Mosaic trisomy 16 ascertained through amniocentesis: Evaluation of 11 new cases

Trisomy 16, once thought to result uniformly in early pregnancy loss, has b een detected in chorionic villus samples (CVS) from on-going pregnancies an d was initially ascribed to a second, nonviable pregnancy. Prenatally detec ted trisomy 16 in CVS and its resolution to disomy has led to the reexamina tion of the viability of trisomy 16. This study evaluates 11 cases of mosai c trisomy 16 detected through second trimester amniocentesis. In 9 of the 1 1 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses wer e performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The li veborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them die d neonatally because of complications of severe congenital heart defects. T he three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pre gnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in si tu hybridization studies identified true mosaicism in 5 of 10 cases examine d, although the abnormal cell line was never seen in more than 1% of cultur ed lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disom y was identified in three cases. Mosaic trisomy 16 detected through amnioce ntesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in t he resolution of this abnormality. As 80% of these patients were ascertaine d because of the presence of abnormal levels of MSAFP or MShCG, the increas ed use of maternal serum screening should bring more such cases to clinical attention. Am. J. Med. Genet. 80:473-480, 1998. (C) 1998 Wiley-Liss, Inc.