Trisomy 16 confined to the placenta

Two cases with trisomy 16 confined to the placenta are presented. Prenatal diagnosis was indicated because of fetal growth retardation. In case 1, a phenotypically normal but small-for-date boy was born. In case 2, the fetus turned out to be triploid on cordocentesis. In both instances the trisomy 16 was recovered from the placenta. Recovery indicates that the abnormality was present in the placenta during the time of fetal growth retardation, which supports an aetiological relationship. Strict appliance of the current models cannot readily explain the observed discrepancies. In case 2, a chimeric placenta as a result of a vanishing twin is assumed. Cases of placental trisomy 16 published after 1988 are reviewed. It is concluded that confined placental trisomy 16 can cause intrauterine growth retardation if present in both the direct preparation and the villus culture. The chances of finding a chromosomally abnormal fetus (mosaic trisomy 16, triploidy) after diagnosis of trisomy 16 in chorionic villi are low but warrant further investigations.     

46,XX/46,XY chromosome complement in amniotic fluid cell culture followed by the birth of a normal female child

Experience indicates that the most likely explanation for a mixture of 46,XX/46,XY cells in an amniotic fluid sample is that of maternal cell contamination and that a normal male child is to be expected at birth. We report the birth of a normal female child following prenatal diagnosis of such a mixture. Extensive postnatal studies failed to reveal an XY cell line. The possible sources of the XY cell line are discussed, as are the various techniques that were applied in an effort to discover it's origin. Cross-contamination of samples could be ruled out and there was no evidence of an unsuspected twin pregnancy. It is clear from this case that not all 46,XX/46,XY results obtained in amniotic fluid can be assumed to represent maternal cell contamination and some effort should be made to eliminate other potential sources for such a mixture.     

Fetoscopy and fetal blood sampling in the management of a twin pregnancy with 45,X/46,XX amniotic fluid cell mosaicism and a suspected fluid sampling error

A 37 year-old woman with a twin pregnancy underwent amniocentesis to exclude fetal chromosome abnormality. The results indicated that both fetuses were mosaics, with 45,X and 46,XX, cell lines. Since it was suspected from the ultrasound scan that the twins were dizygotic, the result was questioned. Fetoscopy and fetal blood sampling were performed and karyotyping the fetal lymphocytes confirmed that one twin was indeed a mosaic, 45,X/ 46,XX, but the other had a normal male chromosome complement. The pregnancy resulted in the birth of a phenotypically normal girl, in whom the 45,X/46,XX mosaicism was confirmed, and a normal boy.     

Prenatal diagnosis,fetal pathology and cytogenetic analysis of A 46,XX/47,XX, + 15 mosaic

Mosaic trisomy 15 was prenatally diagnosed on amniotic fluid cells from two consecutive amniocenteses and was confirmed on cells from five different fetal tissues. The proportion of normal versus trisomic cells was consistently higher in the amniotic cell cultures and-with one exception-in the fetal tissues, while serial subcultures gave different results. The slightly atypical external features and internal malformations of the affected fetus as compared to the only clinical observation from the literature are not unusual enough to allow the delineation of a specific malformation pattern.     

Trisomic 22 placenta in a case of severe intrauterine growth retardation

We describe a case in which a trisomic 22 placenta could be the cause of severe growth retardation in a chromosomally normal female fetus. At amniocentesis a mosaic 46,XX/ 47,XX, +22 was observed in amniotic fluid specimens sampled on two different occasions, while fetal blood from a diagnostic cordocentesis revealed a normal chromosome constitution. Postnatal studies showed the consistent presence of trisomic 22 cells in the placenta, while only normal metaphases were found in amnion, blood, and fibroblast cultures.     

SPONTANEOUS RESOLUTION OF CYSTIC HYGROMA IN A 46,XX NORMAL FEMALE

We report a case of nuchal cystic hygroma with spontaneous resolution detected by ultrasound examination at 13 weeks' gestation. Fetal karyotype and amniotic fluid alphafetoprotein levels were normal. Extreme caution in evaluating this situation is stressed.     

Fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X)

Fetal blood sampling has been used in the genetic work-up of twin gestations for rapid karotyping. We present a case of twins which on ultrasound evaluation revealed hydrops fetalis in one twin and a normal second twin. Fetal blood sampling revealed the presence of mosaicism for 46,XY/45,X in both twins. HLA antigen testing showed the twins to be identical. The patient elected pregnancy termination. Blood chromosomal analysis after delivery revealed both twins to have 46,XY/45,X mosaicism, but the twin with signs of hydrops fetalis had tissue chromosomes of 45,X and the normal twin had tissue chromosomes of 46,XY. Amniotic fluid chromosomal analysis revealed 46,XY in twin A and 45,X in twin B. This represents a case of identical (monozygotic) twins with sex discordance. In this case, there was the probable occurrence of post-zygotic chromosomal non-disjunction leading to the discordancy of the sex in this set of twins. With the presence of vascular communication in monozygotic twins, there is the possibility of exchange of blood in monozygotic twins and the result of blood chimerism in twins.     

Prenatal diagnosis of a 46,XX/47,XX, +12 mosaic

A case of true mosaicism 46,XX/47,XX,+ 12 was diagnosed prenatally. The pregnancy was terminated in the 21st week of gestation and the aberrant cell line was rediscovered in cultured fetal tissue. However, a detailed examination of the fetus did not disclose any significant physical malformation.     

Prenatal diagnosis of mosaicism 46, XX/46, XX, −21, +t(21q21q)

Mosaicism for a structural chromosome abnormality in amniotic cell cultures indicative of true fetal mosaicism is a rare event. In addition to the laboratory findings the clinical interpretation for counselling in such cases is based on observation of the same abnormality in liveborns as well as previous experience with prenatal diagnosis of the same or similar abnormalities. We report here the prenatal diagnos is of 46,XX/46,XX,−21,+t(21q21q) which was confirmed in fetal skin cell and amnion cell cultures.     

Prenatal diagnosis of 45,X/46,XY mosaicism—A review and update

A total of 54 cases with prenatal diagnosis of 45,X/46,XY mosaicism was reviewed. Of 47 cases with information on phenotypic outcome, 42 cases (89·4 percent) were reported to be associated with a grossly normal male phenotype. Three cases (6·4 percent) were diagnosed as having mixed gonadal dysgenesis with internal asymmetrical gonads. Two other cases were questionably abnormal. In 40 cases with successful cytogenetic confirmatory studies, the overall rate of cytogenetic confirmation of 45,X/46,XY from tissues derived from fetus/liveborn/placenta was 70·O per cent. This review shows a major difference in the phenotypic outcome between postnatal diagnosis and prenatal diagnosis. Due to the ascertainment bias, almost all known patients with postnatal diagnosis of 45,X/46,XY mosaicism are phenotypically abnormal. Therefore, caution must be used in translating information derived from postnatal diagnosis to prenatal diagnosis. This review calls for collection of more data on 45,X/46,XY mosaicism diagnosed prenatally, more long-term follow-up of liveborn infants, and pathological studies of all abortuses. Emphasis is placed also on the importance of genetic counselling, ultrasound examination, and cytogenetic confirmation.     

Resorbed co-twin as an explanation for discrepant chorionic villus results: Non-mosaic 47,XX, +16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal blood

Non-mosaic trisomy 16 was observed in chorionic villus cytotrophoblasts (direct) as well as cultured mesenchymal core cells derived from the pregnancy of a 38-year-old woman. Chromosome preparations from amniotic fluid and neonatal cultures (cord blood) were 46,XX. Normal fetal growth as determined by serial ultrasound examinations occurred throughout the pregnancy, which resulted in a healthy 2724 g female. Multiple biopsies taken from the umbilical cord, placental cotyledons, and fetal membranes were 46,XX. However, a placental nodule and three of six cultures initiated from membranes (amnion and chorion) showed 46,XX/47,XX, + 16 mosaicism. We propose that the trisomy 16 cells arose from residual villi derived from a trisomic cotwin that never developed. This case further demonstrates that normal fetal growth may presage normal outcome irrespective of cytogenetic findings in cytotrophoblasts (direct) and cultured mesenchymal core cells.     

Placental mosaicism in a case of 46,XY, −22, +t(22;22)(p11;q11) or i(22q) diagnosed at amniocentesis

46,XY, −22,+t(22;22)(p11;q11) or i(22q) was diagnosed in 15/15 cells from two cultures from the amniotic fluid culture of a 31-year-old patient whose fetus demonstrated cystic hygroma on ultrasound. Cytogenetic studies performed on fetal skin from the abortus revealed the same karyotype as that seen on amniocentesis, but the placenta demonstrated a 46,XY,46,XY, −22,+t(22;22) or i(22q) mosaicism, with 65 per cent of the cells being 46,XY. This case provides an example of placental mosaicism for a normal male karyotype, while the fetus demonstrated non-mosaic trisomy 22.     

Chromosome mosaicism of the placenta—a cause of developmental failure of the fetus?

Fourteen (2.5 per cent) of 568 chromosome preparations after CVS showed discrepancies between the placental and fetal karyotype, mainly due to placental mosaicism. The presence of a second cell line within the placenta was confirmed in all but one case, in which cytogenetic reinvestigations were carried out. Our clinical data indicate that severe developmental retardation in the newborn is not to be expected if only the placenta carries the chromosomally abnormal cell line.     

Mosaicism of 46,XX/47,XX,+9/47,XX,+?mar in the same amniotic fluid with apparent loss of one cell line after delivery

A 46,XX; 47,XX,+9; 47,XX, + ?mar karyotype was detected in an amniotic fluid cell culture and confirmed in a subsequent fetal blood sample from a 40-year-old woman. After termination of the pregnancy, none of the 186 mitoses obtained from a second blood sample was trisomic for chromosome 9 (p<0.001). Selection against cells containing trisomy 9 is postulated to explain the disappearance of the lymphocyte clone.     

Prenatal diagnosis of 46, XX/47, XXY mosaicism: A case report

A case of 46,XX/47,XXY mosaicism was diagnosed at 22 gestational weeks by amniocentesis and fetal blood sampling. After genetic counselling, the couple elected to have the pregnancy terminated. Culture of the fetal skin and both gonads confirmed the prenatal diagnosis. In external appearance, the abortus had no remarkable findings except hypospadia. Histology of both gonads showed testicular tissue without evidence of ovarian components.     

A second case of intrauterine growth retardation and primary hypospadias associated with a trisomy 22 placenta but with biparental inheritance of chromosome 22 in the fetus

We report a case of severe intrauterine growth retardation (IUGR) and hypospadias in association with trisomy 22 diagnosed following chorionic villus sampling (CVS). Subsequent analysis of amniotic fluid cultures showed a normal male karyotype, 46,XY. As a previous case had been reported with similar abnormalities, in association with maternal uniparental disomy (UPD) 22, molecular studies were also performed. Microsatellite marker studies showed biparental inheritance. Follow-up studies after delivery showed a normal cell line in lymphocytes with the trisomy appearing to be confined to the placenta. The present case concurs with other earlier reports that maternal UPD for chromosome 22 has no impact on the phenotype. The features seen in the fetus are most likely the result of placental dysfunction due to trisomy, tissue-specific mosaicism and/or the effects of local growth restriction. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of 45,X/46,XX mosaicism in the fetus. Should the pregnancy be terminated?

45,X/46,XX True mosaicism was found in the amniotic fluid cell culture study in our patient and was confirmed by rapid fetal blood karyotyping. Elective termination of the pregnancy revealed a morphologically normal female fetus with true mosaicism but no features of Turner's syndrome.     

Biamnial elevated alpha-fetoprotein and positive acetylcholinesterase in twins,one with anencephaly

Anencephaly in twin B was accompanied by elevated amniotic fluid alpha-fetoprotein (AFP) and a positive acetylcholinesterase (AChE) band on gel electrophoresis in both twin sacs, although twin A was normal. AChE results did not help distinguish the false positive AFP in this set of twins, implying that AChE may diffuse transamniotically as has been previously postulated for AFP. In light of the low concordance rate for neural tube defects in twins, patient counselling in this situation must include the information that AFP and AChE may be falsely elevated in normal twin when the other twin has a neural tube defect.