R. Chaki

DOWN'S SYNDROME SCREENING MARKER LEVELS FOLLOWING ASSISTED REPRODUCTION

Maternal serum α‐fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1·09 and 0·92 multiples of the normal gestation‐specific median (MOM) based on a total of 34 582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1·05 MOM) and a significant decrease when Pergonal was used (0·93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0·92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Downs syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Molecular cytogenetic studies in three patients with partial trisomy 2p, including CGH from paraffin-embedded tissue.

We report on three cases of partial trisomy 2p in which the identification and exact localization of the duplicated chromosome segment was possible only by application of molecular cytogenetic techniques. These included fluorescence in situ hybridization by use of wcp2, N-myc, and subtelomeric 2p probes and comparative genomic hybridization with DNA isolated from blood samples, frozen fetal tendon, and formalin fixed, paraffin-embedded fetal lung tissue. Two of the cases concerned fetuses of gestational week 20 and 24 with duplication of nonoverlapping terminal (2pter-->p24) and more proximal (2p25-->p23) segments and with distinctly different phenotypes. The third case was due to a de novo inverted duplication of 2p25-->p23, with loss of the subtelomeric region of 2p. This 53-month-old girl was a Bloom syndrome carrier. The patient had prenatal growth failure, borderline microcephaly, dilated lateral horns of the cerebral ventricles, transient cortical blindness, myopia, muscle hypotonia, and dilatation of the left renal collecting system. Dermal cysts were found on the glabella, the soles of both feet, and the vocal cord, causing respiratory embarrassment. Previously reported cases of pure trisomy 2p are reviewed, in an attempt to correlate clinical findings to overlapping regions in 2p. These cases illustrate the effectiveness of molecular cytogenetic methods in resolving subtle chromosomal aberrations in order to coordinate more accurately a chromosome regionspecific phenotype.

Use of interphase fluorescence in situ hybridization in third trimester fetuses with anomalies and growth retardation

In the last few years, attention has been focused on the use of interphase fluorescence in situ hybridization (FISH) for prenatal diagnosis with chromosome-specific DNA probes in the second trimester. This technique is accurate, rapid, and detects the most common aneuploidies. We present a preliminary study using FISH technique on uncultured amniotic cells derived from 30 fetuses with ultrasonographic evidence of intrauterine growth retardation (IUGR) in the third trimester. Fifteen fetuses were males and 15 were females. Seven fetuses (23.3%) had abnormal chromosomal constitution: five (18.6%) had trisomy 21, one (2.35%) had trisomy 18, and one (2.35%) showed a mosaic trisomy 18. No abnormalities were detected in the other 23 fetuses. Amniocentesis combined with FISH appears to be a safe, rapid, and accurate alternative to blood sampling in the third trimester, reducing the clinical and emotional stress of the time required to complete chromosome analysis by routine cytogenetics.

EFFECT OF GRAVIDITY ON MATERNAL SERUM MARKERS FOR DOWN'S SYNDROME

The effect of gravidity on maternal serum α‐fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27 592 women being screened for Downs syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5·9 per cent lower than in those tested in their first pregnancy (P<0·0001) and the median uE3 level was 3·9 per cent lower (P<0·0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Downs syndrome screening detection and false‐positive rates.

Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis

We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

Two de-novo balanced autosomal translocations after intracytoplasmic sperm injection.

incipient intrauterine growth retardation, our patient chose to have her pregnancy terminated. Labour was induced at 26 weeks by extra-amniotic administration of prostaglandin F2 after intracardiac potassium chloride injection. A macerated 740 g (25th percentile) fetus was delivered. Macroscopic pathological assessment of the organs, excluding the brain, showed no malformation. The karotype was confirmed by peripheral blood analysis. Although we cannot find a causal relation between ICSI and this rare chromosomal abnormality, and until more data on these pregnancies are obtained, we recommend amniocentesis to patients after ICSI.

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso‐enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso‐enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses. Copyright

The trisomy 4p syndrome: A case report

Partial trisomy of the short arm of chromosome 4 is considered to be a rare chromosomal disorder. Its clinical and dermatoglyphic features tend to make it a clinically recognizable syndrome. This paper describes a 2 year-old female child with the characteristic findings of frontal bossing, deep-set eyes, broad nasal bridge giving the appearance of hypertelorism, wide nares, midfacial hypoplasia, large dysplastic ears, prognathism and various hand and foot malformations.Chromosomal studies showed her to be trisomic for the distal two-thirds of the short arm of number 4. The etiology of this chromosomal aberration in most instances is unknown, but may occur as a result af an unbalanced translocation in one of the parents as in the case reported here.

Amniotic Fluid α-Fetoprotein Levels and Fetal Chromosomal Abnormalities

406 midtrimester amniotic fluid samples were examined for Α-fetoprotein (AFP) levels and fetal karyotyping. 44 cases with Down syndrome, 12 with Klinefelter syndrome and 14 with other chromosomal