Prospective risk in reciprocal translocation heterozygotes at amniocentesis as determined by potential chromosome imbalance sizes. Data of the european collaborative prenatal diagnosis centres

The Data of the European Cooperative Prenatal Diagnosis Laboratories (Boué and Gallano, 1984) of 596 prenatal (amniocyte) diagnoses of familial rep was examined as to relationships between balanced/unbalanced result and ascertainment, carrier parent and chromosome imbalance size (percentage haploid autosome length). Each rearrangement was graphed once with actual (unbalanced result) or potential (normal or balanced result) imbalances plotted with trisomy as the ordinate and monosomy as the abscissa. The graphed data was divided into 15 regions, each of 2·0 per cent trisomy and 0·75 per cent monosomy and the rate of unbalanced pregnancies determined for each region. The highest rates of chromosomally unbalanced progeny (excluding regions with inadequate data) were found closest to the origin (i.e. associated with the smallest imbalances) and these were for ascertainment category 1 (previous rep unbalanced child) 22·3 per cent for maternal carriers and 39 per cent for paternal carriers. Overall in pooled data for this ascertainment category (without reference to the imbalance graphs) there were for paternal carriers 28·6 per cent unbalanced pregnancies and for maternal carriers 18·1 per cent. The graphed data, therefore, revealed the higher rates associated with some of the rep with small potential (combined duplication/ deficiency) imbalances. Lesser rates were observed for ascertainment category 2 (carrier parent with a history of recurrent miscarriage) with overall percentages of imbalanced progeny ranging from 2·7 (paternal carriers) to 4·7 (maternal carriers). Again, higher rates were revealed in graphed data for small potential imbalances. All unbalanced results for this group (ascertainment category 2) plotted in the region closest to the origin with rates of 16 per cent (maternal carriers) and 9·5 per cent (paternal carriers) in this region. Remarkably in both ascertainment groups 1 and 2 there was no significant difference in the size of the imbalanced segments for unbalanced progeny. In ascertainment group 1 this was (dup/def; mean ±S.D.): 1·09±0·77/0·47 ± 0·45 and in ascertainment group 2: 1·09 ±0·80/0·66±0·71. From the graphed data which arguably denote viability relationships, a trisomy was approximately 2·7 times as likely to survive until amniocentesis as a monosomy of equivalent size. It is proposed that given further data, risk estimates could be determined for rep heterozygotes using the present approach where empiric data (from the family history or an analysed series of similar rep) is not available.     

Prenatal diagnosis of fragile X in a heterozygous female fetus and postnatal follow-up

An apparently normal female infant was born after the prenatal diagnosis of fragile Xq27×28 present in about 4 per cent of amniocytes. The mildly retarded mother had been found in early pregnancy to be heterozygous for fragile X. The child, now 9 months old. showed about the same level of fragile X expression as her mother. Variations in the proportion of cells with fragile X appeared to be related to cell type and laboratory techniques. The infant's growth and development have been normal. Different techniques to induce or increase the expression of fragile X are discussed.     

Autosomal dominant polycystic kidney disease: Prenatal diagnosis by DNA analysis and sonography at 14 weeks

A pregnant woman affected with autosomal dominant polycystic kidney disease (ADPKD) had a history of an affected fetus, diagnosed by sonography at 29 weeks of pregnancy. The proband's father was also affected. DNA analysis performed on chorionic villi at 11 weeks during a second pregnancy predicted an affected fetus, and sonographic examination at 14 weeks confirmed the diagnosis.     

Fetal curarization for prenatal magnetic resonance imaging

Fetal magnetic resonance (MR) imaging was performed at 33 weeks of gestation for investigation of a posterior fossa abnormality found at ultrasound screening. Fetal movements were abolished by vecuronium injected under ultrasound guidance into the umbilical vein. MR images showed atrophy of the left cerebellar lobe with cisternal dilatation. These were confirmed postnatally by CT scan.     

The oxidation of octanoic acid by cultured amniotic fluid cells: The effect of cell type and passage number

We have measured the rate of oxidation of [1⁻¹⁴C]octanoate in cultured amniotic fluid (AF) cells at various passages and in AF cell lines with different clonal morphology. It is possible that both the passage number and the cell type may influence the outcome of prenatal diagnosis of fatty acid oxidation defects using this technique. We found that there was no significant difference between the three major AF cell types (epithelial, large epithelial, and fibroblast) when analysed at identical passage number but there was a significant reduction in octanoate oxidation in all cell types with increasing passage. For reliable prenatal diagnosis, cell lines of similar low passage number should be used.     

The BOR syndrome and renal agenesis-prenatal diagnosis andfurther clinical delineation

This is the first report of prenatal diagnosis of a fetus with brachio-oto-renal dysplasia (BOR) syndrome with right-sided renal agenesis and severe left hypoplasia. The father of this fetus had malformed external ears, a left-sided preauricular pit and branchial cyst, and bilateral mild to moderate deafness without a demonstrable renal anomaly. This family highlights the variable expressivity seen in the autosomal dominant BOR syndrome, the importance of genetic counselling for families with BOR syndrome, and the aetiologic heterogeneity of renal agenesis.     

Chromosomal abnormalities associated with a single umbilical artery

A single umbilical artery was seen in 10 out of 117 cytogenetically abnormal pregnancies. The abnormal karyotypes found to be associated with a single umbilical artery were trisomy 18 (n = 5), monosomy X (n = 2), triploidy (n = 1), sex chromosome (47,XYY; n = 1) and translocation (46t(X,5)(q13p15); n = 1). With the exception of the translocation case, all cases with a single umbilical artery had anatomical defects which were detectable ultrasonographically. This suggests that a single umbilical artery alone is not an indication for prenatal fetal karyotyping.     

Risk of amniocentesis and laboratory findings in a series of 1500 prenatal diagnoses

The experiences with 1500 midtrimester prenatal diagnoses are reported. Abnormal findings of amniotic fluid investigations led to 43 therapeutic abortions. In ± 30 percent of the chromosome anomalies diagnosed, the significance of the effect on fetal development was inconclusive. The outcomes of all pregnancies except one are known. Fetal loss and perinatal mortality involved 69 cases, 23 (33 percent) of which occurred within three weeks after amniocentesis. In these 23 cases there appeared to be a relationship between the degree of experience of the gynaecologist and fetal loss: 3·7 percent when this experience was limited to a maximum of 10 punctures diminishing to 0·3 percent with an experience of more than 50 punctures. It is concluded that the risk of an abortion due to amniocentesis decreases as the gynaecologist becomes more experienced with the puncture technique.     

Early genetic amniocentesis—4 years' experience

Four hundred and thirty early amniocenteses (EAC) from 10 to 14 weeks' gestation were compared with 300 routine amniocenteses (RAC) from 15 weeks' gestation (control A) and 733 routine amniocenteses from 16 to 18 weeks' gestation (control B) with regard to success rates, various growth parameters, and cytogenetic results. Using both in situ and trypsiniz-ation techniques, the success rate was 99·8 per cent for EAC versus 100 per cent for RAC. The average turn-around time for establishing a diagnosis was 8·4 days in EAC versus 8·3 days in 15 weeks' specimens (n.s.) and 7·7 days in 16 to 18 weeks' specimens (p ≦ 0·0001) for the last 200 samples. The banding quality of early specimens compared favourably with that of controls (both 500–550 bphs) and was much better than that in long-term cultured chorionic villus sampling (CVS) (350–400 bphs). For level I and level II mosaicism, no statistically significant differences were noted between EAC and control group A. Comparing EAC with control group B, a significant increase in the number of numerical and structural single cell aberrations was observed (p ≦ 0·025 and p ≦ 0·001, respectively), whereas for multiple cell aberrations only the increase in numerical aberrations was statistically significant (p ≦ 0·001) (x²-test). Clinical problems arising from the detection of mosaicism were solved in all cases by investigating parallel cultures. It is concluded that early amniocentesis is a reliable procedure which permits prenatal diagnosis of numerical and structural chromosome aberrations to a high standard.     

46,XY/47,XY,+ 17p+ mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy-Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post-axial polydactyly and neuroblastoma-in-situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.