20.05.04 Zygosity and vanishing twins

Question 1

What is zygosity?

Answer 1

• The degree of similarity of the alleles for a trait in an organism
• Specific genetic loci (HET, HEMI, HOM) or to describe twins

Question 2

Twins

Answer 2

1) Dizygotic (fraternal)
- Develop from 2 eggs fertilised from 2 sperm
- Maternal in origin (due to multiple follicle growth and ovulation rate)
- Link to TGF9 gene (insertions and deletions)
- Affected by maternal age (older = increased rate)
2) Monozygotic
- Develop from the same egg (which splits)
- 33% are DC/DA - division occurs during or before the morula stage (day 4) and separate placentas form
- 66% are MC/DA - division occurs at blastocyst stage (involves division on ICM) so get single placenta
- can also get MC/MA - where you get separation before development of embryonic axis so only one placenta and amnion form
- not 100% identical due to epigenetic and prenatal environmental post-zygotic events (such as skewed X inactivation, imprinting, unequal allocation of blastomeres to MZ ICMs)

Question 3

Problems associated with twins

Answer 3

1) 6 fold increased risk of perinatal mortality (preterm delivery, IUGR, congenital abnormalities)
- MZ have a poorer outcome than DZ twins
- Important to work out type of twins, as monochorionic placentations have more complications (MC/MA normally due to cord entanglement in separate twins)
- MC/DA have increased risk due to vascular connections between one placenta and each fetus
- IUD of one MC twin can cause renal and cerebral damage to surviving twin (?due to rapid movement of blood from deceased twin to alive twin causing severe fetal anaemia)

Question 4

Twin reversed arterial perfusion (TRAP)

Answer 4

• Rare condition of MC twin pregnancies
• Arises when the cardiac system of one twin does the work of supplying blood for both twins
• The twin supplying the blood (poorly oxygenated) is known as the “pump twin” and has a poor prognosis (50% survival), death usually occuring due to cardiac overload
• The other twin — known as the “acardiac twin” — lacks a heart or has one that is not fully formed
• It usually has a poorly developed body and may also be missing a head, limbs and torso

Question 5

Twin to twin transfusion syndrome (TTTS)

Answer 5

• Affects 4-35% of MC/DA pregnancies, early n 2nd trimester
• Occurs due to placental vascular connections between artery of one twin and vein of the other
• Get unidirectional blood flow from donor to recipient - causes asymmetrical fetal growth and fetal mortality in 80% of untreated cases
• Also get oligohydramnios in donor, and polyhydramnios and enlarged bladder in recipient
• Extremely high death rate, normally due to preterm labour induced by severe polyhydramnios

Question 6

How do they treat TTTS?

Answer 6

1) Amnioreduction - remove AF from around recipient twin to reduce pressure of fluid, but can cause preterm labour
2) Fetoscopic laser ablation - to remove placental anastomoses (connections)

Question 7

Vanishing twin

Answer 7

• Early IUD of one twin can cause VT or fetus papyraceaus (FP)
• VT - hard to detect but may be present in some degenerate villi
• FP - dead fetus persists
• Both can cause odd NIPT and CVS results
• For NIPT - demised twins cffDNA can persist for 8 weeks
• Could explain why some ‘male’ pregnancies turn out to be female (SRY detected from vanishing twin)

Question 8

Zygosity testing

Answer 8

• Degree of identity in the genome of twins
• Often requested when one twin has a phenotype that may be genetic - If MZ then higher risk of other twin also becoming affected
• Also used for transplantations where HLA identical siblings are required
• Can use polymorphic microsatellite markers to determine zygosity
• The likelihood of MZ is then calculated using Bayes theorem
• Prior risks are 3/10 MZ and 7/10 DZ (sex unknown)
• Prior risks are 4/10 MZ and 6/10 (if both are same sex)