Perinatal/Neonatal Case Presentation

Monozygotic twins discordant for trisomy 13

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Monozygotic twins with discordant karyotypes are rare. We report a case of monozygotic twins discordant for trisomy 13 by amniocyte karyotypes. Ultrasound revealed multiple congenital anomalies in Twin A (47,XY,+13), none in Twin B (46,XY), and monochorionic-diamniotic placentation. Zygosity testing performed both prenatally and after birth supported monozygosity. Twin A died in the neontal period. Twin B survived and had normal physical examination, but peripheral blood karyotype revealed 20% mosaicism for trisomy 13. Monochorionic-diamniontic placentation with vascular anastomoses was confirmed by pathological examination. In this paper, we discuss the various mechanisms by which monozygotic twins may have discordant karyotypes. The surviving twin, structurally and developmentally normal at 6 months of age, will be monitored for potential complications of uniparental disomy of chromosome 13 and trisomy 13 mosaicism.


Monozygotic twins with discordant karyotypes are extremely rare and usually involve the sex chromosomes. Discordance for autosomal aneuploidy has been reported for chromosomes 13 and 21. Few reports have commented on the long-term outcome of the surviving apparently normal co-twin. We report a case of spontaneously conceived monozygotic male twins with discordant karyotypes—46,XY and 47,XY,+13—discuss the potential mechanisms of aneuploidy and present follow-up data about the surviving twin.


Ultrasonography of a 23-year-old G3P1011 woman at 13 weeks’ gestation revealed spontaneous monochorionic-diamniotic twins, with a cystic hygroma and complex cardiac lesion in Twin A, and an apparently normal Twin B. Karyotype by amniocentesis of Twin A revealed 47,XY,+13 in 15/15 cells, whereas Twin B had a normal 46,XY karyotype in 15/15 cells. Molecular testing at 12 different markers was consistent with monozygosity. The patient was offered selective termination of the trisomic Twin A by cord ligation, however, she declined. Fetal echocardiogram revealed a membranous ventricular septal defect, overriding aorta and pulmonary atresia in the trisomic Twin A. At 31 weeks’ gestation, the normal Twin B was diagnosed with intrauterine growth restriction based on an abdominal circumference in the third percentile. Because of spontaneous decelerations during antenatal testing, the patient was admitted for continuous fetal heart rate (FHR) monitoring and a course of steroids for fetal benefits. At 32 weeks’ gestation, a repeat cesarean was performed for non-reassuring FHR in the normal twin B. Placental pathology confirmed monochorionic-diamniotic placentation with vascular anastomoses.

Twin A had APGAR scores of 7 and 8 at 1 and 5 min, respectively, but was subsequently placed on mechanical ventilation because of worsening respiratory distress. Physical examination revealed multiple congenital abnormalities consistent with trisomy 13 (Figures 1, 2 and 3). Postnatal echocardiogram revealed double outlet right ventricle, pulmonary atresia, patent ductus arteriosus, atrial and ventricular septal defects with left-to-right shunt. Ultrasound examination showed possible intracranial hemorrhage, decreased sulcation pattern of the brain and mild bilateral hydronephrosis. Given the infant's poor prognosis, he was not a candidate for surgical cardiac repair. At the mother's request, all supportive measures were provided including mechanical ventilation, prostaglandin therapy and hyperalimentation until day of life 6, and the infant died shortly thereafter. No antemortem or postmortem genetic studies were performed except for repeat zygosity testing of peripheral blood showing that the twins were identical at 15 autosomal short-tandem repeats and one gender marker, indicating >99% probability of monozygosity.

Figure 1

Twin A with trisomy 13: physical examination is notable for micropthalmia, cleft palate, broad nasal bridge, long eye lashes and prominent fleshy glabella.

Figure 2

Twin A with trisomy 13: note low set ears, posteriorly rotated ears with helix fused to head.

Figure 3

Twin A with trisomy 13: note postaxial polydactyly of left hand.

Twin B had APGAR scores of 8 and 9 at 1 and 5 min, respectively. Physical examination was unremarkable. Peripheral blood karyotype revealed trisomy 13 in 5 out of 50 cells examined. This infant's hospital course was unremarkable, and he was discharged home on day 22 of life. Follow-up genetic evaluation at 6 months of life showed normal developmental progress and physical examination.


Monochorionic-diamniotic twins have traditionally been assumed to be monozygotic. However, there have been 13 cases of monochorionic twins conceived by in-vitro fertilization with discordant sex karyotypes that were confirmed to be dizygotic by molecular testing.1 This possibility was initially considered for our case, but zygosity testing was consistent with monozygosity using both amniocyte and peripheral blood samples.

Monozygotic twins discordant for autosomal aneuploidy are reported less frequently than those discordant for sex chromosomes, likely because of reduced fetal viability of the former, and the recognition of gender difference in the latter. Previous literature reports include monozygous twins discordant for monosomy 212 in one case, trisomy 213, 4, 5, 6 in four cases and trisomy 137, 8 in two cases.

There are several potential mechanisms that may give rise to discordant karyotypes in monozygous twins. Cleavage between 4 and 8 days post conception, after the establishment of the inner cell mass, leads to the most common type of monochorionic-diamniotic twins. Mitotic error may occur in an early cell division of a normal zygote around the time of cleavage and lead to an extra chromosome in that cell lineage. Alternatively, an initially trisomic zygote may experience spontaneous chromosome loss or ‘rescue’ in an early division.9 Both of these mechanisms have the potential for chromosomal mosaicism and also for uniparental disomy (UPD), where the two remaining chromosomes are derived from a single parent. UPD of chromosomes containing a large proportion of imprinted genes has been associated with phenotypic abnormalities, such as maternal UPD of chromosome 15 and Prader–Willi syndrome, and can also unmask autosomal recessive conditions. In contrast, chromosome 13 may contain few imprinted genes, as a review of the literature revealed four cases of paternal UPD 1310, 11, 12 and one case report of maternal UPD 1313 with normal phenotypes.

In cases of monochorionic twins with discordant karyotypes, one or both twins may exhibit mosaicism, possessing cells of diverse genetic consitution but derived from a single zygote, as seen in Twin B. Chimerism, defined as an organism made up of cells derived from more than one zygote, has been documented in rare cases of dizygous monochorionic twin gestation14. Monochorionic placentation is typically associated with shared circulation between twins. As such, amniocytes would be a more reliable source for detecting true mosaicism in monozygous twins compared with peripheral blood. In Twin B, although no trisomic cells were noted by amniocentesis, 20% mosaicism for trisomy 13 was detected in postnatal peripheral blood. Therefore, it is not clear whether Twin B has low level mosaicism undetected by amniocentesis, yet appears phenotypically normal, or that the trisomy 13 cell line in peripheral blood is the result of transfer through vascular anastomoses from the trisomic co-twin. Individuals with mosaicism for trisomy 13 can have a variable phenotype ranging from typical trisomy 13 syndrome to apparently normal phenotypes independent of the degree of mosaicism in peripheral blood or tissue.15 The possibility for mosaicism will always exist for Twin B, regardless of the results of repeated genetic testing. Therefore, his growth and development will need to be monitored closely.

In summary, we present a rare case of monozygotic twins with discordant karyotypes for trisomy 13. We conclude that in monochorionic twin pregnancies with fetal abnormalities identified in one twin, genetic testing should be considered for both twins. Further, if discordant karyotypes are detected, even the phenotypically and/or chromosomally normal twin will need to be followed and monitored carefully for the development of abnormalities due to the potential for UPD and mosaicism.


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Correspondence to K Wong Ramsey.

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Ramsey, K., Slavin, T., Graham, G. et al. Monozygotic twins discordant for trisomy 13. J Perinatol 32, 306–308 (2012) doi:10.1038/jp.2011.123

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  • trisomy 13
  • heterokaryotypic pregnancy
  • discordant twins
  • chromosomal mosaicism
  • chimerism
  • trisomy rescue

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