Prenatal diagnosis of mosaic 4p – in a fetus with trisomy 21

Mosaicism for the Wolf-Hirschhorn syndrome, del(4)(p16), is extremely rare and has not been reported in association with a numerical chromosome abnormality. We report the prenatal diagnosis of mosaic del(4)(p16) and non-mosaic trisomy 21 in a 16-week female fetus. The pregnancy ended in spontaneous abortion at 34 weeks secondary to fetal demise. The fetus had features of both 4p – and trisomy 21.     

Prenatal exclusion of stickler syndrome

Stickler syndrome is an autosomal dominant disorder of the connective tissue which includes ocular and systemic manifestations. We report on a large kindred in which we were able to demonstrate very tight linkage between the disease and the type II collagen gene (COL2A1) (LOD score 3·91 at θ=0). In a family in which the father and one of his daughters were severely affected, DNA analysis from a chorionic villus sample demonstrated that the fetus possessed the normal allele of COL2A1. Thereafter a normal child was born.     

Incremental cost-effectiveness of incorporating oestriol evaluation in down syndrome screening programmes

As screening for Down syndrome becomes increasingly sophisticated, it is important to evaluate the newer technologies in terms of their cost-effectiveness. One recent addition to Down syndrome screening programmes is maternal serum unconjugated oestriol (uE₃), especially when used in conjunction with maternal serum α-fetoprotein and human chorionic gonadotropin. Using assumptions used in a California proposal to justify an expanded screening programme for Down syndrome, we calculated both the average and the incremental cost-effectiveness of adding uE₃. Using the base case assumptions, including an $8 fee for the uE₃, the incremental cost-effectiveness of adding uE₃ to the proposed California programme is $119 100 per case detected, a value that compares favourably with other Down syndrome screening programmes. The sensitivity analysis supports this conclusion over a wide range of assumptions. However, because of the uncertainty with some key data, it is still too early to fully support the inclusion of uE₃ in Down syndrome screening programmes.     

Patients' attitudes following chorionic villus sampling

The attitudes of 190 patients who had undergone chorionic villus sampling (CVS) were assessed by means of a questionnaire. One hundred and fifty-two patients replied of whom 68 (45 per cent) were referred because of increased maternal age and in the other 84 cases the indications included previous chromosomal abnormalities, fetal sexing, DNA analysis, and biochemical analysis. One hundred and twenty-two patients had a transcervical procedure, 24 had a transabdominal, and six patients required both procedures. One hundred and forty-one patients (93 per cent) reported CVS to be a satisfactory procedure, and the same percentage thought earlier diagnosis was beneficial. Thirty-nine patients (81 per cent) reported a better experience with CVS than with a previous amniocentesis. A majority of patients (93 per cent) wished a CVS in a future pregnancy and 137 patients (97 per cent) would accept a risk of miscarriage from the procedure of twice that quoted for amniocentesis (1 per cent).     

Prenatal diagnosis of cystinosis utilizing chorionic villus sampling

The prenatal diagnosis of cystinosis is currently based on the increased amount of free-cystine present in amniotic fluid cells. Amniocyte cultures must be grown for at least 2 weeks to obtain sufficient cells for such measurements. Thus, the diagnosis cannot be made until close to 20 weeks gestational age by this method. We report a case in which chorionic villi were used for direct cystine measurement resulting in the in utero diagnosis of cystinosis at 9 weeks gestational age. The diagnosis was confirmed by the study of cultured chorionic villus cells, and of the 10-week abortus.     

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.     

Rapid prenatal diagnosis of Patau's syndrome in a fetus with an abdominal wall defect by 72 hour culture of cells from amniotic fluid

A woman in the 32nd week of pregnancy was referred for investigation because of fetal abnormalities, including an abdominal wall defect, detected by ultrasonography. In view of the increased risk of chromosome abnormality, amniocentesis was performed to enable informed decisions about the management of the pregnancy and delivery to be taken. Cells from the liquor were inoculated into standard lymphocyte culture medium and incubated for 72 h. Slides with a high mitotic index and good quality metaphases, comparable to those from a blood culture, were obtained after harvesting. Cytogenetic analysis showed the karyotype to be 46,XY,—14,+t(13ql4q), which is consistent with Patau's syndrome. This technique appears to be an option for rapid karyotyping in cases of abdominal wall defect, where a chromosomal abnormality is suspected.     

Introduction of early amniocentesis to routine prenatal diagnosis

With growing awareness of the problems associated with prenatal cytogenetic diagnoses after CVS, attempts have been made to provide early amniocentesis as an alternative to CVS. Since 1990, at our clinic the gestational age limit for routine diagnostic amniocentesis has been successively lowered, first to 14 and then to 13 weeks of gestation. Thus, 811 prenatal diagnoses were performed after early amniocentesis at 13 weeks (n = 217) and at 14 weeks of gestation (n = 594). No problems were encountered. Culture failure was never observed in the early samples. Using the criteria ‘number of colonies’ and ‘culture duration until harvest’, early samples taken at 14 weeks did not differ significantly from the controls after standard amniocentesis performed at 15 and 16 weeks, respectively, whereas a minority of samples taken at 13 weeks experienced some delay in culturing. However, in each group at least 85 per cent of samples led to a diagnosis fulfilling our standard criteria of a safe diagnosis (at least 20 metaphases of at least five colonies from at least one primary culture after trypsinization) within 15 days. Some differences between the different groups can be recognized: culture duration of less than 11 days tends to be increasing after standard amniocentesis, whereas long culture duration (more than 20 days) is more often associated with early amniocentesis. However, this trend is only minimal and did not result in an increased risk of missing a diagnosis.