Trisomy 20 mosaicism confirmed in a phenotypically normal liveborn

Prenatal diagnosis of trisomy 20 mosaicism in this case was based on cytogenetic analysis of cultured amniotic fluid cells (23/52 cells were trisomy 20 representing cells from each of four primary cultures). The pregnancy continued to term and the mosaicism was confirmed in the phenotypically normal male neonate by analysis of cultured foreskin fibroblasts (7/49 cells + 20) and placental cells 20/20 cells + 20) whereas the peripheral lymphocytes were cytogenetically normal (20/20 cells were 46,XY). This represents the first confirmation of trisomy 20 mosaicism in a phenotypically normal full-term neonate.     

Trisomy 20 mosaicism

A further case of trisomy 20 mosaicism found at amniocentesis is presented. Pregnancy was terminated, the fetus showed facial dysmorphia and minor cardial and renal anomalies. 19 published reports of true trisomy 20 mosaicism at amniocentesis are reviewed. Five pregnancies resulted in obviously normal newborns. The significance of mostly minor anomalies found at autopsy of 7 fetuses remains unclear. With regard to genetic counselling the significance of trisomy 20 mosaicism is summarized as follows: (1) true trisomy 20 mosaicism in amniotic fluid cells reflects mosaicism of the fetus; (2) severe malformation is not a major feature of trisomy 20 mosaicism; (3) the risk of mental retardation is still undetermined, due to limited experience. However, there is no definite proof that the condition is harmful at all.     

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.     

Trisomy 20 mosaicism in amniotic fluid cells

The significance of trisomy 20 mosaicism in cultured amniotic fluid cells is still confusing. We report a case of amniotic cell normal/trisomy 20 mosaicism diagnosed prenatally. The pregnancy was carried to term and a normal baby girl was delivered. The authors consider that in cases of amniotic fluid cell normal/trisomy 20 mosaicism the termination of pregnancy may not be advised, however, the parents should be fully informed.     

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.     

Trisomy 12 mosaicism in phenotypically normal fetuses following prenatal detection

We report three cases of amniocentesis in which mosaicism for trisomy 12 was detected in two or more independent cultures. The parents elected to terminate the pregnancy in all three cases. Follow-up studies in two of the cases confirmed the mosaicism in fetal tissues (in subcutaneous tissue in one case; in fetal lung in the other), but not in blood. No fetal anomalies were evident by ultrasound or at autopsy. These results along with other reported cases demonstrate the difficulty in counselling for mosaic trisomy 12.     

Trisomy 12 mosaicism detected by mid–trimester amniocentesis

Trisomy 12 mosaicism was found in about 15 per cent of cultured amniocytes obtained from a 32-year-old white female at 17·6 weeks of gestation. Termination of pregnancy was elected and multiple tissues were obtained for chromosome analysis. Of 158 cells examined, only 1 cell in placenta was found with an extra number 12 chromosome. Pathological examination of the fetus did not reveal significant physical abnormalities. This report illustrates the difficulty of confirming trisomy 12 mosaicism which has been detected on prenatal diagnosis. The presence of trisomy 12 in one placental cell obtained from the curettage specimen suggests the possibility of confined placental mosaicism in this case.     

Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.     

Prenatal detection of chromosomal mosaicism

A significant problem associated with cytogenetic prenatal diagnosis is distinguishing between true and pseudomosaicism. This becomes a diagnostic dilemma when fetal mosaicism corresponds with a known clinical entity. True mosaicism reportedly occurs with a frequency of 0·2 per cent and pseudomosaicism in 0·7 per cent to 2·7 per cent of cases. In the past 12 months, our laboratory has completed 522 fetal karyotypes. Nine cases were found to demonstrate mosaicism, 4 true mosaics (0·8 per cent) and 6 pseudomosaics (1·1 per cent). One case demonstrated both true and pseudomosaicism. In all cases of true mosaicism, the pregnancy was continued and karyotypes completed at birth. Our results demonstrate a danger of rigid adherence to the criteria for true and pseudomosaicism in the examination of amniotic fluids. It is suggested that the criteria established for true and pseudomosaicism may not be valid when an aberrant cell line is found in a single flask and when that aberrant cell line is compatible with a known clinical entity due to a chromosome anomaly.     

Trisomy 14 mosaicism leading to cytogenetic discrepancies in chorionic villi sampled at different times

Short- and long-term cultures of chorionic villi obtained in the 11th week of pregnancy revealed trisomy 14. After induced abortion trisomy 14 mosaicism was established in fetal skin and umbilical cord tissue while a second long-term culture of chorionic villi exhibited a normal karyotype. The results of the pathological investigations are discussed with respect to the cytogenetic findings.     

Trisomy 5 mosaicism detected prenatally with an affected liveborn

This paper reports a case of chromosomal mosaicism for trisomy 5 recovered from amniotic fluid cells and from skin fibroblasts of a liveborn dysmorphic male. Routine amniocentesis was performed at 16 weeks' gestation because of parental concern. Trisomy 5 cells were measured from 25 per cent of amniocytes from two culture vessels. No further invasive testing was performed until 32 weeks' gestation, at which time ultrasound examination showed fetus with intrauterine growth retardation. Fetal blood sampling was then performed, with only karyotypically normal cells recovered. At birth, the child was found to have multiple dysmorphic features and congenital anomalies, including an eventration of the diaphragm and ventricular septal defect, both of which required surgical correction. Chromosomal analysis of cord blood lymphocytes indicated 46,XY; however, 20 per cent of the cultured fibroblasts obtained from the chest skin at the incision site for diaphragmatic repair had a 47,XY,+5 karyotype. Trisomy 5 mosaicism may be another example of tissue-limited mosaicism. Fetal blood sampling can then be falsely reassuring. Furthermore, because some cell lines rarely appear in lymphocyte populations, cytogenetic analysis of multiple tissues warranted as part of the evaluation of individuals with developmental delay and dysmorphic features.     

An infant with trisomy 9 mosaicism presenting as a complete trisomy 9 by amniocentesis

We present a case in which amniocentesis performed at 33 weeks' gestation because of symmetrical intrauterine growth retardation and decreased amniotic fluid volume led to the prenatal diagnosis of a fetus with a karyotype of 47,XX,+9, t(1;20)(q42;p11.2) pat, i.e., with an extra chromosome 9 and a balanced translocation between chromosomes 1 and 20. At delivery, the baby showed clinical features of trisomy 9, yet chromosome analysis of the cord blood revealed no trisomy 9 cells, a finding confirmed by neonatal blood karyotyping. The balanced translocation was present in all cells. A skin biopsy confirmed trisomy 9 mosaicism with 10 per cent trisomy 9 cells. The baby died at 6 weeks and an autopsy was obtained. Chromosome analysis of different organs demonstrated different frequencies of the mosaicism of trisomy 9. The possible underlying mechanism for the discrepancy between the karyotype results by amniocentesis and those of other tissues is discussed.     

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.     

Prenatal diagnosis of mosaic trisomy 9

Mosaic trisomy 9 was detected in an amniotic fluid cell culture from a 40-year-old woman evaluated because of advanced maternal age. After counselling, parents elected to terminate the pregnancy. On autopsy the fetus was found to have hydrocephalus and a single kidney. The diagnosis of trisomy 9 mosaicism was confirmed in cultured skin fibroblasts. This is the third reported case of trisomy 9 mosaicism diagnosed prenatally.     

Prenatal diagnosis of mosaicism 46, XX/46, XX, −21, +t(21q21q)

Mosaicism for a structural chromosome abnormality in amniotic cell cultures indicative of true fetal mosaicism is a rare event. In addition to the laboratory findings the clinical interpretation for counselling in such cases is based on observation of the same abnormality in liveborns as well as previous experience with prenatal diagnosis of the same or similar abnormalities. We report here the prenatal diagnos is of 46,XX/46,XX,−21,+t(21q21q) which was confirmed in fetal skin cell and amnion cell cultures.     

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.     

An accessory marker derived from chromosome 20 and its co-existence with a mosaic trisomy 20 cell line

We report a 16-month-old boy with delayed psychomotor development, dysmorphic features, and failure to thrive. He had a mosaic karyotype detected prenatally: mos 46,XY/47,XY,+r(20)/47,XY,+20. After birth, the abnormal cell lines were confirmed in a number of tissues. The small ring chromosome was identified using fluorescence in situ hybridization as derived from chromosome 20. We compared our patient with previously reported cases of mosaic trisomy 20 detected prenatally and associated with an abnormal phenotype. In an attempt to characterize an r(20) syndrome, we also compared our case with two similar reports in the literature.     

Follow-up of pregnancies complicated by placental mosaicism diagnosed by chorionic villus sampling

Thirty-nine (2.3 per cent) of 1724 chromosome studies from diagnostic chorionic villus samplings (CVS) done between 1983 and 1990 showed either level III (true) mosaicism (1.2 per cent) or level II (pseudo-) mosaicism (1.1 per cent) for chromosomal aneuploidy. Follow-up information on these 39 pregnancies was collected from questionnaires to families, paediatricians, and obstetricians. For all cases in which the pregnancy was continued and further testing was accomplished, the mosaicism was felt to be confined to the placenta. As compared with a control group of pregnancies evaluated by CVS with normal karyotypes, there was no increased incidence of pregnancy loss, congenital malformations, or developmental delay in the infants. Although intrauterine growth retardation occurred in several of the level III mosaic cases, adequate catch-up growth has been demonstrated.     

Further examples of trisomy-20 mosaicism in amniotic cell cultures

Amniotic fluid cultures from two patients showed trisomy-20 mosaicism. No trisomy-20 cells were found in a normal full term infant and in multiple tissue biopsies and fetal blood from a fetus after a termination of pregnancy. No definitive advice is yet possible for parents where trisomy-20 amniotic cell mosaicism is detected. Fetoscopy and fetal blood sampling are of no value and termination of pregnancy is not indicated by empirical evidence. Preferential trophoblastic non-disjunction (Kalousek and Dill, 1983) is discussed as a possible partial explanation for the variable occurrence and distribution of this type of mosaicism.     

Prenatal diagnosis of trisomy 9 mosaicism: Two new cases

We present two prenatal cases of trisomy 9 mosaicism, both of which presented intrauterine growth retardation (IUGR) and other abnormal ultrasound findings. In case A, mosaicism was found in amniotic fluid cell cultures, of which 65 per cent were trisomic cells, on average. In case B, trisomic cells were present in amniotic fluid cell cultures (12 per cent) but none were found in fetal cord blood. After autopsy, cytogenetic findings were confirmed in different tissue cultures. It is concluded that echographic indicators are a very useful tool for a correct prenatal diagnostic interpretation of trisomy 9. Suspected trisomy 9 mosaicism always requires further investigation and fetal cord blood cytogenetic analysis may not be considered as providing an accurate diagnosis of fetal trisomy 9.