Case Of Mosaic Trisomy Research Articles

Prenatal diagnosis of mosaic trisomy 2 and literature review

BackgroundWe presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and non-invasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality.ResultsCytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY,+2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases’ cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure.ConclusionsWe presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.

Prenatal diagnosis of mosaic trisomy 2: a case report

We reported a case of mosaic trisomy 2. The patient was a 29-year-old gravida who underwent amniocentesis at 20 weeks of gestation because of high risk of trisomy-21 in the first trimester screening. The test result revealed a karyotype of 47, XN, +2[10]/46, XX[40]. At 26 gestational weeks, the fetus was found severe fetal growth restriction and oligohydramnios which was considered to be at risk of mosaic trisomy 2. The pregnancy was terminated at 27+ gestational weeks. The fetus had obviously abnormal appearances, including dolichocephaly, low-set ears, and micromandible. Autopsy was not performed due to the parents' refusal. Key words: Trisomy; Chromosomes, human, pair 2; Chimera; Prenatal diagnosis; Amniocentesis; Abnormalities, multiple

Development of patients with 47,XX,+13/45,X mosaics: Case report and review of the literature

Very few cases of mosaic trisomy 13 combined with a monosomy X have been reported. It can be assumed that most likely the zygote was 47,XX,+13 and 2 chromosomes (13 and X) were lost simultaneously during an early postzygotic division. Here, we reported a 3-year-old girl with mosaicism of trisomy 13 and monosomy X. The child had a short neck, hypertelorism, depressed nasal ridge, epicanthal fold, mid-facial hypoplasia, thin upper lip, long philtrum, ear anomalies, postaxial polydactyly, atrial septal defect, hydronephrosis, and sensorineural hearing loss. Her weight and length were consistently below the fifth centile. She demonstrated global developmental delay when evaluated at 10 and 16 months. The range of developmental quotients (DQs) was from 0.6 to 1.1; the personal-social part was the best, and gross motor development was the worst. When evaluated at 31 months, the DQs of motor development were from 0.52 to 0.69, the object manipulation subscale was 0.52, the visual-motor integration subscale was 0.59 and the mental DQ was 0.52. Her social-behavior part was the best, language was the worst and the DQs had dropped with growth. This is a case report of global development in a girl with mosaicism of trisomy 13 and monosomy X. The majority of physical anomalies observed tend to be mild and non-life threatening. Her DQs dropped with growth, and the language and mental development were significantly delayed after 30 months.

Mosaic Trisomy 9 Presenting with Congenital Heart Disease, Facial Dysmorphism and Pigmentary Skin Lesions: Intricate Issues of Genetic Counseling

Chromosomal mosaicism for full aneuploidy involving chromosome 9 is an uncommon chromosomal abnormality. Mosaic trisomy 9 clinical manifestations are highly variable and difficult to predict. The authors present a case of mosaic trisomy 9 with typical clinical manifestations(facial dysmorphism, various internal organ malformations and severe psychomotor retardation), pigmentary mosaic skin lesions along the lines of Blaschko and evidence of maternal uniparental disomy in skin.

Oral Characteristics of Trisomy 8 and Monosomy 18: A Case Report

Several reports described various mosaic chromosomal syndromes characterized by alterations originated by either an excess or deficit in the number of chromosomes. A case of mosaic trisomy 8 and monosomy 18 with significant involvement of the oral cavity is described, both in terms of general medicine and from a dental-oral perspective, and the treatment plan was planned and discussed.Regular follow-up visits enabled to verify significant improvement in all parameters of the patient’s oral health, which urged us to press on with our quest to protect the right to health of patients affected by disabilities.

An incomplete trisomy 3 rescue resulting in a marker chromosome and UPD(3)—difficulties in interpretation

Trisomy 3 and marker chromosomes derived from chromosome 3 are rare cytogenetic findings. Confined placental mosaicism (CPM) of trisomy 3 was reported and in such cases, intrauterine growth retardation (IUGR) and intrauterine fetal death (IUFD) were occasionally seen. A case of trisomy 3 mosaicism in amniotic fluid was once detected in a newborn with a normal phenotype at birth and symmetric IUGR, probably resulting from the placental trisomic cell lines (Zaslav et al., 2004). There are only four cases of mosaic trisomy 3 in liveborn infants (confirmed in blood lymphocytes) with all showing an abnormal phenotype (Schinzel, 2001). There are several (19) published reports of chromosome-3-derived marker chromosomes (patients with complex karyotype, unpublished cases and tumor cell lines were excluded; http://www.med.uni-jena.de/fish/ sSMC/03.htm#unclear). Nine cases showed a normal phenotype; however, three of them were prenatal cases not evaluated after birth. An abnormal phenotype was reported in ten cases. We present the first documented case of an ‘incomplete’ trisomy 3 rescue, which resulted in an extra chromosome-3-derived marker chromosome in the fetus. Fluorescent in situ hybridization (FISH) and DNA studies were performed in order to characterize the marker chromosome and to elucidate the mechanism of formation, respectively. In order to assess a genotype–phenotype correlation, we compared our case with similar cases in the literature.

Prenatal diagnosis of trisomy 16 mosaicism manifested as pulmonary artery stenosis

Trisomy 16 mosaicism detected at midtrimester amniocentesis is rare and indicative of true fetal mosaicism. We report a case of mosaic trisomy 16 diagnosed by amniocentesis in which the sonographic findings included fetal pulmonary artery stenosis, a single umbilical artery, and early onset fetal growth restriction. The pregnancy was legally terminated. A review of previous reports suggests that abnormalities of outlet tracts are rarely encountered in fetuses with trisomy 16 mosaicism revealed via amniocentesis.

Mosaicismo de trisomía 9: caso de larga supervivencia

Trisomy 9 is an uncommon chromosome abnormality that may be seen in a mosaic or non-mosaic state. To better define the phenotype and prognosis of this disorder we report a new case of mosaic trisomy 9 with a long-term survival. We present the case of a female patient, born from the first pregnancy of a healthy couple. Fetal ultrasounds disclosed intrauterine growth retardation and oligohydramnios. Cesarean section was performed in the 34th week. Birth weight was 1,478 g. Neonatal examination showed: dolichocephaly; hypotelorism, microphthalmia, short palpebral fissures; broad-based nose with bulbous tip; micrognathia; low-set malformed ears; abnormal hands and feet; no other malformations. The initial karyotype determination was normal (46,XX). At 17 months of age, a second karyotype was requested because the patient developed severe psychomotor retardation. Chromosome analysis showed mosaic trisomy 9 (46,XX/47,XX, + 9). Six months later, a single upper central incisor was noted. To our knowledge, this feature has not been reported previously in the trisomy 9. The patient is now 4 years old. She shows severe psychomotor retardation, but no other complications. It is important to be aware of the possibility that mosaicism may exist in a patient with normal blood karyotype and abnormal phenotype. We conclude that a great number of cells is needed in order to obtain a correct karyotype diagnosis. Correct diagnosis is essential to define the prognosis and provide accurate genetic counselling.

Are Duane syndrome and infantile esotropia allelic?

Purpose:To evaluate the clinical overlap of families with Duane syndrome and infantile esotropia to determine whether the identification of genes for Duane syndrome may explain some cases of infantile esotropia. Methods:Three separate groups of patients were evaluated. 1) Families with features of infantile esotropia were identified through the Strabismus Inheritance Study Tasmania (SIST). Clinical details of participants and their families were reviewed for any cases of Duane syndrome. 2) Cases of Duane syndrome were identified through the clinical diagnostic database at the Royal Children's Hospital, Melbourne, and private ophthalmology clinics in Melbourne and Tasmania. Previous medical notes were reviewed and family history of strabismus noted. All affected individuals were invited for re-examination in cases where a positive family history of strabismus was reported; siblings, parents, and other family members, where appropriate, were invited to be examined for signs of Duane syndrome or infantile esotropia. 3) Cases of mosaic trisomy 8, which has been associated with Duane syndrome and infantile esotropia, were reviewed for signs of strabismus. Results:A total of 133 families from the SIST were reviewed, but no ‘pure’ families of Duane syndrome were identified. Two families with infantile esotropia had several members affected with Duane syndrome. Of the 40 index cases with Duane syndrome whose families agreed to be involved in the study, 21 had a family history of ocular motility disorders, but only two of these families had multiple cases of Duane syndrome. From 24 cases with mosaic trisomy 8, one individual case had Duane syndrome and another had mild congenital cataracts and infantile esotropia. Conclusions:There is clinical overlap in families with Duane syndrome and infantile esotropia. We confirmed the previous association of mosaic trisomy 8 with both Duane syndrome and infantile esotropia. These data suggest that the two conditions may be allelic and may be due to a gene on chromosome 8.

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.

High resolution comparative genomic hybridisation in clinical cytogenetics

High resolution comparative genomic hybridisation (HR-CGH) is a diagnostic tool in our clinical cytogenetics laboratory. The present survey reports the results of 253 clinical cases in which 47 abnormalities were...

Variable levels of mosaicism for trisomy 21 in a non-immune hydropic infant with chylothorax

We report the first case of mosaic trisomy 21 with non-immune hydrops fetalis and bilateral chylothoraces. Prenatal fetal blood karyotype analysis of 15 fetal cells revealed a 46,XX karyotype. Aggressive prenatal management, including fetal thoracocentesis and pleuro-amniotic shunt, was performed. A clinical phenotype of Down syndrome was apparent after the gross oedema had subsided. Subsequent chromosome study of neonatal blood lymphocytes showed mosaic trisomy 21 with 23 per cent trisomic cells. Review of the initial fetal blood sample identified trisomy in 5 per cent of 134 cells. Follow-up study at five months showed no trisomy 21 in 100 cells. This case illustrates the variable levels of mosaicism manifest in the peripheral blood of an infant with obvious Down syndrome phenotype, and the limitation of cytogenetic analysis of peripheral lymphocytes alone in prenatal and postnatal detection of low levels of mosaicism.

Atypical manifestations of two cases of trisomy 9 syndrome: Rethinking development delay

Trisomy 9 syndrome is characterized by "bulbous" nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous systems. With the exception of one reported case study, all surviving infants have had severe mental impairment. The prospect of severe mental retardation often overwhelms parents who are faced with prenatal diagnosis of trisomy 9. We report on two new cases of mosaic trisomy 9, both of whom are only mildly developmentally delayed. One patient presented with the distinctive facial appearance, large fontanels, and joint abnormalities. The other had none of the typical congenital abnormalities. However, the patient was found to have a congenital heart defect and hypoplastic left heart syndrome, which to our knowledge has not been reported previously in the trisomy 9 syndrome. When these two patients are added to the published patients with this syndrome, there appears to be a range of manifestations, especially with respect to mental status, which has not fully been recognized.

Atypical manifestations of two cases of trisomy 9 syndrome: Rethinking development delay

Trisomy 9 syndrome is characterized by “bulbous” nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous systems. With the exception of one reported case study, all surviving infants have had severe mental impairment. The prospect of severe mental retardation often overwhelms parents who are faced with prenatal diagnosis of trisomy 9. We report on two new cases of mosaic trisomy 9, both of whom are only mildly developmentally delayed. One patient presented with the distinctive facial appearance, large fontanels, and joint abnormalities. The other had none of the typical congenital abnormalities. However, the patient was found to have a congenital heart defect and hypoplastic left heart syndrome, which to our knowledge has not been reported previously in the trisomy 9 syndrome. When these two patients are added to the published patients with this syndrome, there appears to be a range of manifestations, especially with respect to mental status, which has not fully been recognized. Am. J. Med. Gen. 80:42–45, 1998. © 1998 Wiley-Liss, Inc.

Second and third trimester placental sampling: the benefits outweigh the pitfalls

SummaryPlacental biopsy was carried out in a total of 283 pregnant women between 1989 and 1994, the main indication being abnormal ultrasound signs (68.6 per cent) detected in the second and third trimesters. Successful sampling was achieved in 98.6 per cent of the cases. Excluding the first year, karyotypic results were obtained in 98.2 per cent of received samples. Out of these, 6.5 per cent were abnormal, and confirmed by the culture method, amniocentesis, or cordocentesis. In addition, one case of mosaic trisomy 8 was confirmed to be confined to the placenta (0.4 per cent). A spontaneous abortion rate of 2.1 per cent was observed, but not necessarily procedure-related. We had one false-negative report. In conclusion, we found placental sampling to be a useful method allowing a rapid decision to be taken regarding further management of at risk pregnancies.

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 15 1/2 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.