Prenatal diagnosis of cleft lip and palate by ultrasound

Bilateral cleft lip and cleft palate can be diagnosed by ultrasonography prior to 20 weeks of pregnancy. The anomaly produces an abnormal facial profile and, on cross-section, the clefts in the maxilla are demonstrable. The method is illustrated by sonograms from a fetus in which the defect was diagnosed before trisomy 13 became known by karyotyping.     

Prenatal diagnosis of 49,XXXYY

The first prenatally diagnosed case of 49,XXXYY is reported. The pathological findings of the fetus included bilateral clinodactyly, decreased carrying angles (OO), and hypertelorism, slightly low set ears and mildly prominent forehead. A minimum of two independent non- disjunctional events are postulated for this polysomy to arise.     

Prenatal diagnosis of hereditary tyrosinaemia: Measurement of succinylacetone in amniotic fluid

A method is proposed for prenatal diagnosis in pregnancies at risk of hereditary tryosinaemia. Affected fetuses were detected on the basis of the abnormal presence in the amniotic fluid of succinylacetone, a metabolite previously identified in sera and urines of patients suffering from hereditary tyrosinaemia. Our data show that the forty amniotic control samples had no detectable succinylacetone, while succinylacetone was found in three out of the thirteen cases at risk. Following the parents' decision, these three fetuses were aborted. The ten other mothers who brought their pregnancies to term had normal infants. Enzymatic analysis from two of the aborted fetuses' livers revealed an absence or a low activity of fumarylaceto-acetate hydrolase (EC 3.7.1.2) compared with control fetal livers of the same age.     

Prenatal ultrasound detection of humero-radial synostosis in a case of antley-bixler syndrome

The Antley-Bixler syndrome is characterized by multiple skeletal fusions including humero-radial synostosis, anterior bowing of the femora, cardiac and renal malformations and a high incidence of early postnatal lethality. In the pregnancy of a mother who had previously given birth to a child with the Antley-Bixler syndrome, prenatal ultrasound diagnosis was performed at 17 and 20 weeks. Fixed flexion of about 80° in both elbows was seen together with humero-radial synostosis and bowing of the ulnae. The fetus performed jerky cranio-caudal movements in its shoulders, but did not, during five hours of real-time observation, move at all in the elbows. Mild anterior bowing of the femora was also observed. The pregnancy was terminated at 21 weeks, and radiological examination of the female fetus confirmed the above mentioned findings including complete bilateral humero-radial synostosis. She also had cardiac and renal malformations. An ultrasound diagnosis of syndromes which have humero-radial synostosis as one feature is possible. Immobility and flexion in the elbows during a long period is probably the essential diagnostic finding.     

Measurement of cholinesterases in amniotic fluid using a naphthyl acetate as substrate: A possible initial test for prenatal diagnosis of open neural tube defects

A quantitative method for cholinesterases in amniotic fluid using the non-specific substrate α naphthyl acetate and the cholinesterase-specific inhibitor, eserine, is described. This assay was used to test 671 samples of amniotic fluid. The diagnoses for fetal ONTDs, based on the levels of AChE + ChE, were compared with those made for the same samples by the AFP method. Correct diagnoses were made by both methods with amniotic fluid from 35 women carrying fetuses with ONTDs and 631 carrying normal fetuses. There were five false-positive test results for normal fetuses by both methods when the cut-off points were 5 standard deviations above the mean for AFP and above the upper limit of the normal range (7. 5 milliunits) for cholinesterase (AChE + ChE). None of the false-positive samples from either method had the acetylcholinesterase band of activity characteristic of ONTDs after gel electrophoresis. In addition to the above 671 samples, 37 pregnancies with serious fetal abnormalities other than ONTDs were tested. Two were identified by both the AFP and AChE + ChE methods, two more by AFP assay and one other by the AChE + ChE assay.     

Prenatal diagnosis of mucopolysaccharidosis by two-dimensional electrophoresis of amniotic fluid glycosaminoglycans

Amniotic fluid from 72 pregnancies at risk for mucopolysaccharidosis have been analysed for glycosaminoglycans (GAG) by means of two-dimensional electrophoresis. Definite results were obtained in all cases and required only 3 days to report. Of the 66 cases for which GAG analysis was accompanied by enzyme assays on cultured amniotic fluid cells, there was agreement of results in 65. In the one case of disagreement the result of GAG analysis proved to be correct. Fourteen pregnancies were predicted to be affected and the predictions were confirmed by studies on fetal tissues and/or cultured cells, or in one case the birth of an affected infant. Of the 58 pregnancies predicted to be unaffected, 48 have so far gone to term and produced healthy infants. There have been no false negative predictions. The analytical method is simple, rapid, and, in this study, has been found completely reliable for prenatal diagnosis.     

Maternal alphafetoproteln screening by the polypropylene tube immunoradiometric assay on dried blood

The polypropylene tube immunoradiometric assay for alphafetoprotein (AFP) determination was applied to maternal serum along with a radioimmunoassay technique during the second trimester of pregnancy. Blood from pregnant women was collected by finger prick on strips of chromatography paper (Schleicher and Schuell No. 903C) and air dried. A 4·75 mm disc spot was eluted in anti-AFP coated tubes containing 1·0 ml of assay medium. After one hour the medium was vortexed and the tubes washed and counted on a Concept 4^tm (Micro- medic Systems, Horsham, PA.19044). The sensitivity of the technique is about 9 μg/l (35 ng/l in the assay) by the Rodbard formula. The concordance between the dried blood and the serum RIA tests in normal pregnancies was over 90 per cent at the 95th and 97th percentiles. This assay on dried blood spotted on chromatography paper was tested on 1003 patients and proved to be an ideal alternative to whole serum screening techniques: it minimizes sample manipulations and can easily be integrated into an existing newborn screening programme.     

Mucolipidosis type IV: Accumulation of phospholipids and gangliosides in cultured amniotic cells. A tool for prenatal diagnosis

Cultured amniotic fluid cells from two mucolipidosis type IV (MLIV)-affected fetuses demonstrated accumulation of phospholipids and gangliosides when compared with normal controls. Like cultured skin fibroblasts from MLIV patients, cultured amniotic cells from the affected fetuses accumulated primarily lyso phospholipids and this could be demonstrated by radioactive labelling with appropriate precursors, either inorganic phosphate or oleic acid. Furthermore, like cultured skin fibroblasts, there was significant retention of exogenously supplied GDIA ganglioside in the affected amniotic cells. This storage was previously demonstrated to be unique to MLIV and thus can be used at present as a specific procedure for prenatal diagnosis of MLIV.     

Sacrococcygeal teratoma: Prenatal diagnosis with elevated alphafetoprotein and acetylcholinesterase in amniotic fluid

A sacrococcygeal teratoma was suspected by ultrasound examination at 24 weeks gestation. The amniotic fluid alphafetoprotein was markedly elevated, as was maternal serum AFP. Gel electrophoresis of amniotic fluid showed an acetylcholinesterase band. Labour began at 25 weeks gestation and the chromosomally normal male fetus was found to have a sacrococcygeal teratoma equal to three-quarters of the weight of the fetus.     

Trisomy 20 mosaicism in amniotic fluid cells

The significance of trisomy 20 mosaicism in cultured amniotic fluid cells is still confusing. We report a case of amniotic cell normal/trisomy 20 mosaicism diagnosed prenatally. The pregnancy was carried to term and a normal baby girl was delivered. The authors consider that in cases of amniotic fluid cell normal/trisomy 20 mosaicism the termination of pregnancy may not be advised, however, the parents should be fully informed.     

Chemical and biochemical studies in fetuses affected with nieman-pick disease type A

Chemical and biochemical studies were performed on two unrelated fetuses affected with Niemann-Pick disease type A, following abortion at about the 19th week of gestation. Abortion was performed as a consequence of previous findings, in amniotic fluid cell cultures, that sphingomyelinase activity was completely absent. Phospholipid analyses of various organs of the fetuses, spleen and liver were the organs mostly affected. Interestingly enough considerable accumulation of sphingomyelin was found in the placenta. The brain was the only organ in which sphingomyeiin storage could not be proved. In addition to sphingomyelin a slight accumulation of cholesterol was noticed. Deficiency of sphingomyelinase activity measured at pH 5·0 was the general characteristic of the affected tissues. It is concluded that the accumulation of sphingomyelin in various organs throughout the body of fetuses affected with Niemann-Pick disease is suggestive of the essential role of the enzyme sphingomyelinase and its biochemical maturation, even during the early stages of gestation.     

Prenatal diagnosis of campomelic dysplasia by ultrasonography

Consanguineous partners had a boy with campomelic dysplasia who died of increasing respiratory distress soon after birth. The next pregnancy was monitored frequently by ultrasonography and a healthy male infant was born at term. During a further pregnancy, ultrasonography suggested campomelic dysplasia in the 16th week of gestation. This was confirmed in the 18th week. The pregnancy was terminated and the fetus showed the typical radiological, anatomical and histological findings.     

Prenatal diagnosis in Canada — 1990: A review

This paper presents the results of a detailed study of the genetic prenatal diagnostic services available in Canada in 1990. All 22 genetic centres offering prenatal diagnostic services as well as the 64 laboratories processing samples were surveyed. Data were collected from each to determine what testing was being done, how many women were being tested, for what conditions, and with what outcomes. Also, data on the 35 formal outreach sites were collected. The statistics presented are for the 1990 calendar year. This survey was conducted for the Canadian Royal Commission on New Reproductive Technologies.     

Prenatal diagnosis of β thalassaemia by reverse phase HPLC

Reverse phase HPLC of radioactive globin chains has been compared to classical carboxy methyl cellulose chromatography for the prenatal diagnosis of β thalassaemia. The two methods correlated highly (r = 0.97 p < 0.0005) and provided an identical diagnosis for 40 fetal blood samples of fetuses homozygous or heterozygous for β thalassaemia. The HPLC procedure was much faster and required fewer biochemical steps (no globin preparation). It was at least as accurate and more sensitive than the classical chromatography. A single column can be used for 150 analyses and is always ready to be used. Last but not least it is much less expensive than CMC chromatography.     

Prenatal diagnosis of exencephaly

This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.     

Prenatal diagnosis of PIBIDS

In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6–12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2–13.5 per cent of residual activity.     

Prenatal diagnosis of hypochondroplasia

Prenatal diagnosis of a fetus at risk for hypochondroplasia, a short limb dwarfism condition similar to achondroplasia, was performed by ultrasound at 22 weeks' gestation. The limb bones were measured and shown to be decreased in length. The pregnancy was terminated. Post abortion X-ray did not show caudal narrowing in the lumbar spine but the pelvis had the features of hypochondroplasia.     

Women's experiences with second trimester prenatal diagnosis

By means of questionnaires, 100 women were asked for their experiences concerning prenatal diagnosis. At four standardized stages of the pregnancy a questionnaire was filled in asking for: expectation, knowledge, attitude towards termination of the pregnancy in case of abnormal findings, reactions to the counselling and the obstetric treatment, interpretation of own risk, experiences since the normal test results were known and ideas to improve the treatment. With regard to the effect of pre-amniocentesis counselling it is concluded that the counselling had little impact on decision making; the counselling caused an increase of factual knowledge: somewhat more than half of the women who did not give a correct answer before counselling, indicated the right answer some time afterwards. Presumed differences in reaction patterns for a number of characteristics were not affirmed by the study; the reactions during the procedure of prenatal diagnosis seem to be highly individual and difficult to predict. In addition to the reactions of the 100 women described in this study, the responses to the first questionnaire of another 16 patients, declining amniocentesis after counselling, are presented.     

Prenatal diagnosis of chromosome mosaicism

The frequency of mosaicism and pseudomosaicism in the prenatal diagnosis of cytogenetic disorders is reported, based on 3000 pregnancies studied in our laboratory. Diagnosis of true mosaicism was only made when an abnomality was detected in two or more independent cultures established from an amniotic fluid sample. On this basis, 0.37 per cent of all cases were diagnosed as true mosaics. 1.07 per cent of all cases had pseudomosaicism involving more than one cell from the same culture with an identical abnormality. 4.13 per cent of cases had a single abnormal cell with an extra chromosome, loss of a sex chromosome (or part of a sex chromosome), or translocation. Details of the outcome and follow-up of cases is given. Particularly problematical were cases where multiple cells from one culture contained an abnormality which could have been clinically significant. A crude estimate of the extent to which true mosaicism might currently be misinterpreted as pseudomosaicism or entirely missed has been made, based on data from the U.S. survey (Hsu and Perlis, in press). It was concluded that even when two, and if necessary a third culture is extensively analysed with an average of 24 cells per culture counted, at least 4.5 per cent of cases of true mosaicism may be completely missed and at least 7 per cent could be misdiagnosed as pseudomosaicism. There is an urgent need for improved laboratory techniques which allow growth of a greater number of cell colonies and therefore a more broadly based analysis. Detailed long term follow-up of prenatally diagnosed mosaics is also essential for assessing the clinical significance of the laboratory findings.