Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of autosomal trisomies

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0·72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0·8 MoM and 20 per cent were over 1·0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0·70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.     

Normal development in two six-year-old boys born after prenatal diagnosis of trisomy 20 mosaicism

Prenatal diagnosis of trisomy 20 mosaicism was made in two pregnancies by chromosome analysis of cultured amniotic fluid cells. In both cases, the pregnancy continued to term and a healthy male infant was delivered. Regular assessments up to the age of 6-5 years revealed normal physical and intellectual development in both children.     

A revisit of trisomy 20 mosaicism in prenatal diagnosis—an overview of 103 cases

One hundred and three cases with prenatal diagnosis of trisomy 20 mosaicism through amniocentesis were reviewed. Approximately 90 per cent (90/101) of the cases were associated with grossly normal phenotype. It is likely that, in the majority of cases, cells with trisomy 20 were extraembryonic in origin or largely confined to the placenta. However, in some cases, the cells with trisomy 20 were confined to certain specific fetal organs or tissues such as kidney, skin, etc. Cytogenetic follow-up studies in liveborns should include a culture from urine sediment.     

Vaginal bleeding in pregnancies associated with fetal Down syndrome

It has been suggested that vaginal bleeding in pregnancy is associated with an increased risk of fetal Down syndrome. To investigate this, information on vaginal bleeding, collected at the first antenatal visit, was abstracted from the medical notes of 70 pregnancies associated with Down syndrome and 140 unaffected controls matched for maternal age. Fourteen cases (20 per cent) and 23 controls (16 per cent) had some evidence of bleeding (relative risk estimated as the odds ratio= 1.3; P=0.26, one-sided; 95 per cent confidence interval 0.6–2.8). When these results were pooled with those from the two other controlled studies already published the combined relative risk estimate was 1.8 (P=0.02, two-sided; 95 per cent confidence interval 1.1–3.0). On the basis of present evidence, there is some reason to regard vaginal bleeding prior to the first antenatal visit as a risk factor for Down syndrome but the association and its biological significance remains uncertain.     

Prenatal diagnosis of mosaic trisomy 9

Mosaic trisomy 9 was detected in an amniotic fluid cell culture from a 40-year-old woman evaluated because of advanced maternal age. After counselling, parents elected to terminate the pregnancy. On autopsy the fetus was found to have hydrocephalus and a single kidney. The diagnosis of trisomy 9 mosaicism was confirmed in cultured skin fibroblasts. This is the third reported case of trisomy 9 mosaicism diagnosed prenatally.     

Prenatal diagnosis of trisomy 21 and X/XX sex chromosome mosaicism

Double aneuploidy involving Down syndrome and Turner syndrome is a rare chromosomal abnormality presumed to occur with a frequency of about 1 in 2 million births. Twenty-one cases of this combined anomaly have been reported and two infants were born with this anomaly after a mistake in prenatal diagnosis. We report the first prenatal diagnosis of Down syndrome combined with Turner mosaicism and suggest that this polysyndrome may be more common than previously estimated. We, therefore, wish to alert cytogenetic laboratories performing prenatal diagnoses of the potential risks of misdiagnosis of this polysyndrome if banding is not performed and if a sufficient number of mitotic cells are not analysed.     

Prenatal diagnosis of trisomy 18 mosaicism

Trisorny 18 mosaicism was found in multiple primary cultures of amniotic fluid cells and subsequently confirmed by chromosome analysis of several tissues derived from the aborted fetus. The overall frequency of the minority cell line was 25 per cent in the amniotic fluid cultures and 28 per cent in the fetal tissues although much intertissue variations were noted.     

Rapid prenatal diagnosis of trisomy 18 and triploidy in interphase nuclei of uncultured amniocytes by non-radioactive in situ hybridization

Two biotinylated chromosome-specific DNA probes were used to quantify the number of chromosomes 18 and 1 in uncultured amniocytes. Thirty-three samples of uncultured amniocytes were hybridized with a chromosome 18-specific DNA probe. Uncultured cells from two of the 33 samples were also hybridized with a chromosome 1-specific probe. Thirty of the samples were disomic with respect to chromosome 18; two samples were trisomic with respect to chromosome 18, and one sample was trisomic with respect to chromosomes 1 and 18. The two cases of trisomy 18 and the single case of triploidy were identified on uncultured celis within 48-72 h after amniocentesis. They were found among five samples from pregnant women who had amniocentesis because of an ultrasonographically identified fetal malformation. A trisomic karyotype could be diagnosed with certainty in uncultured amniocytes because the majority of the responding nuclei exhibited three hybridization signals. In normal cells, the majority of nuclei exhibited two signals. In no cases was there discordance between the genotype as predicted by in situ hybridization and that determined by cytogenetic analysis.     

Prenatal diagnosis of trisomy 9 mosaic presenting as a case of Dandy-Walker malformation

Trisomy 9 syndrome is a rare chromosomal anomaly associated with specific patterns of multisystem dysmorphism and occasional central nervous system (CNS) malformations, the most common being the Dandy-Walker malformation. Milder anomalies are usually seen with trisomy 9 mosaicism. We report what we believe to be the first case of a baby with an isolated Dandy-Walker malformation which was diagnosed prenatally and was subsequently found to have a trisomy 9 mosaic syndrome.     

The significance of prenatal diagnosis of choroid plexus cysts

A case is described of the prenatal diagnosis of choroid plexus cysts at 17 weeks' gestation which persisted beyond 36 weeks but could not be detected after delivery. At birth the child was found to have trisomy 18.     

Prenatal diagnosis of trisomy 9 mosaicism: Two new cases

We present two prenatal cases of trisomy 9 mosaicism, both of which presented intrauterine growth retardation (IUGR) and other abnormal ultrasound findings. In case A, mosaicism was found in amniotic fluid cell cultures, of which 65 per cent were trisomic cells, on average. In case B, trisomic cells were present in amniotic fluid cell cultures (12 per cent) but none were found in fetal cord blood. After autopsy, cytogenetic findings were confirmed in different tissue cultures. It is concluded that echographic indicators are a very useful tool for a correct prenatal diagnostic interpretation of trisomy 9. Suspected trisomy 9 mosaicism always requires further investigation and fetal cord blood cytogenetic analysis may not be considered as providing an accurate diagnosis of fetal trisomy 9.     

Postnatal placental confirmation of trisomy 2 and trisomy 16 detected at chorionic villus sampling: A possible association with intrauterine growth retardation and elevated maternal serum alpha-fetoprotein

Detection of trisomy 2 and trisomy 16 mosaicism through chorionic villus sampling (CVS) is not an infrequent finding. We describe here two cases, one of non-mosaic trisomy 2 and the other of high level mosaicism for trisorny 16. Amniocentesis in both cases demonstrated non-mosaic 46,XY karyotypes. Each pregnancy continued to delivery of liveborn, normal-appearing boys; both pregnancies were complicated by severe intrauterine growth retardation (IUGR). Postnatal studies of placental biopsies in both cases confirmed the original CVS findings, whereas cord blood karyotypes were normal in both boys. Both children have demonstrated adequate catch-up growth.     

Prenatal diagnosis of trisomy 12 mosaicism: Physical and developmental follow-up

Follow-up evaluations were performed on a child at the ages of 2 years 8 months and also at 5 years who had been found on prenatal amniocentesis to be mosaic for trisomy 12. Eight of 36 colonies (22 per cent) were trisomy 12 at amniocentesis, with the remaining colonies showing a normal female karyotype. Cord blood, amnion, chorion, placental, and skin fibroblast chromosome studies failed to show any further evidence of a trisomy 12 cell line. At her evaluations, the child had normal physical and neurological findings. Psychomotor development was appropriate for age on screening.