Uncommon chromosomal mosaicism in chorionic villi

Three cases of unusual chromosomal mosaicism are reported for which the cytogenetic data show inconsistent findings between CVS and AC or fetal tissue, and which cannot be explained simply by non-disjunction. For case 1, in CVS the karyotype was 46,XY, whereas lymphocytes and fibroblasts revealed 69,XXY. DNA fingerprinting indicated one paternal and two maternal chromosome sets, the latter most probably due to omission of maternal meiosis II. For case 2, in CVS mos 46,XX/47,XX,+mar de novo was observed. Amniotic fluid cells had the karyotype 46,XX. The origin of the marker chromosome might be explained by at least two events of unknown order (a somatic chromosome/chromatid deletion and non-disjunction of the homologous chromosome). In case 3 (CVS: mos 46,XY/46,XY,19q+ de novo; amniotic fluid cells, lymphocytes, and fibroblasts: 46,XY), the surplus of chromosome material in 19q+ might be explained on the basis of a somatic translocation. The idea of a chimera is less convincing, as the mosaic finding is restricted to one tissue. Furthermore, there was no hint of a vanishing twin. Hitherto, no case of structural chromosome mosaicism in CVS has been reconfirmed in fetal tissues.     

Vitamins,folic acid and neural tube defects: Comments on investigations in the United States

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.     

Clinical and pathological factors in spontaneous abortion following chorionic villus sampling

Twenty-nine cases of spontaneous abortion following first-trimester chorionic villus sampling (CVS) were reviewed out of a series of 722 patients. Of the 29 cases, there were only four abnormal CVS results. Pathological examination was performed in 79 per cent of cases, and this did not identify any characteristic pathological feature associated with spontaneous abortion after CVS. There was no obvious difference in the pathological features following the transabdominal (TA) or the transcervical (TC) methods. The majority of miscarriages occurred within 4 weeks of the procedure, but 38 per cent of cases aborted between 7 and 14 weeks after CVS. The TC method was used in 22 patients; the TA in 6; and both methods in 1 patient. The TA method was associated with a significantly lower fetal loss rate than the TC method (TA 2 per cent, TC 9 per cent, p < 0.001).     

Estimating the risk of a fetal autosomal trisomy at mid-trimester using maternal serum alpha fetoprotein and age: A retrospective study of 142 pregnancies

Risks appropriate for mid-trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha-fetoprotein (AFP) levels at 16–20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age-related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at midtrimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13)and 113 000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy. A mid-trimester cut-off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow-up (false-positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false-positive rate if age 35 years and over is used as the sole criterion for selection of at-risk pregnancies.     

Evidence of a second gamete fusion after the first cleavage of the zygote in a 47,XX, + 18/70,XXX, + 18 mosaic. A remarkable diploid-triploid discrepancy after CVS

A 70,XXX, +18 karyotype was found by chorionic villus sampling, while the fetal fibroblast culture of the affected fetus revealed a 47,XX,+ 18 karyotype. From several possible mechanisms, we assume that a second gamete fusion occurred after the first cell division of the zygote. According to this interpretation, the mosaicism arose in very early pregnancy (at the two-cell stage). This discrepancy can therefore be explained by selection pressure, due to the differentiation processes in the embryonic tissues.     

Molecular cytogenetic characterization of marker chromosomes found at prenatal diagnosis

The nature and origin of two de novo small marker chromosomes found at prenatal diagnosis were determined by fluorescence in situ hybridization using chromosome centromere-specific probes and chromosome-specific plasmid libraries. One marker was found in a mosaic state and was shown to be an i(18p). The second marker was characterized as an inv dup(22). We conclude that molecular cytogenetic analysis contributes to the identification of marker chromosomes and therefore facilitates genetic counselling and decision-making for the parents.