Confined placental mosaicism for trisomy 2 with intrauterine growth retardation and severe oligohydramnios in the absence of uniparental disomy in the fetus

We have recently seen a pregnancy in which ultrasound scanning of the fetus showed from as early as 12 weeks that the fetal growth was slower than usual with associated oligohydramnios. At 14 weeks of gestation when amniocentesis would normally be carried out, there was already marked oligohydramnios. The fetus was severely curled up, making fetal measurement difficult. Due to the reduced volume of liquor, transabdominal chorionic villus sampling (CVS) rather than amniocentesis was performed at 17 weeks. The CVS karyotype showed trisomy 2 in both direct preparation and culture (43 cells). No cells with a normal karyotype were seen, although they were presumed to be present in the fetus. The pregnancy was terminated at 19 weeks using prostaglandin pessaries and an evacuation of the uterus was then performed. The fetus showed head-sparing asymmetrical growth retardation with body measurements corresponding to 16 weeks’ gestation. Post-mortem examination showed a male fetus with no significant anatomical abnormality. Fetal muscle samples from the left calf, right thigh, and right shoulder were cultured and all revealed a 46,XY karyotype (60 cells). Trisomy 2 was not detected in the fetus. Culture of placental tissue was unsuccessful. As a trisomic conceptus may result in a fetus with uniparental disomy (UPD), DNA was prepared from peripheral blood samples from both parents and from the fetal muscle. PCR using SSR (simple sequence repeat polymorphisms) was used to determine the parent of origin of the two chromosomes 2 in the fetus and of the extra chromosome 2 in the placenta. Markers D2S144, D2S172, and GCG were fully informative and showed clearly that in the fetus, one allele was derived from each parent and that in the placenta, one allele was from the father and two were from the mother. This finding makes it clear that the fetus did not have UPD and that the error which gave rise to the trisomy was most likely a maternal meiosis 1 error with a subsequent correction in the fetal cell lineages. The methods used for the PCR analysis were standard ones. In brief, primers were kinased with 32P; PCR was performed for 29 cycles; and PCR products were analysed on denaturing 6 per cent polyacrylamide gels. DNA was prepared from parental peripheral blood, fetal muscle, and placenta by standard methods. Primers were obtained from Research Genetics in Birmingham, AL (U.S.A.). We feel that this case warrants a brief mention in the literature since it represents the only known case in which non-mosaic trisomy 2 was demonstrated in the placenta and UPD for chromosome 2 was ruled out as a cause of IUGR in the fetus. Kalousek (1994) reviewed reported cases of confined placental mosaicism (CPM) including 22 cases of CPM for trisomy 2 of which three cases had IUGR and two cases resulted in fetal death. Most cases appear to have had a normal outcome. Since that report, there have been three reports of maternal UPD 2 in babies. In our case (Harrison et al., 1995), the baby had growth failure and fetal distress with oligohydramnios but survived and is now alive, although growth remained below the tenth centile. In the case of Bernard et al. (1995), the baby suffered from IUGR and died soon after birth. In the case of Webb et al. (1996), severe IUGR was followed by livebirth and normal development at 6 months. In light of these three cases it might be tempting to consider that maternal UPD for chromosome 2 may have had a role in the poor outcome, not only in these three cases but also in the five cases summarized by Kalousek. Robinson et al. (1996) have, however, recently suggested that a meiotic origin of trisomy *Correspondence to: Barbara Gibbons, Cytogenetics Laboratory, Gleneagles Hospital Singapore, 6A Napier Rd, 3rd Level, Annexe Block, Singapore 258500.