Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism

Abstract

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or after culture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.

Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration

“…If NIPT involves another trisomy than trisomy 13, 18, or 21, CPM is by far the most likely origin of the positive result in such cases. Although one could consider CPM to be irrelevant, it is associated with an increased risk of intrauterine growth retardation [38], fetal loss [39] or poor perinatal outcome [40]. Therefore, close follow-up investigations with ultrasound to monitor fetal growth in cases of CPM are indicated.…”

Fetal genital anomalies: an aid to diagnosis

“…In our series 9 of 24 cases (37.5%) had a syndromic diagnosis and 12 (50%) were in association with urinary tract anomalies, thus prenatal management should involve a multidisplinary approach. In a genotypically male fetus isolated hypospadia is not commonly seen prenatally, but it may be detected in fetuses conceived after intracytoplasmic sperm injection (ICSI) (Wennerholm et al, 2000) or where there is IUGR (Calzolari et al, 1986) as in three of our cases (1-3), particularly when uniparental disomy (UPD) (Hansen et al, 1997) or confined placental mosaicism (CPM) (Kalousek et al, 1991) can be aetiological factors. The aetiology in a genetic female fetus Bowing of the femur and tibia, talipes, hypoplastic scapulae, 11 pairs of ribs, micrognathia, small chest, cardiac anomalies is certainly narrower than in a genetic male, being predominantly confined to situations where underlying the pathology results in increased secretion of androgenic substances which result in virilization of the female genitalia, most commonly congenital adrenal hyperplasia or, rarely, a maternal tumor, for example a luteoma of pregnancy (Mazza et al, 2002).…”

Uniparental Disomy and Genome Imprinting: an Overview

“…They cover roughly one half of the 47 theoretical UPD possibilities for entire chromosomes (44 autosomes -22 for each sex -and 3 for the sex chromosomes -the paternal and maternal X and the XY pair). Described only once so far for some members, UPD has been repeatedly observed for others, such as mat (15) [5] and mat (16) [6]. Figure 1 illustrates these cases and shows the parental derivation of the chromosome, the genome imprinting effect and the occurrence of mosaicism.…”

“…the unmasking of recessive genes through isodisomy [4,6,10] 2. homozygosity acquired from a singly heterozygous parent [4,10], and 3. unusual and/or excessive syntenic homozygosity [21].…”

“…gamete complementation [6,7]; 2. mitotic reversal of a meiotic error: a) trisomy correction (reversal to disomy by extrachromosomal loss) [8, 91; b) monosomy erasure (by chromosome duplication or isochromosome formation) [5,[10][11][12][13][14][15], and c) chromosome substitution ("compensatory" with replacement of the marker by the normal partner) [16][17][18][19];…”