

How does cleft lip + palate form?

Answer 18

• 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

Question 19

what are the different forms of spina bifida?

Answer 19

1. Spina Bifida Occulta
   - Spina bifida occulta is a malformation of one or more vertebrae
2. Meningocele
   - lesion = filled with CSF
   - spine is normal
   - but there is gap in the spinal column
3. myelomeningocele
   - lesion = has connections with the spinal cord
   - spine is abnormal

Question 20

How does spina bifida occur?

Answer 20

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

Question 21

How does Anencephaly occur ?

Answer 21

similar cause to spina bifida
- anterior neuropore closure = incomplete

• folic acid supplementation - may show benefit

Question 22

What is the effect of taking the drug thalidomide ?

is it used clinically now?

Answer 22

• 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

Question 23

why do babies born early have respiratory distress syndrome? (RDS)

others = respiratory distress syndrome of newborn (RDSN), surfactant deficiency disorder (SDD);

Answer 23

• 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