Diagnosis and management of heterokaryotypic monochorionic twins

Lewi, Liesbeth; Blickstein, Isaac; Schoubroeck, Dominique Van; Gloning, Karl-Philipp; Casteels, Martine; Brandenburg, Helen; Deprest, Jan

doi:10.1002/ajmg.a.31052

Cited by 60 publications

(48 citation statements)

References 18 publications

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“…But such twins can only survive because they are MC, with an interchanged blood supply. Of six consecutive heterokaryotypic MC twin pairs, four involved the X chromosome and two involved autosomes [Lewi et al, 2006]. Dual amniocentesis was superior to villous sampling in prenatal diagnosis.…”

Section: Genetic/epigenetic Discordancementioning

confidence: 91%

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Machin

2009

American J of Med Genetics Pt C

138

102

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Monozygotic twins (MZ) are rarely absolutely “identical.” This review discusses the types of genetic/epigenetic and prenatal environmental post‐zygotic mechanisms that cause discordance within such twin pairs. Some of these mechanisms—ranging from heterokaryotypia to skewed X‐chromosome inactivation—may cause extreme discordance, but these extremes are merely the more emphatic examples of discordance that, to some degree, underlies the majority of MZ twin pairs. Because of the entrenched misconception that MZ twins are necessarily identical, many MZ twin pairs are mistakenly designated as dizygotic (DZ). Clinical benefits to accurate zygosity determination include correct solid organ transplantation matching, if one twin requires donation for a non‐genetically mediated disease; the opportunity of preventive management for disorders that do not manifest synchronously; and better counseling to parents regarding their individually unique, and often psychologically puzzling, twin offspring. In twin pairs with complex and confusing biological origins, more detailed zygosity testing may be required. For example, intermediate trigametic and tetragametic chimeric dizygotic twins are reviewed, some of whom are, nevertheless, monochorionic (MC). Because of inter‐fetal vascular anastomoses in MC twins, genetic results from blood samples may not accurately reflect discordance in solid organs. Previously, it was thought that MZ twinning was some sort of embryological fluke. However, familial monozygotic twinning is more common than suggested by the literature. Seven new families are presented in an accompanying paper. Despite the difficulties and dangers of twin pregnancy (especially so for MC twins), human twinning persists, and continues to both challenge and fascinate parents, clinicians and geneticists. © 2009 Wiley‐Liss, Inc.

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Section: Genetic/epigenetic Discordancementioning

confidence: 91%

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Machin

2009

American J of Med Genetics Pt C

138

102

View full text Add to dashboard Cite

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“…Nevertheless, heterokaryotypic monozygotic twinning is a rare occurrence, and most reports in the medical literature concern monochorionic twins discordant for Turner syndrome (45, X). 5,6 There are only four reports of monochorionic twins discordant for trisomy 13. [6][7][8][9] The mechanism of occurrence of monozygotic twins has been discussed by various authors, 4,10 but little is known about the mechanisms underlying heterokaryotypic twinning.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 There are only four reports of monochorionic twins discordant for trisomy 13. [6][7][8][9] The mechanism of occurrence of monozygotic twins has been discussed by various authors, 4,10 but little is known about the mechanisms underlying heterokaryotypic twinning. Parent of origin studies in our case indicated maternal origin of the trisomic chromosome.…”

Section: Discussionmentioning

confidence: 99%

“…This option has been advocated by other authors as well. 6 A chorionic villus sample in this situation may provide a false negative (normal karyotype) result in an aneuploid fetus, 6,11 and sampling a single amniotic sac will not exclude the possibility of aneuploidy in the second fetus. Early decision to perform amniocentesis in both the fetuses in our case resulted in timely diagnosis and allowed for thorough counselling before referral for selective fetal termination.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, good results after selective fetal termination using bipolar or laser cord coagulation have been described. 6 The risk of co-twin death/pregnancy loss and brain injury after single intrauterine death in monochorionic pregnancies has been estimated by O'Donoghue et al 14 Pregnancies in which single intrauterine death was spontaneous, occurred after fetoscopic placental laser, or resulted from selective termination by bipolar diathermy cord occlusion or interstitial laser were included in the study. The overall risks for co-twin loss and antenatal brain injury were estimated as 22.9% and 7.7%, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Monozygotic twins discordant for trisomy 13: counselling and management issues

et al. 2012

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The diagnosis and management of a heterokaryotypic monochorionic pregnancy, in which one of twins had trisomy 13, is presented. Monozygosity and discordant karyotypes were confirmed by amniocentesis of both the sacs. Radiofrequency ablation of the trisomic twin was successfully performed at 18-weeks gestation and the pregnancy ended at term with the birth of a healthy girl who remains well on follow-up at 12 months of age. We reiterate the importance of early amniocentesis of both the sacs in the presence of discordant fetal abnormalities and consideration of selective fetal termination to optimise the outcome of heterokaryotypic monochorionic twin pregnancies.

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Molecular Genetic Causes of Discordance in Monozygotic Twins

Czyz

Ramagopalan

2013

Encyclopedia of Life Sciences

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Although monozygotic (MZ) twins arise from the same gametes and a single zygote, they can at times reveal molecular genetic discordance. Differences in ploidy, chromosomal rearrangements and structural anomalies as well as different copy number variations (CNVs), point mutation discordance and genetic mosaicism have all been documented in MZ siblings. Depending on the type and magnitude, genetic discordance may lead to markedly different phenotypes. Traditionally, the best‐evidenced type of discordance encompasses a range of chromosomal abnormalities, partly due to their significant multiple effects on a phenotype. In contrast, surveying for single nucleotide polymorphism and CNV discordance globally poses more challenges. In the recent decades, growing evidence for low‐level CNV and point mutation discordance as well as mosaicism has amassed, although their frequency and phenotypic significance are yet to be established. High‐throughput sequencing strategies are likely to provide answers. Key Concepts: Despite stemming from the same zygote, monozygotic twins may develop genetic discordance. Postzygotic genetic alterations often result in genetic mosaicism in one or both of the twins. Confirmed genetic discordance in MZ twins encompasses mainly known disorders with clear or multiple/global effects, including five extremely rare cases of point mutations responsible for monogenic disorders and a range of chromosomal abnormalities as well as a few cases of trinucleotide repeat disorder discordance. The most common type of genetic discordance in MZ twins are aneuploidies, particularly 45,X0 monosomy and, to a lesser degree, trisomies 21, 15 and 13, whereas discordance for structural rearrangements is even less frequent. In MZ twins affected by aneuploidies, somatic mosaicism often plays a critical role in phenotypic discordance. Genome‐wide studies of SNP and CNV discordance in twins face technical difficulties and have not yet brought a definite answer, although there is limited evidence for very low‐level discordance. It will be challenging to fully ascertain the magnitude of genetic discordance in twins due to possible small‐scale SNP and CNV mosaicism across different tissues.

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Diagnosis and management of heterokaryotypic monochorionic twins

Cited by 60 publications

References 18 publications

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Non‐identical monozygotic twins, intermediate twin types, zygosity testing, and the non‐random nature of monozygotic twinning: A review

Monozygotic twins discordant for trisomy 13: counselling and management issues

Molecular Genetic Causes of Discordance in Monozygotic Twins

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