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.     

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.     

Longitudinal assessment of blood flow velocity waveforms in the healthy human fetus

A longitudinal study was carried out on 30 healthy fetuses in order to assess the modifications of fetal blood flow throughout pregnancy. The pulsatility index was evaluated at two-week intervals by means of pulsed Doppler equipment. In the umbilical artery measurements were performed from 20 weeks onwards, whereas in the descending aorta and internal carotid artery analysis started from 26 weeks onwards. A decrease of the pulsatility index in umbilical artery and in the ratio between the pulsatility indexes in umbilical artery and internal carotid artery was found over the second half of pregnancy.     

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.     

Prenatal diagnosis of aortic atresia by colour doppler flow mapping

A case of aortic atresia with insufficiency of mitral valve diagnosed prenatally at 33 weeks of gestation is presented. An accurate diagnosis of this fetal cardiovascular malformation was possible by application of Doppler colour flow mapping, which demonstrated (a) the absence of forward flow in the hypoplastic ascending aorta, (b) reverse flow of blood from the ductus arteriosus into the severely hypoplastic ascending aorta in the late systole, (c) pansystolic mitral valve regurgitation, and (d) absent flow across the foramen ovale as a result of premature closure of the foramen ovale.     

Prenatal diagnosis of trisomy 9 mosaicism possibly limited to fetal membranes

In repeat amniotic fluid cultures mosaicism due to trisomy 9 was noted. Autopsy of the aborted female fetus showed a sinus urogenitalis and gonadal dysgenesis with absence of germ cells only. Fetal lymphocytes and skin fibroblasts had a normal karyotype but trisomy 9 was found in cells grown from placenta. It is likely that trisomic cells were limited to fetal membranes.     

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.     

Prenatal demonstration of a cervical myelocystocele

Myelocystocele is a rare spinal cord disorder and has not been described prenatally. We report a case in which prenatal ultrasound and magnetic resonance imaging (MRI) demonstrated a posterior cervical mass which was initially thought to be a meningocele or an atypical cystic hygroma. Surgery performed at 1 day of age showed this to be a myelocystocele. Therefore, the differential diagnosis of an extracranial cystic mass in the posterior cervical region should be expanded to include myelocystoceles.