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Trisomy 16 is estimated to occur in more than 1% of clinically recognized pregnancies, making it the most commonly occurring trisomy in humans. Full trisomy 16 normally results in miscarriage in the first trimester of pregnancy. When trisomy 16 cells are found by chorionic villus sampling (CVS) or amniocentesis in a pregnancy with a normally developing embryo/fetus, it is virtually always mosaic. Most trisomy 16 mosaicism detected by CVS will not be confirmed in amniotic fluid (AF). However even when present in amniotic fluid, it is very rarely found in multiple fetal tissues. The trisomy 16 cells will typically be confined to, for example, just skin or lung. The trisomy is normally absent from blood samples and it is impossible to predict which tissues will be affected. As a consequence the abnormal cells will often not be confirmed in liveborn infants, even after a positive amniocentesis result. This does not mean they are not there, but the effects of low level trisomy in specific tissues is impossible to predict.

When trisomy 16 is detected on CVS or AF, serial ultrasounds are recommended. In addition, it is important for the mother to be monitored for hypertension.

Trisomy 16 detected on CVS and amniocentesis

Benn (1998) has summarized a large series of published cases of trisomy 16 ascertained on CVS or amniocentesis. Because of reporting biases, the frequency of adverse outcome in these reports is probably higher than in reality. In a similar summary of all cases reported in the literature (N=162) diagnosed on either CVS or amniocentesis, it was found that ~22% were electively terminated, ~17% ended in intrauterine or neonatal death and ~61% resulted in liveborn children surviving past the neonatal period (Yong et al. 2003). Thus, excluding terminations, 78% resulted in a live birth. The average gestational age at birth for live births that survived beyond the neonatal period was 36.07 +/- 3.4 weeks (mean +/- standard error), compared to 32.00 +/- 1.80 weeks for live births that ended in neonatal death (t = 3.03, df = 74, p = 0.002).

Based on these and other publications, further conclusions are:

  • In most cases of trisomy 16 detected on CVS, outcome will be good— even if 100% of cells analyzed in the placenta show the trisomy.
  • Adverse outcome is more common when trisomic cells are seen on amniocentesis than when they are not. However, there are reports of pregnancies with a completely normal outcome despite detection of trisomy 16 in amniotic fluid. In addition, it is possible for the fetus to have trisomic cells even if not observed in amniotic fluid.
  • The most common complication is IUGR and almost all cases are below the mean for birth weight (Yong et al. 2003). There is also a lesser but significant risk for fetal malformations (many of which are repairable and may not be a long term problem), maternal hypertension, and fetal or neonatal death. Fetal malformations showing significant association with trisomy 16 mosaicism in live-births include: Heart defects (VSD-16%; ASD 10%); hypospadias (7.6%). Some other malformations observed at higher rates include: two vessel cord; clinodactyly; and pulmonary hypoplasia. (Yong et al., 2003).
  • There is also an increased risk for pre-term delivery. 22% of cases first diagnosed on CVS and 63% of cases first diagnosed on amniocentesis were delivered prior to 37 weeks gestation.
  • The level of trisomy on direct CVS (cytotrophoblast) was associated with more severe intrauterine growth restriction and higher risk of malformation, while the level of trisomy on cultured CVS (chorionic villous stroma) was associated only with intrauterine growth restriction.
  • The presence (but not level) of trisomy on amniocentesis (amniotic fluid) was associated with both intrauterine growth restriction and malformation, while the presence of trisomy in the amniotic mesenchyme was associated only with intrauterine growth restriction. Sex of the fetus was not associated with any outcome variables, although there was an excess of females (sex ratio = 0.45) that may be explained by selection against male mosaic trisomy 16 embryos before the time of CVS (~9-12 weeks). Yong et al. 2003.
  • Ultrasound appears to yield the best information for predictive outcome, with the exception that most IUGR occurs in the third trimester and thus will not be detected on a detailed 18 week ultrasound. However, most cases with severe anomalies and fetal or neonatal death will show growth delay and/or other anomalies at this point in time.
  • Elevated MSAFP and/or hCG has been suggested to result in increased risk for an adverse perinatal outcome (Benn and Collins 1999).
  • Skewed X-chromosome inactivation in the diploid fetal tissues from trisomy 16 mosaic cases was also associated with poorer outcome (Penaherrera et al. 2001), although it was emphasized that it was unlikely this information could be used on a prenatal basis at this point in time.
  • Long-term follow-up (>1 year of age) was compiled on 36 cases of trisomy 16 mosaicism detected on CVS or AF (Langlois et al. submitted). Of 20 cases diagnosed on CVS but with a normal (N=19) or unknown (n=1) amniocentesis result, all showed normal development postnatally. Catch-up growth was noted in most cases which were IUGR (<-2 SD) in weight or length at birth. Of 16 cases diagnosed with trisomy 16 mosaicism on amniocentesis, 4 cases (25%) showed global developmental delay (we unfortunately have few details of the severity of this delay). The remaining 12 cases with normal development included cases with and without fetal malformation and with and without IUGR. However, all four cases with global developmental delay had MORE than 1 major malformation compared to 6 out of the 32 children (CVS and AF diagnosed mosaicism combined) in the group with normal development (p=0.004), as well as being IUGR at term. The finding of uniparental disomy was not associated with postnatal developmental delay. {Note: 3 of the above 4 cases with developmental delay were those published reported by Pletcher et al. 1994 and Hsu et al 1998; also the degree of delay could not be assessed with the information available}

Uniparental Disomy (UPD 16)

Practically all cases of trisomy 16 mosaicism arise from a trisomy rescue event. That is, an error in maternal meiosis leads to a trisomy 16 conceptus, with the diploid cell line arising during development through the mechanism of trisomic rescue. Thus approximately 1/3 of all cases are associated with UPD16 in the fetal cell line. As all cases of UPD 16 have been found in conjunction with trisomy 16 cells confined predominantly, but not always exclusively, in the placenta it has been difficult to determine if UPD16 itself has any affect on outcome. Fetuses with UPD16 do tend to be smaller at birth than fetuses with biparental inheritance (Robinson 1997, and Yong et al. 2002 in press). However, trisomy 16 in the placenta seems to have an adverse affect on growth even in the absence of UPD. As it is not clear that there are any long-term consequences due to the UPD16, it is currently not recommended to test for presence of UPD on a prenatal basis. Testing for research purposes only is available here in Vancouver, BC, Canada (See research link below).

Link to What is UPD?
Link to Maternal UPD 16 page
Link to Paternal UPD 16 page

Internet Links

  • Human Chromosome 16 - Provides links to gene maps, sequences, associated genetic disorders, nonhuman genetic models, identified genes, research efforts and laboratories, and other information as available. Links are very scientific.
  • HUGO Chromosome 16 - Chromosome 16 specific sites
  • Disorders of Chromosome 16 Foundation - The Foundation provides information, education, and support to families of children living with a chromosome 16 disorder and to expectant parents confronting a similar diagnosis.
  • RESEARCH on trisomy 16 mosaicism in Vancouver.


Astner A, Schwinger E, Caliebe A, Jonat W, Gembruch U. Sonographically detected fetal and placental abnormalities associated with trisomy 16 confined to the placenta. (1998) A case report and review of the literature. Prenatal Diagnosis 18(12):1308-15. PubMed

Benn P. (1998) Trisomy 16 and trisomy 16 Mosaicism: a review. American Journal Medical Genetics. 79(2):121-33. PubMed

Benn P. Collins R (1999) Abnormal maternal serum inhibin-A levels in trisomy 16 mosaic pregnancies. Am J Hum Genet Suppl. 65:A172.

Brandenburg H, Los FJ, Veld PI. (1996) Clinical significance of placenta-confined nonmosaic trisomy 16. American Journal of Obstetrics & Gynecology 174(5):1663-1664. PubMed

Devi AS, Velinov M, Kamath MV, Eisenfeld L, Neu R, Ciarleglio L, Greenstein R, Benn P. (1993) Variable clinical expression of mosaic trisomy 16 in the newborn infant. American Journal Medical Genetics. 47(2):294-8. PubMed

Garber A, Carlson D, Schreck R, Fischel-Ghodsian N, Hsu WT, Oeztas S, Pepkowitz S, Graham JM. (1994) Prenatal diagnosis and dysmorphic findings in mosaic trisomy 16. Prenatal Diagnosis 14(4):257-66. PubMed

Hsu LY, Yu MT, Neu RL, Van Dyke DL, Benn PA, Bradshaw CL, Shaffer LG, Higgins RR, Khodr GS, Morton CC, Wang H, Brothman AR, Chadwick D, Disteche CM, Jenkins LS, Kalousek DK, Pantzar TJ, Wyatt P. (1997) Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations. Prenatal Diagnosis 17(3):201-42. PubMed

Hsu WT, Shchepin DA, Mao R, Berry-Kravis E, Garber AP, Fischel-Ghodsian N, Falk RE, Carlson DE, Roeder ER, Leeth EA, Hajianpour MJ, Wang JC, Rosenblum-Vos LS, Bhatt SD, Karson EM, Hux CH, Trunca C, Bialer MG, Linn SK, Schreck RR. (1998) Mosaic trisomy 16 ascertained through amniocentesis: evaluation of 11 new cases. Am J Med Genet. Dec 28;80(5):473-80 PubMed

Johnson MP, Childs MD, Robichaux AG 3d, Isada NB, Pryde PG, Koppitch FC 3d, Evans MI. (1993) Viable pregnancies after diagnosis of trisomy 16 by CVS: lethal aneuploidy compartmentalized to the trophoblast. Fetal Diagn Therapy 8(2):102-8. PubMed

Johnson P, Duncan K, Blunt S, Bell G, Ali Z, Cox P, Moore GE. (2000) Apparent confined placental mosaicism of trisomy 16 and multiple fetal anomalies: case report. Prenatal Diagnosis 20(5):417-21. PubMed

Kalousek DK, Langlois S, Barrett I, Yam I, Wilson DR, Howard-Peebles PN, Johnson MP, Giorgiutti E. (1993) Uniparental disomy for chromosome 16 in humans. American Journal of Human Genetics. 52(1):8-16. PubMed

Kohlhase J, Janssen B, Weidenauer K, Harms K, Bartels I. (2000) First confirmed case with paternal uniparental disomy of chromosome 16. American Journal Medical Genetics 91(3):190-1. PubMed

Langlois S, Yong PJ, Yong SL, Barrett I, Kalousek DK, Miny P, Exeler R, Morris K, Robinson WP (submitted-2005) Post-natal follow-up of prenatally diagnosed trisomy 16 mosaicism

Ledbetter DH, Engel E. (1995) Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Human Molecular Genetics 4:1757-1764. PubMed

Lindor NM, Jalal SM, Thibodeau SN, Bonde D, Sauser KL, Karnes PS. (1993) Mosaic trisomy 16 in a thriving infant: maternal heterodisomy for chromosome 16. Clinical Genetics. 44(4):185-9. PubMed

Peñaherrera MS, Barrett IJ, Brown CJ, Langlois S, Yong S-L, Lewis S, Bruyère H, Howard-Peebles P, Kalousek DK, Robinson WP (2000) An association between skewed X-chromosome inactivation in diploid fetal tissues and abnormal outcome in mosaic trisomies predominantly confined to the placenta. Clin Genet 58(6):436-46. PubMed

Pletcher BA, Sanz MM, Schlessel JS, Kunaporn S, McKenna C, Bialer MG, Alonso ML, Zaslav AL, Brown WT, Ray JH. (1994) Postnatal confirmation of prenatally diagnosed trisomy 16 mosaicism in two phenotypically abnormal liveborns. Prenatal Diagnosis Oct;14(10):933-40. PubMed

Robinson WP, McFadden DE, Barrett IJ, Kuchinka B, et al. (2002) Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism. Prenal Diag 22: in press.

Schneider AS, Bischoff FZ, McCaskill C, Coady ML, Stopfer JE, Shaffer LG. (1996) Comprehensive 4-year follow-up on a case of maternal heterodisomy for chromosome 16. American Journal Medical Genetics. Dec 11;66(2):204-8.

Stavropoulos DJ, Bick D, Kalousek DK. (1998) Molecular cytogenetic detection of confined gonadal mosaicism in a conceptus with trisomy 16 placental mosaicism. American Journal of Human Genetics. Dec;63(6):1912-4. PubMed

Whiteford ML, Coutts J, Al-Roomi L, Mather A, Lowther G, Cooke A, Vaughan JI, Moore GE, Tolmie JL. (1995) Uniparental isodisomy for chromosome 16 in a growth-retarded infant with congenital heart disease. Prenatal Diagnosis 15:579-584. PubMed

Wolstenholme J. (1995) An audit of trisomy 16 in man. Prenatal Diagnosis Feb;15(2):109-21. PubMed

Wolstenholme J. (1996) Confined placental mosaicism for trisomies 2, 3, 7, 8, 9, 16, and 22: their incidence, likely origins, and mechanisms for cell lineage compartmentalization. Prenatal Diagnosis.16(6):511-24. PubMed

Yong PJ, Marion SA, Barrett IJ, Kalousek DK, Robinson WP (2002) Evidence for Imprinting on Chromosome 16: the effect of uniparental disomy on the outcome of mosaic trisomy 16 pregnancies. Am J Med Genet. Oct 1;112(2):123-32. Pubmed

Yong PJ, Barrett IJ, Kalousek DK, Robinson WP (2003) Clinical aspects, prenatal diagnosis and pathogenesis of trisomy 16 mosaicism. J Med Genet 40:175-82. Pubmed 

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