Prenatal diagnosis of X-linked hydrocephalus in a Chinese family with four successive affected pregnancies

We report on a woman with four successive pregnancies affected with X-linked hydrocephalus (XLH). The first child had prenatal craniocentesis and died in utero. The second child had a postnatal shunting operation, but suffers from severe growth and mental retardation at 5 years of age. In the third pregnancy, prenatal ultrasound detected hydrocephalus at the 16th and 20th weeks of gestation and the pregnancy was terminated. In the fourth pregnancy, ultrasound scanning at the 17th and 20th weeks of gestation revealed no remarkable findings, but hydrocephalus was detected at the 24th week. Autopsy confirmed the prenatal diagnosis. DNA polymorphism analysis of the Bell site of exons 17–18 of factor VIII gene of the woman and her last two fetuses seemed to be compatible with a linkage between the XLH locus and factor VIII gene. Although XLH has a variable presentation of ventriculomegaly, ultrasound scanning is still a useful tool for prenatal diagnosis at present. Earlier and more accurate prenatal diagnosis will be feasible with molecular analysis of the XLH locus or its flanking regions.     

Prenatal diagnosis of the hurler syndrome: Report on 40 pregnancies at risk

In 40 pregnancies at risk for the Hurler syndrome 13 affected fetuses were detected by the demonstration of an α-L -iduronidase deficiency and an increased level of ³⁵S-sulphate incorporation. The diagnoses were confirmed by the analysis of fetal tissues and/or cultured fetal skin fibroblasts. Microassays for α-L -iduronidase, using phenyl α-L -iduronide and more recently 4–methyl-umbelliferyl α-L -iduronide, enabled a reliable diagnosis to be made within 15 to 18 days after amniocentesis. ³⁵S-sulphate incorporation has been a valuable adjunct in cases with a low (heterozygote) enzyme activity.     

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: The diagnostic role of prenatal ultrasonography

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alpha- fetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed.     

Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome

An Erratum has been published for this article in Prenatal Diagnosis 21(7) 2001, 605. Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n=6), amniotic fluid (AF, n=176) and/or fetal blood specimens (n=80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV-specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n=24) or in urine of neonates within the first 2 weeks of life (n=33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live-born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV-DNA and CMV-specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV-DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22–23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p=0.0224). However, normal ultrasound of infected fetuses at WG 22–23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of Joubert syndrome: a case report

Joubert syndrome is a rare, autosomal recessive condition, first described by Joubert in 1969. We present a case of Joubert syndrome from a consanguineous family in which, apart from the cerebellar vermis agenesis, ventriculomegaly, bilateral postaxial polydactyly of hands and right foot and micropenis, episodes of fetal breathing pattern with an increased respiratory rate were also demonstrated by prenatal ultrasound scan. At birth the infant showed an odd face and bilateral fleshy nodules of the tongue. He had an abnormal breathing pattern of alternating tachypnea and apnea. Cranial MRI showed molar tooth sign, hydrocephalus and Dandy–Walker malformation. He had nystagmus, and electroretinography showed retinal dystrophy. Copyright © 2002 John Wiley & Sons, Ltd.     

Comparative study of 15 lysosomal enzymes in chorionic villi and cultured amniotic fluid cells. Early prenatal diagnosis in seven pregnancies at risk for lysosomal storage diseases

A large number of chorionic villi samples obtained from women undergoing elective first trimester termination of pregnancy was analysed by enzyme assays similar to those applied to cultured amniotic cells. The levels of 15 lysosomal enzymes were compared to those observed in tissue cultures of amniotic cells obtained through amniocentesis at 16-18 weeks of pregnancy and the results were discussed in order to assess the usefulness of trophoblast biopsy for first trimester diagnosis of hereditary lysosomal diseases. The data suggest the applicability of this source of fetal cells for prenatal diagnosis of fifteen respective genetically determined enzyme deficiencies with the probable exception of α-L -iduronidase deficiency. Enzyme determinations were performed on chorionic villi samples of two pregnancies at risk for Tay-Sachs disease, three pregnancies for GM₁ gangliosidosis type 1, one for mucopolysaccharidosis type VI and one for Wolman's disease.     

Prenatal diagnosis of extrahepatic biliary duct atresia

A rare case of extrahepatic biliary atresia was diagnosed by a combination of prenatal ultrasound and measurements of fetal digestive enzymes in amniotic fluid. Ultrasound at 15 and 18 weeks' gestation failed to detect the gall bladder, and amniotic fluid digestive enzyme values were below the fifth percentile. The patient decided to terminate the pregnancy. Post-abortal pathological examination confirmed the diagnosis. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of metatropic dwarfism

We present a case of prenatal diagnosis of severe metatropic dysplasia at 20 weeks' gestation. The characteristic prenatal features of this rare autosomal recessive chondrodysplasia appear to be significant dwarfism with an enlarged head and a narrow thorax associated with enlargement of the hands and feet, and the radiographic ‘dumb-bell’ appearance of the long bones.     

Prenatal diagnosis of congenital toxoplasmosis

Ninety-three pregnant women with Toxoplasma gondii seroconversion during pregnancy underwent prenatal diagnosis of fetal toxoplasmosis. The following tests were used: (1) amniocentesis for mouse inoculation (93 subjects), (2) amplification of T. gondii DNA by polymerase chain reaction (PCR) (79 subjects), and (3) cordocentesis for the detection of T. gondii-specific IgM antibodies (13 subjects). All patients had serial ultrasonographic scans to detect those fetuses with abnormalities that could be associated with congenital toxoplasmosis. Eighteen pregnancies (19.4%) had evidence of vertical transmission. A total of 11/18 (61.1%) had positive amniotic mouse inoculation test, while 10/12 (83.3%) had positive PCR results. The combination of both tests allowed the prenatal diagnosis in 17/18 infected fetuses (94.4%). All patients who underwent cordocentesis for the detection of T. gondii-specific IgM antibodies had negative results. However, in two of the above cases fetal toxoplasmosis was detected by amniotic fluid studies. In five of the infected fetuses there were abnormal ultrasonographic findings. All pregnancies with evidence of vertical transmission were terminated, whereas the remaining pregnancies proceeded normally to term. The present data showed that amniotic fluid studies, preferably PCR amplification of T. gondii DNA, are the best diagnostic tools for the detection of vertical transmission in pregnancies with seroconversion during pregnancy. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of cystic fibrosis: I. Prospective study of 51 pregnancies

A prenatal diagnosis was performed in 51 pregnancies with a 1-in-4 risk of having a child with cystic fibrosis. The criteria for determining an affected fetus were based on the results of alkaline phosphatase (ALP) residual activity after inhibition by phenylalanine and by homoarginine, of total ALP activity, and of gamma-glutamyltranspeptidase (GGTP) activity in the amniotic fluid taken between 16 and 19 weeks of pregnancy. The chromosomal analysis of amniotic fluid cells showed trisomy 13 in one case which was excluded from the analysis of biochemical assays. The biochemical assays were in the normal ranges in the amniotic fluid of 35 pregnancies: 26 have reached term and a normal infant has been born, 9 are still in progress. A deficiency of the ALP phenylalanine-inhibitable form, depressed values of total ALP and GGTP were observed in the amniotic fluid of 15 pregnancies: one pregnancy went to term and the infant had CF, in 14 cases the pregnancy was terminated, and meconium ileus was observed in ten of these cases. It was observed that the changes towards abnormal values became more significant with advancing gestational age and that 18 weeks appeared to be the optimum time for diagnostic amniocentesis.