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SP17 Suspected confined blood chimerism in monochorionic dizygotic (MCDZ) twins or Twin-Twin confusion syndrome. David Gokhale Molecular Genetics Laboratory Liverpool Women’s Hospital. Summary. Brief reminder about twinning etc. Reproductive and Obstetric history Neonatal History - PowerPoint PPT Presentation
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SP17
Suspected confined blood chimerism in monochorionicdizygotic (MCDZ) twins
or
Twin-Twin confusion syndrome
David GokhaleMolecular Genetics Laboratory
Liverpool Women’s Hospital
Summary
• Brief reminder about twinning etc.
• Reproductive and Obstetric history
• Neonatal History
• Molecular and cytogenetic analysis
• Conclusions and discussion
From Hall, J.G., Twinning, Lancet 2003; 362: 735–43
Definitions
• Mosaicism
The presence in an individual or tissue of at least two cell lines differing in genotype or karyotype, but derived from one zygote.
• Chimerism
The presence of cells from two genetically distinct sources (e.g. transplant, graft or embryo fusion).
From Hall, J.G., Twinning, Lancet 2003; 362: 735–43
Reproductive and Obstetric history
• Conceived by IVF
• Antenatal ultrasound (USS) at a local district general hospital showed a twin pregnancy and a monochorionic, diamniotic placenta
• Antenatal steroids given following premature rupture of membranes on twin 2 noted at 24+2 weeks gestation.
Delivery
• Twins delivered by emergency c-section at 25+1 weeks gestation– Twin 1: Phenotypically Male, 710 grams– Twin 2: Phenotypically Female, 740 grams
• Both twins required resuscitation, intubation and surfactant before being transferred to the Neonatal Unit at LWH.
Neonatal History – Twin 1 (male)
• Better condition at birth
• Respiratory difficulties
– ventilated for 39 days in total– chronic lung disease
• many “near death” experiences
HR = 60
SaO2 = 40
Time = 10 mins
• Transfusions x9
• Laser treatment for retinopathy of prematurity carried out 6th August
• Home day = 142, term + 5 weeks
Neonatal History – Twin 1 (male)
• Poorer condition at birth
• better respiratory outcome– 36 days ventilation– chronic lung disease – weaned off oxygen before discharge
• less “near death” experiences
Neonatal History – Twin 2 (female)
• Transfusions x8
• Laser treatment for retinopathy of prematurity carried out 6th August
• Home day 118, term + 1 week
Neonatal History – Twin 1 (female)
Referral
• Discrepancy between USS findings and twin’s gender raised by the parents approx 4 weeks later
• Placental histology confirmed monochorionic diamniotic placenta
• Samples then taken for genetic analysis
X and Y chromosome microsatellite analysis
Male Twin
Female Twin
Analysis of initial blood samples
DYS448DXS6803 DXS981
DYS448DXS6803 DXS981
Subsequent Investigations
• Buccal swabs taken from both twins
• Female twin (twin 2)– abdominal USS showed normal uterus– endocrine and thyroid investigations normal– thyroid function normal
• Male twin (twin 1)– endocrine & thyroid investigations normal– hernia repair scheduled with tissue sampling (risk of
gonadoblastoma)
Analysis of buccal cell samples
Male Twin
Female Twin
DYS448DXS6803 DXS981
DYS448DXS6803 DXS981
Male Twin – Analysis of hernial sac & inguinal skin
Uncultured
Cultured
DYS448
DYS448
DXS6803
DXS6803 DXS981
DXS981
Cytogenetic analysis
• No cells detected in any tissues with XXY
• Blood sample FISH analysis (DXZ1 & SRY): – Male twin (95% XX, 5% XY)– Female twin (88% XX, 12% XY)
• Analysis of cultured cells from hernial sac and inguinal skin only detected presence of XY cells in male twin
Conclusions
• Our findings are suggestive of chimerism limited to blood
• Possible mechanisms (Williams et al. 2004)– Placental vascular anastomoses (after the development of
haematoblast stem cell lines) or– Admixture of trophoblast cells during early blastocyst development
(restricted to the extra-embryonic tissues)
• Only been 10 case reports (the earliest being 1977) of blood chimerism in dizygotic twins of opposite genders
Discussion
• Up to 8% of dizygotic twins have been noted to have some evidence of blood chimerism (van Dijk, et al.)
• Has IVF increased the likelihood of embryo fusion due to proximity ?
• Is the apparent chimerism likely to persist and for how long?
Acknowledgements
• Julie Sibbring (Molecular Genetics, LWH)• Frances White (Molecular Genetics, LWH) • Aram Buchanan (Cytogenetics, LWH)• Magda Ainscough (Cytogenetics, LWH)• Dan Hawcutt (SpR & Lecturer in Paediatric Pharmacology,
LWH)• Leanne Bricker (Consultant Obstetrician, LWH)• Family ‘G’