First-trimester prenatal diagnosis of Roberts syndrome

We present a case of prenatal detection of premature centromere separation on chorionic villi sampled at 8 weeks' gestation from a woman at risk of recurrence of Roberts syndrome. The same cytogenetic characteristic was confirmed on amniocytes at 14 weeks when ultrasound examination showed morphological anomalies of the fetus. To our knowledge, this is the first report of early prenatal diagnosis of Roberts syndrome.     

Second trimester prenatal diagnosis of the Jarcho-Levin syndrome

The Jarche–Levin syndrome (spondylothoracic dysostosis) is a rare autosomal recessive disorder characterized by a short neck, short trunk and a constricted thorax due to multiple rib and vertebral defects; other visceral malformations are occasionally present. Most cases die in infancy due to respiratory failure. In this report we describe two cases in one family from the United Kingdom. Prenatal diagnosis by ultrasound examination during the second trimester was successfully accomplished in the second case.     

Early prenatal diagnosis of A lethal syndrome of multiple congenital contractures

An ultrasonic diagnosis of a lethal, autosomally recessive syndrome of multiple congenital contractures was made in seven high-risk pregnancies on the 13rd to 17th gestational weeks. The diagnostic findings were the development of progressive subcutaneous oedema from the 13th gestational week on and the decrease of fetal limb movements.     

The prenatal diagnosis of joubert's syndrome of familial agenesis of the cerebellar vermis

The prenatal diagnosis by ultrasound examination of Joubert's syndrome of familial agenesis of the cerebellar vermis is described allowing termination of pregnancy ai 26 weeks gestation. The diagnosis was made by a comparison of the prenatal ultrasound examination with computerized axial tomography obtained from the siblings with the same condition.     

Early prenatal diagnosis of genetic microcephaly

We report a new case of prenatal diagnosis of recessive microcephaly by ultrasound examination allowing termination of pregnancy at 25 weeks gestation.     

A further prenatal diagnosis of mosaic tetrasomy 12p (Pallister-Killian syndrome)

A case of mosaic tetrasomy 12p was detected in amniotic fluid cell cultures from a 28-year-old woman referred to us at 26 weeks' gestation because of hydramnios. The fetus was shown on ultrasonography to have an omphalocele and a short femur length. Labour was induced at 32 weeks. An infant with multiple congenital anomalies was delivered and died after 10 min. The diagnosis of i(12p) or Pallister-Killian syndrome was confirmed cytogenetically in fibroblast and lymphocyte cultures. Increased LDH-B activity was demonstrated in fibroblasts.     

Ring 19 mosaicism detected during prenatal diagnosis

A ring chromosome 19 was found in 14 of 20 metaphases (67 per cent) derived from amniotic fluid cell cultures following amniocentesis because of increased maternal age. Elective termination of the pregnancy revealed a hypotrophic female fetus with mild dysmorphic signs, but no congenital malformations. The case is discussed in relation to three reports in the literature of ring chromosome 19 mosaicism in a phenotypically normal girl, a mentally retarded man, and a boy with normal psychomotor development and minor dysmorphic features.     

Prenatal diagnosis of the fragile-X in male monozygotic twins: Discordant expression of the fragile site in amniocytes

A prenatal diagnosis of the fragile-X syndrome in monozygotic male twins is reported. The expression of the fragile site was discordant in amniotic cells. Fetal blood and, after therapeutic abortion, skin fibroblasts were positive in both fetuses. Our data suggest that great care should be taken when using amniocytes for prenatal diagnosis of the fragile-X syndrome.     

Results from a reference laboratory for prenatal diagnosis of sickle cell disorders in Cuba

A nationwide programme for the prevention of sickle cell (SS and SC) disorders was initiated in Cuba in 1983. Couples at risk were identified by screening pregnant women and the partners of those who carry an abnormal haemoglobin, followed by genetic counselling and the offer of prenatal diagnosis. Prenatal diagnosis was performed in one laboratory, which had carried out 1068 prenatal tests for Hb SS and SC disorders by the end of 1992. The centralization of the service has permitted rapid identification and resolution of problems.     

Early prenatal diagnosis of congenital hypophosphatasia: Case report

Congenital hypophosphatasia is an autosomal recessive disorder, which usually has a fatal outcome during the neonatal period. This report presents the prenatal diagnosis of hypophosphatasia at 16 weeks of gestation. The characteristic ultrasonic findings in this abnormality demonstrate the superiority of ultrasound as compared with radiography.     

Congenital hereditary hypothyroidism—prenatal diagnosis and treatment

Intrauterine diagnosis of congenital hypothyroidism was established on the basis of TSH concentration in amniotic fluid in the 22nd week of gestation for the offspring of a couple both known to have an iodide organification defect. Prenatal treatment consisted of intramniotic injections of 500 meg Na-1-thyroxine, which was administered from the first amniocentesis until one week before delivery. Following delivery, the diagnosis was confirmed by the elevated level of TSH, 60-5 uU/ml, and a gradual decrease of fT4 to 0·8 ng/ml. Regular substitution therapy was commenced on the third day of life. The normal shape and location of the thyroid gland was demonstrated by Technetium scintiscan. At 18 months the infant revealed no significant deviation from normalcy in growth or mental capacity. This experience indicates that testing of amniotic fluid for TSH in the 22nd week of gestation can be diagnostic for congenital primary hypothyroidism. Furthermore, it is suggested that the treatment approach described is warranted in all cases in which there is a high risk of congenital primary hypothyroidism.     

Carrier detection and prenatal diagnosis in Norrie disease

We report the use of DNA probes to determine carrier status in three young women from a large kindred with Norrie disease. One of the women requested prenatal diagnosis during pregnancy. In this pedigree, Norrie disease was not characterized by a deletion at DXS7.     

First-trimester prenatal diagnosis of severe alpha-thalassemia

By means of chorion biopsy together with restriction endonuclease analysis of fetal DNA, first trimester diagnoses were successfully made in 33 fetuses at risk for Bart's hydrops fetalis. Seven pregnancies with Hb H or hydrops fetalis were therapeutically terminated before 4 months of gestation. Of the 26 pregnancies intended to continue, 18 have come to term with normal deliveries; one with threatened abortion was terminated at the end of the first trimester and, seven are progresssing normally.     

False non-paternity in a family for prenatal diagnosis of β-thalassaemia

Initial screening for the common β-thalassaemia mutations with allele-specific oligonucleo-tide probes in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified β gene, was a codon 43 nonsense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for β-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this ‘artefact’ of false non-paternity is worth noting.     

Experience with first trimester prenatal diagnosis of Menkes disease

We have performed 28 first trimester diagnoses for Menkes disease in 27 high risk pregnancies by direct copper measurement on chorionic villi (c.v.) Two male fetuses were found to be affected because of significantly increased copper content. In one male fetus a slightly increased copper content was observed indicating an exogenous copper contamination of the sample. This view was supported by normal results observed after abortion. Three out of 15 diagnostic c.v. samples with a female karyotype showed increased copper levels. In two of these cases, part of the copper content might have been released from the cannulae used for these particular biopsies. Histochemical visualization of copper accumulation in fixed chorionic villi of two affected fetuses and one female fetus was observed. [⁶⁴Cu]-uptake studies have been performed on 11 diagnostic and 10 control c.v. samples. As the control samples in some cases were found to incorporate more [⁶⁴Cu] than the corresponding diagnostic sample, this method cannot at present be used for diagnosis. Compiled results on newborn females gave evidence that two carriers expressed the paternal X-chromosome, and two carriers expressed the maternal X-chromosome in chorionic villi.     

Early prenatal diagnosis of the fragile site AT Xq27.3 associated with Martin-Bell syndrome

Early prenatal diagnosis of the fragile X was attempted in 44 pregnancies, including one twin pregnancy at risk of Martin-Bell (MB) syndrome. The sex ratio was 24M:21F. The fragile site was reproducibly demonstrated in cultured chorionic villus (CV) cells in eight male and five female fetuses. Six of the male and three of the female fetuses were terminated. Simultaneous RFLP analysis provided confirmative data with flanking DNA markers in 3 of 13 analysed cases. Recombination and/or non-informativeness at available distal and/or proximal loci were found in nine cases. In one male fetus, discordance between the haplotype and cyto-genetics (fragile-X-negative) suggested the presence of a normal male transmitter, a double meiotic cross-over within the region, or a false-negative cytogenetic diagnosis. However, discordance between prenatal and post-termination/postnatal cytogenetic findings was not observed in this series. The use of excess thymidine for induction of the fragile X in cultured CV cells provided in the majority of cases a safe and rapid method for cytogenetic diagnosis, with options for early induced termination in fragile-X-positive pregnancies, for simultaneous RFLP analysis, and for subsequent second-trimester analysis of fetal blood in complicated cases.     

The prenatal diagnosis of transient cysts of the fetal choroid plexus

Ultrasound scanning during the second trimester of pregnancy revealed cysts of the choroid plexus in the posterior horn of the lateral ventricle in five cases. All disappeared spontaneously between 20 and 23 weeks and normal infants were subsequently delivered.     

Diagnosis of polyhydramnios in early gestation: Indication for prenatal diagnosis?

Previously published reports have indicated that idiopathic polyhydramnios may be associated with trisomies 18 and 21 and that chromosomal analysis is indicated. Furthermore, the natural history and fetal outcome of polyhydramnios diagnosed in early gestation have not been well delineated. We identified 138 pregnancies with polyhydramnios prior to 26 weeks' gestation. Of 131 complete cases, 21 were diagnosed as severe, 18 as moderate, and 92 as mild polyhydramnios. Congenital abnormalities were noted in 18 of 21 severe cases (86 per cent). Two of the remaining three cases were twin-to-twin transfusion. Thirteen of 18 cases with moderate polyhydramnios (72 per cent) were associated with anomalies; six of the remaining cases were twin-to-twin transfusion. Sixteen of 92 cases of mild polyhydramnios (17 per cent) were associated with congenital abnormalities. In 69 of 76 cases of mild hydramnios not associated with anomalies (91 per cent), the hydramnios resolved prior to delivery. Only 2 of 16 (13 per cent) associated with anomalies resolved. In 4 of 5 cases (80 per cent) with moderate hydramnios and no anomalies, the amniotic fluid volume was normal on subsequent ultrasound. No case of moderate polyhydramnios associated with anomalies or maternal conditions nor any case of severe polyhydramnios resolved. There were seven cases of chromosomal abnormalities in this series; all were associated with sonographic findings in addition to the presence of polyhydramnios. On the basis of these data, we doubt the benefit of amniocentesis following the early diagnosis of idiopathic polyhydramnios in the absence of other ultrasound findings.     

Glycine/serine ratio and the prenatal diagnosis of non-ketotic hyperglycinaemia

We describe our experience of prenatal diagnosis of non-ketotic hyperglycinaemia in four at-risk pregnancies using the glycine/serine ratio in amniotic fluid obtained between 18 and 20 weeks of gestation. All glycine levels were in the normal range. Serine levels were normal in two patients and borderline in the others. Glycine/serine ratios were normal in two patients, moderately increased in one patient ( + 3 SD), and highly increased in one patient ( + 8 SD). All the children were perfectly normal at birth. Because of this false-positive prediction and the false-negative prediction recently reported, we suggest that this unreliable method should not be used.