Prenatal diagnosis of the Klippel-Trenaunay-Weber syndrome

The Klippel-Trenaunay-Weber syndrome is a complex developmental disorder of the vascular and skeletal systems. While many features of the syndrome are congenital, it has not been diagnosed often before birth. This paper describes a case of Klippel-Trenaunay-Weber syndrome diagnosed at 19 weeks' gestation on the basis of sonographic findings and family history. The clinical variability of the syndrome is emphasized and the importance of family history in differential diagnosis is stressed.     

Cu/Zn superoxide dismutase quantification from fetal erythrocytes—an efficient confirmatory test for Down's syndrome after maternal serum screening and sonographic investigations

An enzyme immunoassay especially designed for the quantification of Cu/Zn superoxide dismutase (SOD) in erythrocytes has been applied to measure the SOD of outcomes with high risk for Down's syndrome. From 148 fetuses SOD was quantified from erythrocytes of umbilical vein blood and related to the number of cells, the content of haemoglobin (Hb), and to the haematocrit (Hc). Comparative studies between the SOD content of erythrocytes from the fetuses and their mothers resulted in similar SOD levels (14.09 ± 1.20 for fetal and 14.48 ± 1.63 for maternal cells) with a 1.84-fold smaller variance for fetal cells. The best differentiation between normal fetuses and fetuses with Down's syndrome resulted from the SOD/cell ratio followed by the SOD/Hb ratio. Fixing a cut-off value from the probability density functions that the method results in a specificity of 99.99 per cent, the sensitivity to detect cases of Down's syndrome was 99.71 per cent for the SOD/cell ratio, 70.92 per cent for the SOD/Hb ratio, and 60.21 per cent for the SOD/Hc ratio. Nine cases with Down's syndrome were correctly diagnosed by the SOD/cell ratio determination. Eight of these were confirmed as free trisomy 21 by karyotype analysis and one was found to be a triploidy. The latter was not detected by the SOD/Hb and SOD/Hc ratios because of the one-third higher content of haemoglobin and the larger volume of the erythrocytes which resulted in ratios within the normal range.     

Amniotic fluid enzymes in pregnancies with trisomy 21

The activities of a range of microvillous enzymes in amniotic fluid from normal pregnancies (n = 213) and those complicated by trisomy 21 (n = 26) were compared in a prospective study. Using a centrifugal analyser, the activities of leucine aminopeptidase (LAP), gamma glutamyl transferase (GGT), aspartate transferase (AST), and isoenzymes of alkaline phosphate (ALP) were measured in amniotic fluid alongside alpha fetoprotein (AFP) levels. Of the markers studied, LAP was found to be the most reliable indicator of trisomy 21. Using levels below the 5th percentile, LAP showed sensitivity 73 per cent, specificity 94 per cent, and predictive value positive 63 percent. Although these tests would not replace karyotyping in all cases, the measurement of LAP could be useful as a rapid initial screening test, particularly when amniocentesis is performed for indications other than chromosomal abnormalities.     

Four-marker serum screening for Down's syndrome

The value of measuring the separate sub-units of human chorionic gonadotrophin (free α-hCG and free β-hCG) instead of total hCG together with alpha-fetoprotein (AFP) and unconjugated oestriol (uE₃) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE₃, free β-hCG, and free α-hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE₃, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four-marker test reduced the false-positive rate by one-third from 3 per cent using the triple test to 2 per cent with the four-marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight. The four-marker test is, both from a medical and from a financial perspective, the most effective method of prenatal screening for Down's syndrome suitable for routine use.     

Prenatal detection of congenital hypospadias in the wolf-hirschhorn (4p —) syndrome

Hypospadias is one of the most prominent and characteristic midline defects in male infants with the Wolf-Hirschhorn (4p —) syndrome. In this report we present a case in which hypospadias was identified prenatally at 29 weeks' gestation in association with intrauterine growth retardation. Cytogenetic evaluation after birth confirmed a 46, XY, del(4)(p14) karyotype. The prenatal identification of hypospadias in fetuses with intrauterine growth retardation and normal amniotic fluid should suggest a diagnosis of Wolf-Hirschhorn syndrome.     

Walker-Warburg syndrome: Prenatal ultrasound findings

The prenatal sonographic findings in a case of Walker-Warburg syndrome are described. The patient was not at risk for this condition. Ultrasound examination at 34 weeks' gestation revealed hydrocephaly, Dandy-Walker anomaly, and striking ocular abnormalities. From a review of the literature it appears that while intracranial abnormalities can lead to the diagnosis in cases at risk for this syndrome, ocular abnormalities are rather characteristic for this syndrome and they should be searched for in every case of hydrocephaly or encephalocele.     

Immunoblot detection of enzyme proteins of peroxisomal β-oxidation in fibroblasts,amniocytes, and chorionic villous cells. Possible marker for prenatal diagnosis of Zellweger's syndrome

The amounts of enzyme proteins of peroxisomal β-oxidation in fibroblasts and chorionic villous cells from infants with Zellweger syndrome and in fibroblasts, amniocytes, and chorionic villi from healthy controls were measured by immunoblot analysis. Immunoreactive proteins of peroxisomal acyl-CoA oxidase and 3-ketoacyl-CoA thiolase were absent in fibroblasts and chorionic villous cells from the patients, yet these enzyme proteins were present in fibroblasts, cultured amniocytes, and chorionic villi from the normal controls. These results show that immunoblot analysis of peroxisomal β-oxidation enzymes in amniocytes and chorionic villous cells is of potential value for the prenatal detection of Zellweger syndrome.     

Prenatal diagnosis of thrombocytopenia absent radius syndrome by ultrasound and cordocentesis

The prenatal diagnosis of thrombocytopenia absent radius (TAR) syndrome, utilizing ultrasound and cordocentesis, is described. To our knowledge, this represents the first prenatal diagnosis of this condition in an index case. The diagnostic evaluation of a fetus with upper extremity limb reduction defects is discussed.     

Prenatal diagnosis of hunter syndrome using chorionic villi

A case of the Hunter syndrome diagnosed prenatally using chorionic villi is presented. Chorion biopsy was performed in the 10th week of pregnancy. The sample was examined for karyotype and for iduronate sulfatase activity. The fetus was male and the enzyme activity reduced to 4 per cent of normal. Termination of pregnancy occurred at the 11th week.     

PRENATAL DIAGNOSIS OF CYSTIC HYGROMA AND CHORIOANGIOMA IN THE WOLF-HIRSCHHORN SYNDROME

We report the prenatal diagnosis of Wolf-Hirschhorn syndrome (4p –) in a 24-week-old fetus. Echographic features included cystic hygroma, a complex heart defect with right ventricular hypoplasia, and a large placental chorioangioma. We suggest that chorioangioma may be associated with chromosomal imbalance and that systematic careful morphologic examination of the fetus and karyotyping of any pregnancy in which large chorioangioma is detected is advisable. Jugular lymphatic obstruction sequence has not been reported so far in association with 4p– syndrome.