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David Gokhale Molecular Genetics Laboratory Liverpool Women’s Hospital

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

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David Gokhale Molecular Genetics Laboratory Liverpool Women’s Hospital

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  1. SP17Suspected confined blood chimerism in monochorionicdizygotic (MCDZ) twinsorTwin-Twin confusion syndrome David Gokhale Molecular Genetics Laboratory Liverpool Women’s Hospital

  2. Summary • Brief reminder about twinning etc. • Reproductive and Obstetric history • Neonatal History • Molecular and cytogenetic analysis • Conclusions and discussion

  3. From Hall, J.G., Twinning, Lancet 2003; 362: 735–43

  4. 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

  5. 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.

  6. 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.

  7. Neonatal History – Twin 1 (male) • Better condition at birth • Respiratory difficulties • ventilated for 39 days in total • chronic lung disease • many “near death” experiences

  8. HR = 60 SaO2 = 40 Time = 10 mins

  9. Neonatal History – Twin 1 (male) Transfusions x9 Laser treatment for retinopathy of prematurity carried out 6th August Home day = 142, term + 5 weeks

  10. Neonatal History – Twin 2 (female) • Poorer condition at birth • better respiratory outcome • 36 days ventilation • chronic lung disease • weaned off oxygen before discharge • less “near death” experiences

  11. Neonatal History – Twin 1 (female) Transfusions x8 Laser treatment for retinopathy of prematurity carried out 6th August Home day 118, term + 1 week

  12. 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

  13. X and Y chromosome microsatellite analysis

  14. Analysis of initial blood samples Male Twin DXS6803 DXS981 DYS448 Female Twin DXS6803 DXS981 DYS448

  15. 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)

  16. Analysis of buccal cell samples Male Twin DXS6803 DXS981 DYS448 Female Twin DXS6803 DXS981 DYS448

  17. Male Twin – Analysis of hernial sac & inguinal skin Uncultured DXS6803 DXS981 DYS448 Cultured DXS6803 DXS981 DYS448

  18. 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

  19. 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

  20. 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?

  21. 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’

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