Trisomy 20 mosaicism in prenatal diagnosis–a review and update

A total of 66 cases with prenatal diagnosis of trisomy 20 mosaicism was reviewed. Since the majority of cases (85 per cent) was associated with grossly normal phenotype and the abnormalities noted in 15 per cent of cases were inconsistent and rather non-specific, no causal relationship between trisomy 20 mosaicism and a specific malformation syndrome can be established. The possiblity of an association between an abnormal phenotype and a high percentage of trisomy 20 cells (> 60 per cent) must be considered preliminary and be viewed with caution. The fact that cells with trisomy 20 have not been recovered from blood cultures and were detected more frequently from specific fetal tissues, (such as kidney, rectum, oesophagus), and from placental tissues, suggests that trisomy 20 is more likely to be confined to certain fetal organs and to extra-embryonic tissues. This review calls for the collection of more data on all cases of trisomy 20 mosaicism diagnosed prenatally, in order to provide more accurate information to the prospective parents.     

A revisit of trisomy 20 mosaicism in prenatal diagnosis—an overview of 103 cases

One hundred and three cases with prenatal diagnosis of trisomy 20 mosaicism through amniocentesis were reviewed. Approximately 90 per cent (90/101) of the cases were associated with grossly normal phenotype. It is likely that, in the majority of cases, cells with trisomy 20 were extraembryonic in origin or largely confined to the placenta. However, in some cases, the cells with trisomy 20 were confined to certain specific fetal organs or tissues such as kidney, skin, etc. Cytogenetic follow-up studies in liveborns should include a culture from urine sediment.     

XX/XY chimerism encountered during prenatal diagnosis

46,XX/46,XY chimerism has previously been reported in patients with abnormal sexual development, and rarely in otherwise normal individuals. We report the first postnatally documented prenatal diagnosis of whole-body 46,XX/46,XY chimerism in humans, discovered by maternal age amniocentesis. The normal male phenotype in this child creates a dilemma in prenatal counselling, since genotypic male/female chimerism cannot be assumed to imply an abnormal sexual phenotype.     

The impact of prenatal diagnosis on the occurrence of chromosome abnormalities

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three-year (1981–1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15·5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis–-either by PND or by clinical diagnosis after birth. For the total population, 7·3 per cent of cases of DS were detected prenatally, and 15·4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index–-the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND–-has potential for widespread use. Queensland data for this ratio is 0·34, a figure consistent with that from other studies. Thus a 3·5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.     

Pericentric inversion of chromosome 19: prenatal diagnosis and genetic counselling

During prenatal diagnosis for advanced maternal age, a pericentric inversion of a chromosome 19 was detected in a male fetus. The inversion was familial, transmitted to the fetus by the phenotypically normal mother. The pregnancy resulted in a term birth of a phenotypically normal male infant. Inversion 19 appears to be a rare abnormality with only seven families reported thus far including ours. Infants with duplication deficiencies for chromosome 19 have not been reported in these families. This may suggest an apparent suppression of crossing over and recombination within the inverted segment of chromosome 19 during meiosis.     

United states survey on chromosome mosaicism and pseudomosaicism in prenatal diagnosis

The survey of the incidence of chromosome mosaicism and pseudomosaicism detected in prenatal diagnosis included data from approximately 60 000 genetic amniocenteses in the United States. There were 59 participating cytogenetic laboratories nationwide. The overall incidence of chromosome mosaicism was 0.25 per cent (range of 0–0.89 per cent). The average frequency of pseudomosaicism involving multiple cells or clones was 0.7 per cent (range of 0–11.21 per cent). The frequency of single cell or clone pseudomosaicism was 2.47 per cent (range of 0–11.49 per cent). In cases of pseudomosaicism with trisomy, the most frequently involved chromosome was number 2; occurrence rates of trisomies 7,X,9,17 and 20 were also relatively high. In cases of pseudomosaicism with structural abnormalities, this survey showed an association between relative chromosome size and the frequency of involvement in structural rearrangement. Data on a total of 185 cases of chromosome mosaicism collected in this survey as well as from other documented sources showed 89 cases involved an autosome, 13 cases a sex chromosome, and 23 a marker chromosome. The frequency of noticeable phenotypic abnormalities was highest (37.8 per cent) in the autosomal mosaics and lowest (10.5 per cent) in the sex chromosome mosaics. The average rate for cytogenetic confirmation was 70 per cent.     

Normal development in two six-year-old boys born after prenatal diagnosis of trisomy 20 mosaicism

Prenatal diagnosis of trisomy 20 mosaicism was made in two pregnancies by chromosome analysis of cultured amniotic fluid cells. In both cases, the pregnancy continued to term and a healthy male infant was delivered. Regular assessments up to the age of 6-5 years revealed normal physical and intellectual development in both children.     

Unexpected structural chromosome rearrangements in prenatal diagnosis

Among 5315 prenatal diagnoses performed for various indications (maternal age, neural tube defect, metabolic diseases, X-linked diseases, pathologic pregnancies) 29 unexpected structural chromosome rearrangements were found in fetal cells. Fourteen were de novo chromosome rearrangements, six unbalanced, and eight balanced. Fifteen were inherited and balanced rearrangements. This high frequency of structural anomalies is discussed.     

Mitomycin C induced chromosome damage in fetal blood cultures and prenatal diagnosis of fanconi's anaemia

We report the use of fetal blood for the prenatal diagnosis of Fanconi anaemia (FA). The clastogenic action of Mitomycin C (MMC) is compared in blood cultures from different fetuses, normal controls and FA heterozygotes. The fetus at risk is shown to suffer from FA on the grounds of excessive chromosome breakage, both spontaneous and MMC induced.     

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.     

Partial trisomy 20p resulting from recombination of a maternal pericentric inversion: case report of a prenatal diagnosis by chorionic villus sampling

We report a case of prenatal diagnosis of trisomy 20p resulting from a maternal pericentric inversion. The diagnosis was confirmed on both chorionic villi and amniotic cells. This case underlines the fact that prenatal ultrasound diagnosis of this structural anomaly is difficult. The only early sonographic feature was increased nuchal translucency. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of trisomy 20 by chorionic villus sampling (CVS): a case report with long-term outcome

A case of prenatally diagnosed non-mosaic trisomy 20 in cells cultured from a chorionic villus sample (CVS)is presented. The term placental karyotype was also non-mosaic trisomy 20. The karyotype of thenewborn was 46,XY/47,XY,+20 in foreskin cultures and in a second skin culture; blood lymphocyte culture was 46,XY. Aside from diffuse, hypopigmentary swirls along the lines of Blaschko observed on hisextremities and trunk, referred to as hypomelanosis of Ito, the patient is clinically normal at 8¾ years ofage. In addition, he is one of the oldest reported cases of mosaic trisomy 20 confirmed after birth forwhich the clinical outcome has been monitored. This case demonstrates that these trisomy 20 findings are compatible with normal psychomotor development and phenotype. Copyright © 2001 John Wiley & Sons, Ltd.