Prenatal diagnosis of familial ring 21 chromosome

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX, – 21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non-mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.     

A fetus with a chromosome 13 ring and placenta with chromosome 13 rod/ring mosaicism

A fetus was identified by prenatal cytogenetic diagnosis as having a karyotype 46,XY,r(13) (p11q13). Termination of the pregnancy yielded a severely malformed fetus. Fetal abnormalities included anencephaly, imperforate anus and urethral meatus, severe talipes, syndactyly, cardiac defects and other anomalies. Confirmatory studies on cultured placental villi cells indicated a second cell line, 46,XY, −13,+ 13qter→cen::13ql3→qter. This cell line was not detectable in cells derived from the fetus despite extensive studies. It seems likely that the two cell lines arose simultaneously with selection favouring the 46,XY,r(13) line. How the chromosome rearrangements may have arisen is discussed. We are unaware of other cases where a cell line identifiable by a chromosome abnormality appeared to be confined to placental tissue. However, studies on placental tissue may be helpful in understanding the origin of other unbalanced de novo rearrangements.     

Prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in situ hybridization

Cytogenetic studies of cultured amniocytes demonstrated a karyotype of 46, XX/47, XX,+mar. A bisatellited, dicentric, distamycin-DAPI negative, NOR-positive marker was present in 76 per cent of the metaphases examined. Similar markers have been associated with cat eye syndrome (CES). We report on the utilization of fluorescence in situ hybridization (FISH) with a 14/22 a-satellite probe and a chromosome 22-specific cosmid for locus D22S9 to determine the origin of the prenatally detected supernumerary marker chromosome. FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information.     

Prenatal diagnosis of monosomy 18 and ring chromosome 18 mosaicism

The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation.     

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 chromosome mosaicism

The frequency of mosaicism and pseudomosaicism in the prenatal diagnosis of cytogenetic disorders is reported, based on 3000 pregnancies studied in our laboratory. Diagnosis of true mosaicism was only made when an abnomality was detected in two or more independent cultures established from an amniotic fluid sample. On this basis, 0.37 per cent of all cases were diagnosed as true mosaics. 1.07 per cent of all cases had pseudomosaicism involving more than one cell from the same culture with an identical abnormality. 4.13 per cent of cases had a single abnormal cell with an extra chromosome, loss of a sex chromosome (or part of a sex chromosome), or translocation. Details of the outcome and follow-up of cases is given. Particularly problematical were cases where multiple cells from one culture contained an abnormality which could have been clinically significant. A crude estimate of the extent to which true mosaicism might currently be misinterpreted as pseudomosaicism or entirely missed has been made, based on data from the U.S. survey (Hsu and Perlis, in press). It was concluded that even when two, and if necessary a third culture is extensively analysed with an average of 24 cells per culture counted, at least 4.5 per cent of cases of true mosaicism may be completely missed and at least 7 per cent could be misdiagnosed as pseudomosaicism. There is an urgent need for improved laboratory techniques which allow growth of a greater number of cell colonies and therefore a more broadly based analysis. Detailed long term follow-up of prenatally diagnosed mosaics is also essential for assessing the clinical significance of the laboratory findings.     

Prenatal diagnosis of 46, XX/47, XXY mosaicism: A case report

A case of 46,XX/47,XXY mosaicism was diagnosed at 22 gestational weeks by amniocentesis and fetal blood sampling. After genetic counselling, the couple elected to have the pregnancy terminated. Culture of the fetal skin and both gonads confirmed the prenatal diagnosis. In external appearance, the abortus had no remarkable findings except hypospadia. Histology of both gonads showed testicular tissue without evidence of ovarian components.     

Prenatal ultrasound diagnosis of amelia

Amelia is a very rare form of limb reduction defect. The incidence of isolated amelia with or without other limb reductions is 0.4 per 100 000 births. We report a cluster of three cases diagnosed prenatally. One was isolated tri-amelia and two were isolated tetra-amelia.     

Prenatal ultrasound diagnosis of Apert's syndrome

A mother affected with Apert's syndrome was diagnosed by ultrasound scan at 16–17 weeks to have a fetus similarly affected. The typical features of acrocephaly and symmetrical syndactyly were seen. This is probably the first time that this condition has been diagnosed at such a gestation by ultrasound scan. The patient decided to continue the pregnancy, and intrauterine death occurred at 34 weeks. The diagnosis was confirmed by pathological examination.     

Prenatal diagnosis of spinal muscular atrophy in Russia

Ninety-two families with spinal muscular atrophy (SMA) applied for genetic counselling and further prenatal diagnosis. To minimize expenses, only one tightly linked informative marker was determined in the course of preliminary examination, and non-radioactive allele detection was preferably used. Four prenatal diagnoses of SMA type I, four of SMA type II, and one of SMA type III were made. This trial programme shows the considerable requirements, importance, and potential effectiveness of prenatal prediction of SMA in Russia.     

Prenatal molecular diagnosis of gaucher disease

Prenatal diagnosis of Gaucher disease, the most prevalent glycolipid storage disease, is based on a reliable enzyme assay of cells from amniocentesis or chorionic villous samples. However, this method cannot differentiate among the various forms of the disease. This report details four cases of prenatal diagnosis of Gaucher disease, three of which predate the use of molecular diagnosis. DNA mutation analysis to determine the genotype was predictive of the phenotypic status of the fetus and conformed to the genotype of an affected proband where available.     

Prenatal diagnosis of glutathione synthase deficiency

Prenatal diagnosis for glutathione synthase (EC 6·3.2·3) deficiency in two pregnancies of an at-risk couple was performed on amniotic fluid taken at 16 weeks' gestation. 5-Oxoproline (pyroglutamic acid) levels were 970 and 790 μmol/l compared with the normal mean value of 29 μmol/l (range 13–51 μmol/l). The pregnancies were terminated and the diagnosis in one case was subsequently confirmed by assay of glutathione synthase in cultured fetal fibroblasts. In the other, post-mortem tissue samples failed to grow.     

“Prenatal diagnosis of mosaic ring chromosome 13 with anencephaly” in Prenatal Diagnosis 21(2), 102-105

The original article to which this Erratum refers was published in Prenatal Diagnosis 21(2) 2001, 102–105.     

Prenatal diagnosis with biotinylated chromosome specific probes

We have used a Y-chromosome specific DNA probe in a controlled study to determine the presence of Y-chromosome material and to detect numerical abnormalities in uncultured amniotic fluid cells by fluorescent hybridization. Using this non-radioactive method, we correctly predicted fetal sex within 48 h in all but 3 of 54 cases and identified an XYY syndrome. The technique was previously tested with no false-positive or false-negative results on cultured interphase or metaphase nuclei of fetal fibroblasts and adult T-lymphocytes. Fluorescent in situ hybridization was applied to long-term fixed cytogenetic preparations up to 44 months old and was shown to be reliable.     

Prenatal diagnosis and long survival of Fryns' syndrome

We report on a case of Fryns' syndrome diagnosed prenatally in a woman with no family history of this disorder. A computerized database was used for the differential diagnosis. Intensive perinatal care resulted in prolonged survival, which is unusual in individuals with Fryns' syndrome. This case provides further delineation of the developmental course in patients with this condition.     

Prenatal diagnosis of Freeman–Sheldon syndrome (whistling face)

The diagnosis of Freeman–Sheldon syndrome was made by ultrasonographic evaluation of a 20-week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth.     

Prenatal detection of multiple copies of a familial supernumerary marker chromosome

Direct preparations and long-term cultures from a chorion villus biopsy, taken because of a known maternal additional marker chromosome, showed a 48,XX,+mar,+mar karyotype in all cells examined. The same karyotype was revealed in a subsequent amniotic fluid sample and in cord blood at delivery. Detailed examination of the child at delivery and at 1 year of age showed no evidence of phenotypic abnormality or developmental problems.