GENETICS Comparison of modes of ascertainment for mosaic vs complete trisomy 21 Eran Bornstein, MD; Erez Lenchner, MS; Alan Donnenfeld, MD; Sara Kapp, MS, CGC; Sean M. Keeler, MD; Michael Y. Divon, MD OBJECTIVE: We sought to compare the indications for amniocentesis leading to the detection of either mosaicism of trisomy 21 (mosaic- T21) or complete trisomy 21 (T21). STUDY DESIGN: A retrospective review of a large amniocentesis database (n = 494,163) was conducted. All specimens with mosaic-T21 (n = 124) were compared with a maternal age– matched group of T21 fetuses (n = 496). Samples with normal karyotypes were matched for maternal age and served as normal controls (n = 496). The  2 testing was used for statistical analysis. RESULTS: The presence of an abnormal first-trimester screen, abnormal sonographic findings, and specifically the single sonographic abnormali- ties of either a cystic hygroma or a cardiac anomaly were significantly less common in the mosaic-T21 as compared with the T21 group. There were no such differences between the mosaic-T21 and the normal control group. CONCLUSION: Fetuses with mosaic-T21, similar to those with normal karyotype, do not present with the same abnormal screening tests as fetuses with T21. Key words: Down syndrome, mosaic, prenatal diagnosis, trisomy 21 Cite this article as: Bornstein E, Lenchner E, Donnenfeld A, et al. Comparison of modes of ascertainment for mosaic vs complete trisomy 21. Am J Obstet Gynecol 2009;200:440.e1-440.e5. D own syndrome, the most com- monly identified cause of mental retardation, accounts for approximately 5500 annual live births in the United States. 1 The most common genetic aber- ration responsible for this syndrome is complete trisomy 21 (T21). Complete T21 is thought to account for up to 92- 95% of all Down syndrome pregnancies and is most frequently, but not exclu- sively, the result of a maternal meiotic nondisjunction event. 1-4 Unbalanced Robertsonian translocations account for 1-2% of Down syndrome cases. In about 2-4% of all Down syndrome infants, mo- saicism of T21 (mosaic-T21) is de- tected. 2,5-7 This less common form of Down syndrome is characterized by the presence of 2 distinct cell lines: an abnor- mal cell line with T21 and another cell line with a normal karyotype. Prenatal screening for Down syn- drome has been the subject of extensive research in the past 4 decades with recent advancements revolutionizing the abil- ity to screen for this condition. 8-25 Ini- tially, maternal age was the only known risk factor. Using advanced maternal age (AMA) ( 35 years) as the sole indica- tion for invasive prenatal testing resulted in a poor detection rate of approximately 30%. 8 Moreover, as the portion of ad- vanced age gravidas has tripled during the past 30 years, this practice currently results in a high false-positive rate of 15-20%. 26 Modifying the maternal age–related risk by the incorporation of up to 4 sec- ond-trimester maternal serum analytes (-human chorionic gonadotropin [hCG], -fetoprotein, unconjugated es- triol, and dimeric inhibin-A) resulted in a profound improvement. 9,10 This sec- ond-trimester maternal serum screen has been associated with a detection rate of up to 75% and an acceptable 5% false- positive rate. More recently, it has been shown that first-trimester Down syndrome detec- tion can be achieved by modifying the maternal age-related risk with measure- ment of the nuchal translucency com- bined with maternal serum levels of both pregnancy-associated plasma protein-A and -hCG. 11-13 This first-trimester screening test was consistently shown to improve the detection rate to approxi- mately 85% with a 5% false-positive rate. Moreover, several investigators demon- strated that a detection rate of  90% with a reduction of the false-positive rate to 3% is possible by combining the first- and the second-trimester screening tests (known as sequential, integrated, or con- tingent testing). 14-17 Experience gained from pediatric and pathologic observations of the charac- teristic phenotypic expressions found in neonates with Down syndrome has led to the extensive use of sonography for genetic screening. In addition to in- creased nuchal translucency, an absent From the Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology (Drs Bornstein and Keeler) and the Human Genetics Program (Ms Kapp), New York University School of Medicine; the Statistics and Mapping Laboratory, New York University (Mr Lenchner); and the Department of Obstetrics and Gynecology, Lenox Hill Hospital (Dr Divon), New York, NY, and Genzyme Genetics, Philadelphia, PA (Dr Donnenfeld). Presented at the 29th Annual Meeting of the Society for Maternal–Fetal Medicine, San Diego, CA, Jan. 26-31, 2009. Received Nov. 11, 2008; revised Dec. 29, 2008; accepted Jan. 20, 2009. Reprints not available from the authors. 0002-9378/$36.00 © 2009 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2009.01.017 Research www. AJOG.org 440.e1 American Journal of Obstetrics & Gynecology APRIL 2009