Trisomy 16 Mosaicism in Amniotic Fluid Cell Cultures

Abstract

Trisomy 16 mosaicism was found in amniotic fluid cells in a patient undergoing amniocentesis because of elevated second‐trimester maternal serum alpha‐fetoprotein (MSAFP) (2·80 MOM), a markedly elevated human chorionic gonadotropin level (hCG) (12·02 MOM), and a Down syndrome risk of 1:55. Ultrasound evaluation of the fetus indicated the presence of an atrial septal defect and clinodactyly. Cytogenetic analyses of various fetal tissues using fluorescence in situ hybridization (FISH) failed to detect substantial numbers of trisomy 16 cells; however, trisomy 16 mosaicism was identified in placental tissue. Molecular genetic analysis at five different loci [four analysed by polymerase chain reaction (PCR) and one by Southern blot analysis] failed to show any evidence for uniparental disomy. Although trisomy 16 cells could not be clearly demonstrated in the fetus, the presence of a clinically significant proportion of aneuploid cells early in development could not be excluded and it therefore cannot be assumed that a ‘confined placental mosaicism’ existed. The markedly elevated hCG and elevated MSAFP levels are consistent with abnormal placental function in trisomy 16 mosaicism. Serial ultrasound evaluation (to detect any late‐onset growth retardation) and fetal echocardiography may be indicated for patients with extraordinarily high levels of hCG, especially if MSAFP is also elevated.

Prospective prenatal investigations on potential uniparental disomy in cases of confined placental trisomy

“…The maternal hypertension and deteriorating renal function in the present UPD 16 case further support this hypothesis. Moreover, there appears to be an association between CPM for chromosome 16 and an unexplained abnormal profile of maternal serum markers (Vaughan et al, 1994;Zimmerman et al, 1995;Tantravahi et al, 1996), also pointing in the direction of a dysfunctional placenta. However, this cannot explain the presence of fetal congenital malformations in some cases of UPD 16.…”

Severe Fetal Malformations Associated with Trisomy 16 confined to the Placenta

“…Here we have described a second example of trisomy 16 CPM in a pregnancy with a malformed fetus, also in the absence of evidence for either trisomic cells or UPD in fetal tissues. The clinical features in these two cases appear dissimilar; however, postmortem information is not available in Tantravahi et al (1996), so further anomalies cannot be excluded.…”

“…In addition, polysplenia was also apparent. Tantravahi et al (1996) have described a fetus with an atrial septal defect and clinodactyly in association with trisomy 16 in amniotic fluid cells and in the placenta, but not detectable in the fetus itself; UPD in the fetus was also excluded. Here we have described a second example of trisomy 16 CPM in a pregnancy with a malformed fetus, also in the absence of evidence for either trisomic cells or UPD in fetal tissues.…”

“…We are aware of only one other report of similar cytogenetic and molecular genetic findings associated with abnormality other than IUGR in the fetus (Tantravahi et al, 1996).…”

Partial trisomy 10 (10q11.2→pter) and partial trisomy 18 (18p11.2→pter) associated with abnormal sonographic findings and a maternal serum screen‐positive result

“…The present case adds to the list of brain anomalies associated with trisomy 10p and demonstrates that fetuses with partial trisomy 10 (10q11.2→pter) and partial trisomy 18 (18p11.2→pter) may be associated with abnormal cerebellar development. In addition to Down syndrome, elevated maternal serum hCG in the second trimester has been reported to be associated with other chromosomal abnormalities, such as distal 5p deletion (cri-du-chat) syndrome 18,19 , a deletion of 18q22.2-qter 20 , an interstitial deletion of 4q12-q21.1 21 , a microdeletion of 17p11.2 22 , mosaic trisomy 20 23,24 , mosaic trisomy 16 25,26 , confined placental mosaicism (CPM) for trisomy 16 27 -29 , CPM for trisomies 9, 13, and 15 29 , CPM for trisomy 2 30 , CPM for trisomy 14 and maternal uniparental disomy 31 , sex chromosome abnormalities 32 , Turner syndrome 33 and marker chromosomes 21 . Several reports have shown an association between elevated hCG levels and pregnancy complications such as IUGR 34 , hypertension 35 , fetal malformations 36,37 , adverse perinatal outcome 18,38 and molar pregnancies 39 .…”