The prenatal diagnosis of the cerebro-hepato-renal syndrome of Zellweger

The prenatal diagnosis of the cerebro-hepato-renal syndrome of Zellweger (CHRS) was made by assaying the levels of very long chain fatty acids (VLCFAs) in amniotic fluid cell cultures, obtained by amniocentesis at 16 1/2 weeks of pregnancy. The family-at-risk, because they had previously borne a child with CHRS, accepted these results as indications of an affected fetus, and chose to terminate the pregnancy at 20 1/2 weeks of gestation. The diagnosis was confirned by the phenotype of the aborted fetus and the presence of markedly elevated levels of VLCFAs in fetal liver homogenates. The prenatal diagnosis of CHRS, which can now readily be determined from amniotic fluid cell cultures, is an important step in genetic counselling of families-at-risk for this disease.     

Antenatal thrombocytopenia in three patients with TAR (thrombocytopenia with absent radii) syndrome

Three fetuses with TAR (thrombocytopenia with absent radii) or TAR variant syndrome were found to be thrombocytopenic during the third trimester of the pregnancy. These findings indicate that fetal blood sampling, besides ultrasonography, skeletal radiographs, or even fetoscopy, may indeed contribute to the prenatal diagnosis of TAR syndrome, and thus may help in differentiating TAR syndrome from other syndromes with malformations of the upper limbs.     

First-trimester diagnosis of Meckel–Gruber syndrome by transabdominal sonography in a low-risk case

Meckel–Gruber syndrome is a rare autosomal recessive disorder often resulting in neonatal death within a few hours of life. The condition is usually diagnosed ultrasonographically in the second trimester and earlier diagnosis has been mainly confined to high recurrence risk pregnancies. We describe the earliest non-invasive diagnosis of this condition at 12⁺² weeks' gestation in a patient with no previous history using transabdominal ultrasound. Pregnancy termination was declined. Subsequent development of anhydramnios in the mid-trimester resulted in poor fetal visualization. We propose that first-trimester diagnosis of this condition is not only possible but preferable, as normal liquor volume facilitates visualization of fetal anatomy.     

First-trimester screening for fetal chromosomal abnormalities. Preliminary results

We have started a multicentre trial to study the possibilities of first-trimester maternal serum screening for fetal chromosomal abnormalities. Maternal blood samples were obtained before 13 weeks of gestation. We present the preliminary results of the first 950 patients on alpha-fetoprotein (AFP). Results on cancer antigen 125 (CA 125) in Down's syndrome and normal pregnancies are also presented. We conclude that the results on AFP are promising and that CA 125 might be predictive for fetal Down's syndrome.     

Maternal serum free α-human chorionic gonadotrophin levels in twin pregnancies: Implications for screening for Down's syndrome

Maternal serum free α-human chorionic gonadotrophin (free α-hCG) levels were determined in twin and singleton pregnancies at 15–22 weeks of gestation using a set of stored serum samples relating to 200 twin pregnancies and 600 singleton control pregnancies matched for gestational age and duration of storage. Free α-hCG values are, on average, 1·66 times greater in twin pregnancies than in singleton pregnancies (95 per cent confidence interval 1·56–1·76). If maternal serum free α-hCG is used in screening for Down's syndrome, values in twin pregnancies can be adjusted using this result so that screening can be performed in twin pregnancies as well as in singleton pregnancies.     

Risk for chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration a european collaborative study on prenatal diagnoses 1981

Based on 2890 prenatal diagnoses from 12 European countries the risk for a chromosomally abnormal fetus at amniocentesis after the birth of a child with a chromosome abnormality has been estimated to be 1.3 per cent when the mother's age is 34 years or less at amniocentesis and 1.8 per cent if the mother is older. This risk does not depend on paternal age, and it is independent of the type of the chromosome abnormality of the index child. Some geographical heterogeneities were detected. Therefore, the overall risk has to be considered as a rough estimate. The chromosome constitution of the abnormal fetus differed from that of the index patient in 21 of 41 cases. Several explanations for the higher risk have been discussed. If the index child had trisomy 18, 13 or a sex chromosome abnormality, the fetus tended to be a female. If the index child was a trisomy 21, the fetal sex ratio was normal.     

Macroglossia: Prenatal ultrasonographic diagnosis and proposed management

A case in which macroglossia was the sole unusual prenatal sonographic finding in a fetus affected with trisomy 21 is presented. The differential diagnosis of fetal macroglossia is given, emphasizing its strong relationship to fetal aneuploidy, together with the principles for evaluation and management.     

Repeat maternal serum testing for down's syndrome screening using multiple markers with special reference to free α and free β-hCG

To determine the effect of routine repeat testing in serum screening for Down's syndrome, we compared estimates of the detection and false-positive rates. Five serum markers were measured-alpha-fetoprotein (AFP), unconjugated oestriol (uE₃), human chorionic gonadotrophin (hCG), and its two subunits, free α and free β-hCG. First and repeat test marker levels were available from 142 women whose samples had been routinely collected and stored in an antenatal serum bank. Different repeat testing policies were compared for various combinations of the markers. If all women had repeat tests using the four markers AFP, uE₃, and free α and free β-hCG, the detection rate for a 5 per cent false-positive rate was 69 per cent compared with 65 per cent if no women were repeated. Policies of repeating selected women gave similar results. The small gain in screening performance with repeat testing performed routinely is not worthwhile. If a woman does happen to have a repeat test, her risk estimate should, however, be based on both results, not just the second.     

Prenatal diagnosis of Pallister–Killian syndrome: Resolution of cytogenetic ambiguity by use of fluorescent in situ hybridization

We report a case of Pallister-Killian syndrome initially diagnosed prenatally as tetrasomy 21. A 33-year-old primiparous woman was noted at 24 weeks' gestation to have moderate polyhydramnios. Ultrasonography showed diminished fetal stomach filling, hydronephrosis, and prominence of the cisterna magna. Cytogenetic analysis of cultured amniocytes was initially interpreted as mosaic tetrasomy 21: 46,XX/47,XX,+i(21q). The patient was then referred to our centre for genetic counselling. At 34 weeks' gestation, a dysmorphic infant was delivered and died within 30 min. Physical features were consistent with the Pallister-Killian syndrome. Renal, gastrointestinal, and central nervous system anomalies were found at post-mortem examination. Analysis of peripheral lymphocytes revealed 5 per cent of cells with a marker chromosome, while 92 per cent of cultured fibroblasts had this same marker. Fluorescent in situ hybridization (FISH) using an alpha-satellite probe for chromosomes 13 and 21 failed to hybridize to the marker, while a chromosome 12 centromeric probe unequivocally identified it as an i(12p). Use of FISH can provide rapid, specific prenatal diagnosis of ambiguous marker chromosomes and improve prenatal counselling.