Prenatally detected trisomy 4 and 6 mosaicism—cytogenetic results and clinical phenotype

We report on a live-born male with 46,XY/47,XY+4/47,XY,+6 mosaicism. Trisomy 4 mosaicism was detected by karyotyping chorionic villus samples (CVS) and was confirmed by the analysis of 16 metaphases obtained from cultured amniotic fluid cells. Eight metaphases were normal (46,XY), two had trisomy 4 (47,XY,+4), and two had trisomy 6 (47,XY,+6). Two postnatal chromosomal analyses of blood lymphocytes at birth and at the age of one week were normal. Chromosomal analysis of cultured skin fibroblasts from the right inguinal region at the age of 12 months revealed trisomy 4 (47,XY,+4) in 49 metaphases, trisomy 6 (47,XY,+6) in 2 metaphases, and a normal karyotype (46,XY) in 49 cells of the 100 analyzed metaphases, respectively. The main clinical findings consist of prenatal growth retardation, hypoplasia of the right side of the face, a dysplastic and posteriorly rotated right ear, a high vaulted palate, retrognathia, aplasia of the right thumb, hypoplasia of the fingernails, a deep sacral dimple, and patchy skin hypopigmentation of the right leg. When last seen at the age of 14 months, his development was nearly normal. Five patients with trisomy 4 mosaicism have been reported previously, but none with an additional trisomy 6 mosaicism. Copyright © 2003 John Wiley & Sons, Ltd.     

Management of prenatally detected trisomy 8 mosaicism

We report on ten pregnancies with trisomy 8 mosaicism. Nine cases were prenatally detected in chorionic villi (n=6), amniotic fluid (AF) cells (n=2) or fetal blood (FB) lymphocytes (n=1). Follow-up laboratory investigations showed confined placental mosaicism (CPM) or pseudomosaicism in eight cases. In one case with ultrasound abnormalities, trisomy 8 mosaicism was detected in FB cells although cultured AF cells showed normal cells only. Another case of mosaic trisomy 8 was prenatally missed; cytogenetic analysis of short-term cultured villi revealed a normal male karyotype, while postnatally, trisomy 8 mosaicism was detected in peripheral blood lymphocytes and skin fibroblasts of the affected child. These findings indicate the difficulties in the prenatal diagnosis of trisomy 8 mosaicism. When found in chorionic villi, it mostly represented CPM, while in a case of true fetal trisomy 8 mosaicism, the cytotrophoblast cells showed a normal karyotype. So, the cytotrophoblast compartment of chorionic villi is a poor indicator of the presence or absence of fetal trisomy 8 mosaicism. Follow-up investigations including amniocentesis and especially fetal blood sampling are required to come to a definite prenatal diagnosis of trisomy 8 mosaicism. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of trisomy 6 mosaicism

We report on a fetus with multiple congenital anomalies detected at the prenatal ultrasound examination and a trisomy 6 mosaicism in the amniocytes. The pregnancy was interrupted in the 18th gestational week and the autopsy revealed malformations including cleft right hand, arthrogryposis and hypoplasia of the 4th digit of the left hand, syndactylies and overlapping toes, facial dysmorphism with hypertelorism and low-set ears, ventricular septum defect (VSD), intestinal malrotation and scoliosis. Trisomy 6 mosaicism was detected in cultured amniocytes (13.3%), confirmed in umbilical cord fibroblasts (40%) and by fluorescence in situ hybridization on other fetal tissues. Trisomy 6 mosaicism is a very rare finding with only eight cases previously reported to our best knowledge. Copyright © 2005 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.     

Prenatally detected double trisomy: Klinefelter and Down syndrome

Double trisomies are a rare occurrence. We report the first case of a Down and Klinefelter's syndrome (48,XXY,+21) in a fetus that was prenatally diagnosed during the 15th week of pregnancy. Even though the nasal bone was present, and the color-Doppler study of the ductus venosus and the nuchal thickness were normal, the maternal serum test results indicated an increased risk of Down syndrome and consequentially a genetic amniocentesis was performed. A 48,XXY,+21 karyotype was observed and the patient decided to terminate the pregnancy. In this case, we did not find the typical ultrasound (US) signs that would have led us to the chromosomopathy; furthermore, we emphasize the advantages of using biochemical screening which, in our case, were crucial in arriving at the correct diagnosis. Copyright © 2006 John Wiley & Sons, Ltd.     

Parental mosaic trisomy 21 detected following maternal cell contamination of an amniotic fluid specimen from a normal male pregnancy

We report a case of maternal mosaic trisomy 21 ascertained at prenatal diagnosis as a result of maternal cell contamination of an amniotic fluid sample. A 34 year old female was referred for karyotyping because of a previous trisomy 21 pregnancy. Chromosome analysis of primary in situ cultures showed a karyotype of 47,XX, + 21[6]/46,XY[32]/46,XX[2]. Molecular testing demonstrated maternal cell contamination of the amniotic fluid sample and G-banded karyotyping of maternal blood showed that 3/200 cells had trisomy 21, consistent with the mother being a Down syndrome mosaic. A normal male baby with a 46,XY chromosome complement was delivered at 30 weeks. This case emphasises the need for close collaboration between cytogenetic and molecular genetics laboratories in resolving unusual cases of mosaicism. Copyright © 2007 John Wiley & Sons, Ltd.     

Structural chromosomal mosaicism and prenatal diagnosis

True structural chromosomal mosaicism are rare events in prenatal cytogenetics practice and may lead to diagnostic and prognostic problems. Here is described the case of a fetus carrying an abnormal chromosome 15 made of a whole chromosome 2p translocated on its short arm in 10% of the cells, in association with a normal cell line. The fetal karyotype was 46,XX,add(15)(p10).ish t(2;15)(p10;q10)(WCP2+)[3]/46,XX[27]. Pregnancy was terminated and fetus examination revealed a growth retardation associated with a dysmorphism including dolichocephaly, hypertelorism, high forehead, low-set ears with prominent anthelix and a small nose, which were characteristic of partial trisomy 2p. Possible aetiologies for prenatal mosaicism involving a chromosomal structural abnormality are discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Sex chromosome mosaicism not detected at amniocentesis

Amniocentesis was performed because of a fetal abdominal wall defect, and a 45,X karyotype was obtained. A near-normal male infant with no features of Turner syndrome was delivered. The karyotype of the infant was 45,X/46,X, dic(Y)(q11), with each of the cell lines present in approximately 50 per cent of the lymphocytes and fibroblasts examined.     

Outcome of prenatally diagnosed trisomy 6 mosaicism

We report the prenatal diagnosis of trisomy 6 mosaicism via amniocentesis, in which trisomy 6 cells were identified in three of five culture vessels with 33% (5/15) of colonies showing trisomic cells. The pregnancy was electively terminated and examination revealed minor abnormalities (shortening of the femurs, micrognathia, posterior malrotation of the ears, and bilateral camptomelia of the second digit of the hands and fifth digits of the feet). Cytogenetic analysis of the placenta showed trisomy 6 in 100% of 20 cells studied. Karyotype was 46,XX in 100 cells examined from fetal skin. There are relatively few prenatally diagnosed cases of mosaic trisomy 6 at amniocentesis. Confined placental mosaicism (CPM) has been postulated in other cases where follow-up cytogenetic studies were not available. The present case differs from those previously reported, as it appears to represent CPM of chromosome 6 with phenotypic effects to the fetus. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of complete sole trisomy 1q

The prenatal diagnosis of a complete trisomy of the long arm of chromosome 1 is reported. Major ultrasound findings included: nuchal thickening, bi-temporal narrowing, a single choroid plexus cyst, andmild ventriculomegaly. There was a mass in the chest and abdomen, pleural effusion, ascites and a hyperechoic bowel. Skin edema was present. The fetus died at 26 weeks' gestation. A literature review is presented of 17 de novo and two inherited cases with only trisomy 1q. Of note is the fact that 3/5 prenatally detected 1q trisomies have teratomas. A review of the literature reveals a dismal outcome fortrisomy 1q cases if the duplication involves bands 1q25→q32. Copyright © 2001 John Wiley & Sons, Ltd.     

Trisomy 13 mosaicism: study of serial cytogenetic changes in a case from early pregnancy to infancy

We report a patient whose chorionic villus sampling showed a nonmosaic trisomy 13 [46,XX,der(13;13)(q10;q10)]. Subsequent amniocentesis and cordocentesis showed varying percentages of abnormal cells (77 and 78% in two amniocentesis; 14% in cordocentesis) and mosaic trisomy 13 was impressed. Prenatal fetal ultrasound scanning revealed only mild structural abnormalities (echogenic cardiac foci, transient lemon head, transient skin oedema). The mother chose to continue the pregnancy. Karyotyping of the cord blood, peripheral blood, umbilical cord, urine, and chorion were performed postpartum. The process of correction appeared to exist in the placenta (indirect evidence from coexistence of trisomy 13 [46,XX,der(13;13)(q10,q10)], euploidy [46,XX], aneuploidy [46,XX,–13, +mar], and monosomy 13 [45,XX,–13] in the chorion at birth). The baby had survived beyond eight months of age at the time of submission. Few structural abnormalities except low-set ears, absence of the 12th rib, and cardiomegaly with ventricular septal defect, were noted postnatally. The growth reached 95th percentile at the age of one month. Development milestones were not delayed at serial evaluations. Her ventricular septal defect was corrected surgically at the age of six months. Karyotypes of her skin fibroblasts, blood lymphocytes, and cardiac tissue were all normal [46,XX] at the time of surgery. Difficulties of the genetic counseling are also discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

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 15¹/₂ 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.     

Pre- and perinatal findings in partial trisomy 7q resulting from balanced parental translocations t(7;21) and t(4;7)

We report on a fetus and a newborn, both with partial trisomy 7q21→qter due to different familial translocations, t(7;21)(q21.2;p12) and t(4;7)(q35;q21.2). Postmortem examination of the 19-week-old female fetus disclosed dysmorphic features, cleft palate, anomalies of the great vessels, intestinal malrotation and uterus bicornis. The newborn girl revealed a pattern of minor anomalies, cleft palate, cerebellar hypoplasia, and anomalies of pancreas, gall bladder and appendix. The clinical findings in three other reported fetuses with partial trisomy 7q described so far are reviewed. A duplication 7q21→qter, as found in the propositi, has only been described in 11 patients who all had a concurrent partial monosomy. Patient 1 is particularly interesting since she is, to our knowledge, the first reported case with pure trisomy 7q21/22→qter. We reviewed the phenotype of the previously described patients, compared it with the propositae, and summarized the clinical features of pure trisomy 7q21/22→qter. Copyright © 2001 John Wiley & Sons, Ltd.     

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 diagnosis of mosaicism for triploidy and trisomy 13

Mosaicism for trisomy 13 and triploidy was detected by amniocentesis performed at 18 weeks' gestation because of fetal anomalies. Pregnancy continued and a live-born male was delivered vaginally at 37 weeks. The infant had features common to both trisomy 13 and triploidy: intrauterine growth retardation (IUGR), small abnormal ears, cleft palate, and a small jaw. In addition, he had complete cutaneous syndactyly of fingers 3 and 4 and partial syndactyly of the toes, as seen in triploidy. Mixoploidy for trisomy 13 and triploidy was confirmed postnatally in blood, skin, and placenta. Examination of chromosome heteromorphisms and DNA markers suggested the presence of two maternal contributions in the triploid cell line. In addition, the extra chromosome 13 in the trisomic cell line was derived from the mother. Copyright © 2001 John Wiley & Sons, Ltd.