False-negative prenatal exclusion of Wiskott-Aldrich syndrome by measurement of fetal platelet count and size

The study of the fetal platelet count and size can, according to the literature, be used for the prenatal diagnosis of the Wiskott-Aldrich syndrome (WAS). So far, no affected fetuses have been identified by this method. All pregnancies in which this method had been applied to resulted, as correctly predicted, in the birth of normal children. Here we report on a familial case of WAS where the haematological parameters failed to reveal the affected second child. Hence we assume that the platelet count and size of platelets remain normal in fetuses with WAS to the gestational age of 22 weeks and cannot be used for prenatal diagnosis.     

Repeat maternal serum testing in multiple marker down's syndrome screening programmes

The effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE₃) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent. A multivariate Gaussian model was used to estimate the detection and false-positive rates for different repeat testing policies. A policy of repeat testing those with a high risk of a Down's syndrome term pregnancy given age and marker levels would reduce the false-positive rate but there would also be a reduction in the detection rate. For example, using all three markers and a 1 in 250 cut-off risk, the estimated false-positive rate would fall from 5·3 to 3·8 per cent but the detection rate would decrease from 58 to 55 per cent. A policy of repeating those with either high or borderline risks would produce a modest improvement in screening efficiency. Repeating the 11 per cent with a risk exceeding 1 in 500 yields an estimated false-positive rate of 5·0 per cent and a detection rate of 60 per cent. A policy of selective repeat testing is not recommended as it would not substantially improve screening efficiency. Nonetheless, if a repeat test has been performed, the parameters given in this paper will enable an unbiased estimate of the Down's syndrome risk to be calculated for individual women.     

Prenatal diagnosis and carrier detection in mucopolysaccharidosis type II by mutation analysis. A 47,xxy male heterozygous for a missense point mutation

Identification of iduronate-2-sulphatase (IDS) gene mutations in patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) allows fast and reliable carrier detection and prenatal diagnosis. We describe here three cases of prenatal diagnosis by direct detection of the gene mutation. In addition to two affected male fetuses from two different families, a 47,XXY fetus carrying both the normal and the mutant allele was diagnosed in a third family. The latter pregnancy was carried to term and the child is obviously not affected by MPS II.     

Prenatal diagnosis of Hunter syndrome using fetal plasma

The X-linked Hunter syndrome or mucopolysaccharidosis II was diagnosed in a male fetus by demonstrating a severe deficiency of iduronate 2-sulphate sulphatase activity in fetal plasma obtained by umbilical fetal blood sampling at 23 weeks of pregnancy. The diagnosis was confirmed after termination of pregnancy.     

Pregnancy-associated plasma protein A: A possible marker in the classification and prenatal diagnosis of Cornelia de Lange syndrome

The concentration of human placental lactogen (hPL), pregnancy specific beta-1 glycoprotein (SP-1) and pregnancy-associated plasma protein A (PAPP-A) were analysed in consecutive serum samples from a patient who gave birth to a child with Cornelia de Lange syndrome. HPL and SP-1 were present in normal concentrations from week 20 to week 35 of gestation whereas PAPP-A could not be detected in any of the samples examined. Immunohisto-chemical examination of two placentae from Cornelia de Lange syndrome revealed normal localization of hPL and SP-1 but the absence of PAPP-A from the syncytiotrophoblast. The significance of association between Cornelia de Lange syndrome and compromised synthesis of PAPP-A is discussed.     

Prenatal diagnosis of a new syndrome: Holoprosencephaly with hypokinesia

Markedly decreased fetal activity (akinesia/hypokinesia) is usually readily apparent to experienced mothers, and frequently this concern leads to attempts at prenatal diagnosis. We report prenatal diagnosis of two fetuses with congenital contractures, markedly decreased fetal movement, and microcephaly due to severe holoprosencephaly. Such familial recurrence to phenotypically normal parents suggests a newly recognized autosomal recessive or X-linked syndrome that is readily detectable by prenatal ultrasonography.     

Second-trimester maternal serum screening using alpha-fetoprotein,human chorionic gonadotrophin,and unconjugated oestriol: Experience of a regional programme

Over a 2-year period from January 1991 to December 1992, second-trimester maternal serum screening for Down's syndrome using alpha-fetoprotein (aFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE₃) was made available to five health districts in East Anglia, with a total population of 1·2 million. Amniocentesis was offered when the risk of Down's syndrome at term was 1:200 or greater. 25359 singleton pregnancies were screened, representing an uptake of 77 per cent. The recall rate for the 24 per cent of women who had not had a dating scan prior to the test was 9·4 per cent compared with 3·9 per cent for those who had been scanned (P<0·0005). Seventy-five per cent (36/48) of Down's syndrome pregnancies were detected for a false-positive rate of 4·0 per cent. Twenty-five out of 36 of detected Down's syndrome pregnancies were dated by scan prior to sampling, and in the 11 remaining cases, the dates were confirmed by scan after a high-risk result was obtained. The exclusion of uE₃ from the screening protocol would have reduced the detection rate to 52 per cent (25/48) for the same false-positive rate. Eighty-five per cent of women identified at high risk accepted the offer of an amniocentesis. Other fetal abnormalities detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7), abdominal wall defects (4), and steroid sulphatase deficiency (6).     

The BOR syndrome and renal agenesis-prenatal diagnosis andfurther clinical delineation

This is the first report of prenatal diagnosis of a fetus with brachio-oto-renal dysplasia (BOR) syndrome with right-sided renal agenesis and severe left hypoplasia. The father of this fetus had malformed external ears, a left-sided preauricular pit and branchial cyst, and bilateral mild to moderate deafness without a demonstrable renal anomaly. This family highlights the variable expressivity seen in the autosomal dominant BOR syndrome, the importance of genetic counselling for families with BOR syndrome, and the aetiologic heterogeneity of renal agenesis.     

Spontaneous resolution of a cystic hygroma in a fetus with Turner syndrome

The prenatal detection of a cystic hygroma (CH) in a fetus with a 45,X karyotype is described. The cystic hygroma underwent spontaneous resolution and a healthy baby with Turner syndrome was subsequently born. The implications for genetic counselling are discussed.