Postnatal confirmation of prenatally diagnosed trisomy 16 mosaicism in two phenotypically abnormal liveborns

Abstract

Two phenotypically abnormal liveborns in whom trisomy 16 mosaicism was diagnosed prenatally by amniocentesis are described. Analysis of a percutaneous umbilical blood sample in one case revealed a normal chromosomal complement. Ultrasound examinations performed at the time of amniocentesis were normal. Serial sonography during the late second and third trimesters demonstrated progressive intrauterine growth retardation (IUGR) in both fetuses and a cardiac defect in one. At birth, both infants had dysmorphic features and multiple congenital anomalies. Trisomy 16 mosaicism was confirmed postnatally in both infants in skin fibroblasts; however, peripheral blood samples contained only chromosomally normal cells. The two mosaic trisomy 16 cases described in this report, together with the five confirmed cases reported previously, demonstrate the need for caution in the counselling of patients when trisomy 16 mosaicism is diagnosed prenatally in amniotic fluid samples. Such cases potentially can result in the birth of dysmorphic infants with significant birth defects, growth retardation, and possible developmental disabilities.

Trisomy 16 Mosaicism in Amniotic Fluid Cell Cultures

“…This case was initially identified as a result of elevated MSAFP and highly elevated hCG. A number of cases have been noted to have somewhat elevated MSAFP (Hajianpour et al, 1992;Devi et al, 1993;Rosenblum-Vos et al, 1993;Pletcher et al, 1994;Vaughan et al, 1994;Meck et al, 1995;Davies et al, 1995;Zimmermann et al, 1995) but the more striking finding in our case is the hCG value. At the University of Connecticut laboratory, in a total of 32 676 triple marker screening tests, only four had hCG exceeding 10 MOM.…”

“…The first well-characterized case of a newborn with trisomy 16 mosaicism was described by Gilbertson in 1990 and since then, there have been at least ten other cases in which trisomy 16 mosaicism has been established on the basis of both normal and trisomy 16 cells present in newborn or fetal tissues (Table I). The main features associated with the disorder have been reviewed by Pletcher et al (1994) and include intrauterine growth retardation (IUGR), cardiac defects, and craniofacial and body asymmetry. In addition to those cases where trisomy 16 mosaicism has been confirmed in fetal tissue, there have been numerous instances where trisomy 16 has been noted during prenatal diagnostic testing and where there have been adverse pregnancy outcomes, but where confirmatory cytogenetic analyses have failed to identify trisomy 16 cells in fetal or newborn tissues (reviewed by Wolstenholme, 1995).…”

Evidence for imprinting on chromosome 16: The effect of uniparental disomy on the outcome of mosaic trisomy 16 pregnancies

“…Although cases with poorer outcome (e.g., severe growth restriction or presence of malformation) may have been more likely to be submitted for UPD testing, there should be no bias regarding the presence or absence of UPD among these cases. Data from thirty-three cases were from other published reports to date [Bennett et al, 1992;Hajianpour et al, 1992;Jalal et al, 1992;Williams et al, 1992;Lindor et al, 1993;Sutcliffe et al, 1993;Garber et al, 1994;Pletcher et al, 1994;Vaughan et al, 1994;Davies et al, 1995;Hajianpour, 1995;Whiteford et al, 1995;Zimmerman et al, 1995;Brandenburg et al, 1996;O'Riordan et al, 1996;Tantravahi et al, 1996;Hsu et al, 1997;Moore et al, 1997;Sanchez et al, 1997;Smith et al, 1997;Wang et al, 1997;Astner et al, 1998;Benn, 1998;Hsu et al, 1998;Sirchia et al, 1998;Van Opstal et al, 1998;Wang et al, 1998;Abu-Amero et al, 1999;Farra et al, 2000;Johnson et al, 2000;Van Opstal et al, 2001]. Although a large series of trisomy 16 cases was reviewed in Benn [1998], these data were verified from the original sources and care was taken to eliminate duplicated cases (e.g., Vancouver study cases published by other centers and cases published in two separate reports).…”

Prenatal Diagnosis of an Infant With Mosaic Trisomy 16 of Paternal Origin

“…While complete trisomy 16 appears uniformly lethal, survival of infants with mosaic trisomy 16, although rare, has been documented (Greally et al, 1990;Gilbertson et al, 1990;Devi et al, 1993;Lindor et al, 1993;Garber et al, 1994;Pletcher et al, 1994;Hajianpour and Habiabian, 1995). To date, all molecular studies of parental origin of trisomy 16 have demonstrated that the extra chromosome is maternally derived.…”