First-trimester prenatal diagnosis in couple at risk for homozygous achondroplasia.
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Achondroplasia↗
Biomedical subjects
K J Blakemore
Publications and source records attributed to K J Blakemore.
The use of polymerase chain reaction to determine fetal RhD status.
OBJECTIVE: Our purpose was (1) to establish the accuracy of a deoxyribonucleic acid amplification method in determination of RhD status in adult blood samples, including weak D variants (previously referred to as Du) and a D mosaic, and (2) to apply the method to determine fetal RhD status in alloimmunized pregnancies. STUDY DESIGN: Twenty-five adult blood samples, including five weak D variants and one D mosaic, were analyzed with a polymerase chain reaction to determine RhD type. The method was then applied to amniotic fluid samples obtained by amniocentesis from three RhD-negative women with known RhD sensitization. RESULTS: RhD type determined by polymerase chain reaction for all adult blood samples agreed with serologic typing results. All weak D variants and the D mosaic gave results consistent with RhD positivity. Fetal RhD status was determined in each of the three alloimmunized pregnancies, and obstetric management decisions were made on the basis of these results. CONCLUSIONS: This polymerase chain reaction method allows rapid and accurate determinations of fetal RhD status by amniocentesis. Fetal blood sampling or serial amniocenteses may be avoided when the fetus is RhD negative, and plans for surveillance and intervention can be confidently made if the fetus is RhD positive. However, before the widespread use of this assay, its sensitivity and specificity must be established. Because weak D variants and a D mosaic demonstrated RhD-positive status by polymerase chain reaction, the method described is applicable to these RhD variants.
Adult↗
Unilateral renal hypoplasia and contralateral renal agenesis: a new association with 45,X/46,XY mosaicism.
The association of urinary anomalies with Turner's syndrome is well established. This report describes an unusual antenatal presentation of this cytogenetic disorder and the first reported case of unilateral renal hypoplasia and contralateral renal agenesis in a 45,X/46,XY fetus. The fetus presented with severe third trimester oligohydramnios and symmetrical intrauterine growth retardation at 29 weeks and 2 days' gestation. Chorionic villus cultures revealed a 45,X karyotype. A phenotypically male infant weighing 1833 g was delivered at 35 weeks and 2 days. Chromosomal analysis of the newborn showed a 45,X/46,XY mosaicism, and surgical exploration revealed absence of the left kidney and a hypoplastic right kidney. The infant died at 11 months of age from renal failure and peritonitis. This case demonstrates that monosomy X may be encountered in fetuses with marked growth delay and oligohydramnios. The etiology of the oligohydramnios in this case was a fetal renal malformation not previously described in Turner's syndrome. Antenatal cytogenetic findings should be confirmed postnatally, with a search for mosaicism, when monosomy X is encountered.
Female↗
Osteogenesis imperfecta and campomelic dysplasia: difficulties in prenatal diagnosis.
The classic features of osteogenesis imperfecta and campomelic dysplasia typically are so specific that these two forms of skeletal dysplasia are among the few that can be diagnosed in the second trimester of pregnancy. We report a series of seven examples of osteogenesis imperfecta and one example of campomelic dwarfism to illustrate the difficulty of differentiating these two disorders in utero. The prenatal sonographic findings in three of the osteogenesis imperfecta cases mimicked campomelic dwarfism, whereas the case of campomelic dwarfism was antenatally diagnosed as osteogenesis imperfecta.
Adolescent↗
Basic concepts in molecular (DNA) diagnosis.
There has been an explosion of new information in molecular biology that will change the ways in which we practice medicine in the future. These laboratory advances in disease detection at the DNA level are quickly finding clinical application in prenatal diagnosis. An understanding of some basic concepts of DNA laboratory techniques and their applications is increasingly important in obstetrics and gynecology today.
DNA↗
Fetal blood sampling.
Fetal blood sampling is accepted and widely practiced by experienced perinatologists. Its facile and safe access to the fetal circulation has broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal disease states can now be identified and treated earlier, directly, more quickly, and more effectively than before, resulting in improved patient care. The volume of fetal blood to be retrieved and collection media for blood (Table 7) will be dictated by the indication for the procedure and thus the desired laboratory tests. These items and the preferred sampling site should be planned in advance by the operator. However, a flexible approach to fetal blood sampling should be maintained, anticipating the variability of fetal positions, cord insertions, and ultimate specimen volume. Teamwork among the perinatologist, sonographer, laboratory, and patient will continue to expand the role of fetal blood sampling in obstetrics.
Blood Specimen Collection↗
Prenatal identification of small mosaic markers of different chromosomal origins.
In situ hybridization using a series of alphoid DNA probes has demonstrated the origin of two small accessory mosaic marker chromosomes ascertained from 1079 amniocenteses. These markers appeared to be de novo, derived from acrocentric chromosomes, and identical by traditional cytogenetic staining (G, Q, C, AgNOR, Hoechst-distamycin). Molecular characterization showed that one marker had originated from chromosome 14, the other from chromosome 22. Clinical outcome in both cases was normal.
Adult↗
Fetal ascitic fluid: a new source of lymphocytes for rapid chromosomal analysis.
BACKGROUND: The cells found in ascites can be processed like amniotic fluid for fetal karyotyping. We have characterized these cells and used them for a rapid cytogenetic result. CASES: Three patients presented with massive fetal ascites detected by sonography. Samples of ascitic fluid were obtained at fetal paracentesis. Cells from the fluid were cultured using standard methods for fetal blood, and were compared with fetal blood lymphocytes and amniocytes. The length of time in culture, chromosome morphology, and mitotic index of ascitic fluid cells were equivalent to those of fetal blood. In the third case, we performed immunophenotyping on the ascitic fluid cells. CONCLUSION: Ascitic fluid contains lymphocytes that permit rapid chromosomal analysis within 96 hours.
Adult↗
What can be learned from cordocentesis?
Cordocentesis is a well-accepted procedure that is widely practiced by experienced perinatologists. Its facile and safe access to the fetal circulation has broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal disease states can now be identified and treated earlier, directly, more quickly, and more effectively than before, resulting in improved patient care. Although cordocentesis has been embraced by the perinatal community, it is, by definition, a technique of obtaining a fetal blood sample. A prerequisite for the procedure to exert its full impact on perinatal care is a highly capable clinical laboratory. The facility must be aware of the commonly requested fetal serologic, hematologic, and serum chemistry studies, as well as their normal values. Efforts must be made to perform fetal blood studies rapidly and reliably on small specimens. Laboratory personnel should be familiar with the indications and pitfalls of these tests and those that are best referred to a specialty laboratory. A general understanding of the perinatologist's needs and concerns will lead to a cooperative working relationship between clinician and laboratory. In this manner, we will truly discover what can be learned from cordocentesis.
Blood Specimen Collection↗
Analysis of reciprocal translocations by chromosome painting: applications and limitations of the technique.
Fluorescent in situ hybridization with chromosome-specific DNA libraries (chromosome painting) is an important new method for assessing chromosome rearrangements. In the research presented in this paper, two familial reciprocal translocations have been studied in the balanced and unbalanced forms, using both traditional G-banding techniques and chromosome painting. Although for each case two chromosomes were involved in the rearrangement, we found that only one chromosome library was suitable for detecting the translocation. These findings illustrate both the potential and the limitations of chromosome painting as a diagnostic tool in cytogenetics.
Adult↗
Isolated fetal ascites detected by sonography: an unusual presentation of Turner syndrome.
The prenatal sonographic diagnosis of Turner syndrome usually depends upon the discovery of a cystic hygroma or nonimmune hydrops fetalis. This report describes isolated fetal ascites as a newly recognized presentation of the disorder. Intrapartum fetal paracentesis permitted atraumatic vaginal birth. The etiology of the ascites in this case was congenital intestinal lymphangiectasia, consistent with the generalized lymphatic hypoplasia previously described in Turner syndrome.
Adult↗
The vanishing twin: an explanation for discordance between chorionic villus karyotype and fetal phenotype.
One 'erroneous' diagnosis occurred in 200 first-trimester chorionic villus samples (CVS) analysed. In direct preparations following 24 h incubation as well as in long-term cultures, a 46,XX karyotype was observed in the villi (28 and 25 cells, respectively). At 20 weeks of gestation, labour was induced because of fetal death in utero. An autopsy performed on the fetus revealed a male phenotype. Placenta and fetal tissues were not submitted for cytogenetic studies. The discordant CVS karyotype (46,XX), in view of the male fetal phenotype, prompted further cytogenetic and molecular studies. Chromosome marker studies on the parents' blood and chorionic villi confirmed both maternal and paternal inheritance of chromosomes in the CVS. DNA studies on formalin-fixed skin using a Y-specific probe, DYZ1, confirmed the presence of a Y chromosome in the fetus. The most likely cause of the discrepant CVS karyotype is the presence of an undetected degenerating dizygotic twin.
Adult↗
Transition from normal early pregnancy to blighted ovum.
Four cases of blighted ovum which had normal pregnancies by earlier ultrasound including embryonic heart activity are presented. There was no unique karyotype associated with this phenomenon.
Embryo Loss↗
Counseling in congenital heart defects.
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Genetic Counseling↗
Stuck twin with cotwin nonimmune hydrops: successful treatment by amniocentesis.
Until the recent introduction of therapeutic amniocentesis, pregnancies complicated by the stuck twin phenomenon usually suffered poor outcomes. We report the first case in which a single amniocentesis of the cotwin was followed by equalization of amniotic fluid volume in both sacs, resolution of nonimmune hydrops in the cotwin, and delivery of 2 healthy infants. The cause of the phenomenon in this was most likely severe twin-twin transfusion, based on a negative hematologic and serologic immune and nonimmune hydrops evaluation, and placental histology revealing a superficial large-caliber arteriovenous anastomosis joining the twins' circulations without an intervening capillary bed. The mechanism proposed for the physiologic response in this case to therapeutic amniocentesis is based on the correction of abnormal amniotic fluid volumes and pressures. This contention is supported by histologic evaluation of the placenta and the intrapartum fetal heart rate tracing.
Adult↗
Amniocentesis and chorionic villus sampling.
Amniocentesis and chorionic villus sampling (CVS) remain the most commonly used invasive prenatal diagnostic procedures. Recent reports on early amniocentesis demonstrate its application to the prenatal detection of certain biochemical disorders. However, its role in the evaluation of open fetal defects of the neural tube or ventral wall is still under investigation. The fact that many reports concerning early amniocentesis include a majority of patients beyond 11 to 12 weeks' gestation, thus placing the procedure outside the first trimester, make comparisons with CVS (usually performed between 9 and 11 weeks) problematic. The role of midtrimester amniocentesis in evaluating elevations of maternal serum alpha-fetoprotein, following a normal ultrasonographic examination performed specifically to detect fetal anomalies, is under scrutiny. It appears that risk adjustment may be appropriate following a normal scan, and prior to invasive procedures, but each center's recommendation to a given patient will depend on the expertise of the individual sonographer, as well as the quality of examination. CVS has gained acceptance as a safe first-trimester means of prenatal diagnosis, with increasing applications in the later stages of pregnancy. Chromosomal mosaicism detected by CVS may represent a phenomenon inherent to placental tissue; questions remain regarding mosaicism as a potential marker for increased pregnancy loss. Comparisons between the transcervical and transabdominal routes are reviewed, with equivalent results regarding safety and efficacy. Recent evaluations of fetomaternal transfusion following CVS are also described.
Amniocentesis↗
Sexual discordance in monozygotic twins.
We report on monozygotic (MZ) twins who were discordant for phenotypic sex and Ullrich-Turner syndrome (UTS). The nonviable female was hydropic with cystic hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia, intestinal malrotation, and small ovaries. The male was phenotypically normal. The monochorionic, diamniotic placenta had hydropic changes limited to the UTS infant's side. Skin samples from the infants and blood from their parents were obtained for cytogenetic and molecular analysis. Karyotypes of the twins were 45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8 loci showed complete identity. MZ twins discordant for phenotypic sex have been described previously. Most of these show evidence of mosaicism in a 45,X patient with a normal 46,XY cell line, and a normal 46,XY male. While the issue of mosaicism in our case cannot be fully resolved, no mosaicism was found in 50 cells analyzed cytogenetically from each culture or by PCR analysis of a Y-specific sequence. The twins probably originated from either postzygotic nondisjunction or anaphase lag, followed or accompanied by twinning. The discordant placental morphology suggests an embryonic origin of at least part of the placental mesenchymal core.
Abnormalities, Multiple↗
The significance of trisomy 7 mosaicism in chorionic villus cultures.
Two cases of mosaic trisomy 7 confined to the cultured cells and not found in direct preparation were detected from 200 consecutive first-trimester chorionic villus samples (CVS) analysed. The mosaicism was similar in the two cases, but the pregnancy outcome was different. In both cases, the direct metaphases from the CVS were 46,XY. Culture metaphases were mos46,XY/47,XY, +7; the trisomy 7 was seen in 34 per cent of cells from case 1 and 53 per cent from case 2. A sonogram at 15 1/2 weeks revealed fetal death in utero in case 1, and the patient declined amniocentesis. The fetal tissue failed to grow in culture, but the placental cultured cells were 47,XY, +7 in 28 (100 per cent) cells analysed. In the second case, all the amniotic fluid cells were 46,XY and the pregnancy resulted in a normal male with a 46,XY karyotype in the cord blood and foreskin fibroblast cultures. The term placenta was mosaic with 13/163 (8 per cent) trisomy 7 cells. Extensive cytogenetic studies on the placenta for the first time confirmed trisomy 7 mosaicism confined to the villus cultures.
Adult↗