Prenatal diagnosis of a fetus with pure partial trisomy 1q32-44 due to a familial balanced rearrangement

We diagnosed a pure partial trisomy of the long arm of chromosome 1 in a fetus with multiple malformations detected prenatally. The father was a carrier of a balanced rearrangement involving 46,XY,inv(1)(qter→p36::q32→qter::p36→q32). The fetus had preaxial polydactyly, low-set ears, macrocephaly, a prominent forehead, a broad and flat nasal bridge, a small mouth, an arched palate, micrognathia and unilateral renal agenesis. The couple had previously an infant with the same phenotypic abnormalities. The aberration was initially detected on amniocentesis with GTG banding and was confirmed by fluorescence in situ hybridization (FISH). Our case and other published pure trisomy 1q32-44 cases showed similarities, which allowed the further delineation of the trisomy 1q syndrome. Copyright © 2002 John Wiley & Sons, Ltd.     

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.     

A second case of intrauterine growth retardation and primary hypospadias associated with a trisomy 22 placenta but with biparental inheritance of chromosome 22 in the fetus

We report a case of severe intrauterine growth retardation (IUGR) and hypospadias in association with trisomy 22 diagnosed following chorionic villus sampling (CVS). Subsequent analysis of amniotic fluid cultures showed a normal male karyotype, 46,XY. As a previous case had been reported with similar abnormalities, in association with maternal uniparental disomy (UPD) 22, molecular studies were also performed. Microsatellite marker studies showed biparental inheritance. Follow-up studies after delivery showed a normal cell line in lymphocytes with the trisomy appearing to be confined to the placenta. The present case concurs with other earlier reports that maternal UPD for chromosome 22 has no impact on the phenotype. The features seen in the fetus are most likely the result of placental dysfunction due to trisomy, tissue-specific mosaicism and/or the effects of local growth restriction. Copyright © 2002 John Wiley & Sons, Ltd.     

False-positive diagnosis of trisomy 21 using fluorescence in situ hybridisation (FISH) on uncultured amniotic fluid cells

An amniocentesis was performed on a 22-week pregnancy following the detection of foetal abnormalities on ultrasound. A rapid aneuploid screen using fluorescence in situ hybridisation on uncultured amniotic fluid cells revealed 3 signals for chromosome 21, consistent with trisomy 21. In situ metaphase cultures revealed a 46,XY normal male karyotype. These discordant results may be explained by a sub-standard batch of the commercially available probe or alternatively, a very specific variation within the sample interacting with the probe. Alternative strategies are proposed in order to safeguard against inappropriate clinical action as a consequence of discordant results. Copyright © 2003 John Wiley & Sons, Ltd.     

Prenatal overgrowth and mosaic trisomy 15q25-qter including the IGF1 receptor gene

Overgrowth is rarely associated with chromosomal imbalances. Here, we report on a male foetus presenting with overgrowth and additional material on the short arm of one of the chromosome 15 in 12% of lymphocytes and 50% of amniotic cells. Parents' karyotypes were normal, indicating a de novo origin for this unbalanced rearrangement. Complementary studies using cytogenetic and FISH studies showed that this additional material resulted in a 15q25-qter trisomy and confirmed the presence of three copies of the insulin-like growth factor 1 receptor (IGF1R) gene, included in the trisomic region. Autopsy performed after termination of pregnancy revealed isolated overgrowth and absence of visceral malformations. The possible mechanisms and origins for the formation of this mosaic pure trisomy are complex. The present observation emphasises the hypothesis that the overgrowth phenotype, frequently reported in patients with trisomy including the 15q26 region, might be causally related to a dosage effect of the IGF1R gene, as well as the importance of chromosome analysis in patients with overgrowth. It also confirms that the overgrowth is of prenatal onset in those observations. Copyright © 2004 John Wiley & Sons, Ltd.     

Risk of amniocentesis in women screened positive for Down syndrome with second trimester maternal serum markers

In routine obstetrical practice, prior to offering invasive prenatal diagnosis, it is crucial to weigh the risks attendant on amniocentesis against the individual's risk of aneuploidy. We took advantage of a policy of follow-up of patients undergoing Down syndrome maternal serum screening to compare the rates of fetal loss before 24 weeks and of early premature delivery at 24–28 weeks between women who underwent amniocentesis and women who did not. A total of 54 902 patients entered the study, of whom 4039 (7.35%) were lost to follow-up and 387 were excluded because of a severe fetal abnormality. Of the 50 476 remaining patients, 3472 had an amniocentesis whereas 47 004 had not and served as controls. In the amniocentesis group, the fetal loss rate before 24 weeks was 1.12% (95% CI=1.08–1.15) and the 24–28 weeks premature delivery rate was 0.40% (95% CI=0.39–0.41) which was significantly higher than in controls (0.42% with 95% CI 0.41–0.43 and 0.24% with 95% CI 0.23–0.25, respectively). The 0.86% difference in adverse outcome rates between the amniocentesis and control groups may be attributable to amniocentesis and compares favourably with the positive predictive value of maternal serum markers (1.70%) observed in the present study. Copyright © 2002 John Wiley & Sons, Ltd.