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1994-07-10-18 Trisomy 22, placenta © Thomas
Trisomy 22, placenta

Dominique Thomas, MD, Michel Bossens, MD, Margarida Freund, MD, Ernesto Camacho, MD, Christine Müller, MD

Address correspondence to Dominique Thomas, MD, Département de Gynécologie-Obstétrique. Centre Hospitalier Etterbeek Ixelles, rue J. Paquot 63, 1050 Bruxelles, Belgium. Ph: 32-2-641-4111, Fax: 32-2-647-4732

Synonyms: Fetal-placental dyscrepancy, trisomy 22.


Definition: Placental aneuploïdy associated with a normal fetal karyotype on amniocytes and on lymphocytes.

Prevalence: Unknown. Very few cases of such an abnormality are described in the literature. The prevalence of mosaicism, which is a similar abnormality, is evaluated between 60-150:10,000 for all chorionic villus sampling1,2.

Etiology: A mitotic non-disjunction was proposed by Crane and Cheung3 at the morula stage before the differentiation of the inner cell mass. Another possible etiology is a trisomic conceptus followed by the loss of one extra chromosome4.

Associated abnormality: Thick placenta, intrauterine growth retardation (IUGR) are associated with this case of placental aneuploidy.

Prognosis: Acute fetal distress occurred in the third trimester.

Management: Fetal extraction by cesarean section is needed after clinical demonstration of placental insufficiency.

MESH BDE MIM POS ICD9 758.5 CDC 758.520


The last ten years of chorionic villi sampling (CVS) for cytogenetic studies have led to the knowledge of cytogenetic discrepancies between chorionic villi and fetal tissues5,6. Mosaicism may be found in the cytotrophoblast, in the mesenchymal cells culture or in both with a normal fetal karyotype (amniocytes and fetal lymphocytes). More recently, several reports have also pointed out the possibility of the coexistence of mosaicism of a chromosome aneuploidy in the placenta and in the fetus, but not for all tissues (example: mosaicism for trisomy 5 in chorionic villi sampling, amniocytes and fibroblasts of the diaphragm and normal karyotype in the lymphocytes7).

Placental mosaicism confined to the placenta does not necessarily lead to an abnormal pregnancy but can be responsible for an IUGR, especially if confirmed on placental tissue after delivery8.

Case report

A 31-year-old G2P1 was referred to our antenatal diagnostic unit because of metrorrhagia. This problem began at 10 weeks of amenorrhea and continued with little importance until the 32nd week. Her past obstetrical history consisted of a normal full-term pregnancy and birth of a 3100g normal healthy baby. The maternal blood tests were normal throughout the pregnancy. Serological and hypertensive markers, as well as maternal alpha-fetoprotein, remained normal. Her prenatal course up to 25 weeks, except for metrorrhagia, was uneventful.

Serial ultrasound examinations were performed with a Toshiba 100 scanner. Normal fetal morphology was visualized. We noted the existence of a number of large echo-free areas continued in the basal plate. These remained unchanged between the examinations until 32-33 weeks (fig. 1,2). Acoustic changes occurred at the last sonographic examination and we observed echogenic areas in the placenta and the basal plate.

Figure 1: Thick placenta containing large echo-free areas.
Figure 2: Stable sonographic aspect of the placenta between two examinations.

The biometry revealed a growth retardation of the biparietal diameter, and abdominal transversal diameter after 25 weeks until the end of the pregnancy (fig. 3,4).

Figure 3: Biparietal growth curve showing IUGR after week 30.

Figure 4: Transverse abdominal diameter curve showing IUGR after week 25.

An enlarged placenta appeared after 25 weeks and was found at each ultrasound examination. The thickness of the placenta exceeded 50 mm at the insertion of the umbilical cord.

Considering the abnormal aspect of the placenta and the fetal growth retardation, we suggested that the patient undergo a chromosomal study. At the end of the 30th weeks, we performed a trans- abdominal chorionic villous sampling, an amniocentesis and a fetal blood sampling.

Results are summarized in the top part of Table 1. Around 34 weeks, we noticed a mild increase in the resistive index (RI) in the umbilical artery, while the RI in the middle cerebral arteries was under the 10th percentile. At the same time, the non-stress test became abnormal with decelerations simultaneous to spontaneous contractions.

It was decided to opt for an early delivery. A 1690g boy was delivered by cesarean section. The Apgar score was 9/10. At the age of 24 months, the morphological and neurological developments were normal, a mild growth retardation persisted, the weight being 11 kg (p<10).

The chromosomal study at birth confirmed the placental aneuploidy and a normal fetal karyotype (Table 1, low portion). The microscopic examination (fig. 5) of the placenta showed recent retroplacental hematoma and small, retracted placental villi in a large intervillous chamber.

Table 1: Antenatal and postnatal karyotypes




Number of mitosis


Chorionic villi sampling

Amniotic fluid


47, XY, + 22 direct

46, XY

46, XY





Chorionic membranes

Placental biopsy


46, XY

47, XY, + 22 culture

46, XY




Figure 5: Microscopic examination of the placenta: retracted villi in a large intervillous chamber.


Ultrasound diagnosis

Aneuploidy confined to the placenta in this case appears as an enlargement of the placenta containing many sonolucent areas. A previous case report on the same type of abnormality presented similar features with apparent placental abnormalities associated with intrauterine growth retardation9.

We believe that abnormal microscopic arrangement of the placental villi in the intervillous chamber may cause this abnormal ultrasound aspect of the placenta.

Dombrowski et al.10 studied thick placentas and found an incidence of 0.6% among ultrasound recordings of 18,827 viable pregnancies. In the group of pregnancies with a thick placenta, perinatal mortality, rate of abruptio placentae, neonatal intensive care unit admissions and abnormalities have significantly increased. The possible etiologies were studied, and 71 out of 83 turned out to be idiopathic. Some of the cases classified as idiopathic may well be placental aneuploidy, therefore we advocated placental cytogenetic study.

By placental transabdominal biopsy in the third trimester of pregnancy, a karyotype can be obtained in over 90% of the cases within 48 hours11. It is a safe procedure which is less invasive than cordocentesis and can be a first diagnostic approach.

Avillous spaces or placental caverns are also called "placental lakes". Many descriptions of this placental abnormality have been made. Large echo-free spaces can be found under chorionic plate near umbilical insertion or in the marginal zone and within the placental tissue in the second part of the pregnancy. Smaller spaces have been described in the center of the cotyledon in the third trimester. Most of them have no pathological consequence12. Our present description of stable echo- free intraplacental areas may be compared to the description by Jauniaux et al. of thick placenta with large echo-free spaces, fetal growth retardation and premature delivery13.


One model to explain discrepancies between the embryo and placenta was proposed by Crane and Cheung in 19883. They described three types of discrepancies between direct preparation, long- term culture and fetus (fig. 6).

Figure 6: Model explaining cytogenetic inconsistencies proposed by Crane and Cheung. Three examples of accidents to explain discrepancies between fetal karyotypes and placenta (direct preparation and villus culture).

g accident 1 (arrow 1): the direct preparation disagrees with villus and fetal cultures: mosaicism confined to the direct preparation.

g accident 2 (arrow 2): the fetal culture and cultured villi disagree with the direct preparation: normal cell lines in direct chromosome preparation associated with aneuplody in fetus and villus culture.

g accident 3 (arrow 3): the fetal culture and villus culture disagree with direct preparation: a single cell line in direct chromosome preparation with mosaicism in cultured villi and fetal tissue.

A mitotic non-disjunction at the morula stage before the differentiation of the inner cell mass (arrow 1, fig. 6) could explain the cases where direct preparation of trophoblast (mitotic cells issued from cytotrophoblast) shows chromosomal abnormality.

When the chromosomal abnormality is also found in long-term culture (arrows 2 and 3), this abnormality might be found in certain fetal tissues. Long-term culture cells come from the mesenchymal core, which is extra embryonic mesoderm and is derived from the inner cell mass as is the fetus.

Abnormal chorionic villi sampling karyotype in both direct and long-term culture could also be due to the puncture of a placenta from a vanishing abnormal twin14.

Another model presented recently by Morichon-Delvalley15 in a case of trisomy 15 involving chorionic-villi associated with Prader-Willi syndrome at birth might be the presence of a trisomic conceptus associated with the loss of one of the extra chromosomes in the fetus, with a one third risk of uniparental disomy for the originally affected chromosomal pair. The study on the molecular biological bases has not yet been carried out in our case.

Associated abnormalities

A review of 39 pregnancies in which chorionic villi sampling showed Level II or Level III mosaicism was published by Fryburg et al.16. In the cases in which the pregnancy continued (without fetal chromosomal abnormality), they failed to show a difference in the incidence of pregnancy loss, congenital malformation, or developmental delay in the infants, compared to a control group with chorionic villi sampling normal karyotypes. They found an increased incidence of IUGR in Level III mosaicism.

Level I pseudomosaicism refers to single cell abnormalities. In Level II mosaicism or Type II pseudo-mosaicism, mosaicism is detected in two or more cells from only one culture vessel. Type III or true mosaicism is defined as the presence of two or more cell lines recovered from more than one culture vessel.

In 1991, Kalousek et al.17 found an association of IUGR and fetal demise when an abnormal cell line was still detectable in term placenta. In 1992, William III et al.9 and Post et al.18 published two case reports of IUGR associated with trisomy 16 confined to the placenta. However, in a prospective study of 71 cytogenetic evaluations of placentas derived from growth-retarded newborns, Kennerknecht et al.19 did not show any case of true confined placental mosaicism.


Isolated placental thickness is associated with a bad fetal and neonatal prognosis. A thick placenta with large echo-free areas associated to IUGR with or without increased maternal alpha-fetoprotein should lead us to suspect a chromosomal anomaly confined to the placenta. A transabdominal chorionic villi sampling is indicated. The possibility exists of overlooking such an anomaly if the karyotype is studied only on the fetal cells (amniocytes, fetal lymphocytes). Even when the fetal karyotype is apparently normal, the loss of one of the chromosomes of a trisomic conceptus is not excluded, uniparental disomy having been shown in some patients. In this case, as well as in the case of true mosaicism confined to the placenta, we should expect a third trimester placental insufficiency.


The authors would like to thank Mr. Barry J. Hallinan for correcting the English text.


1. Fryburg JS, Dimaio MS, Yang-Feng TL, et al.: Follow up of pregnancies complicated by placental mosaicism diagnosed by chorionic villous sampling. Prenat Diagn 13:481-494, 1993.

2. Verjerslev LO, Mikelsen M: The European collaborative study on mosaicism in chorionic villous sampling: Data from 1986 to 1987. Prenat Diagn 9:575-588, 1989.

3. Crane JP, Cheung SW: An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue. Prenat Diagn 8:119-129, 1988.

4. Spence JE, Perciaccante RG, Grieg MG, et al.: Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet 42:217-226, 1988.

5. Kalousek DK, Dill FJ: Chromosomal mosaicism confined to the placenta in human conceptions. Science 221:665-667, 1983.

6. Simoni G, Gimelii G, Luco C, et al.: Discordance between prenatal cytogenetic diagnosis after chorionic villi sampling and chromosomal constitution of the fetus. In Fraccaro M,Simoni G, Brambati B, (Eds) First trimester fetal diagnosis p137-143, Springer-Verlag, Berlin, 1985.

7. Sciorra LJ, Hux C, Day Salvadore D, et al.: Trisomy 5 mosaicism detected prenatally with an affected liveborn. Prenat Diagn 12:477-482, 1992.

8. Kalousek DK, Howard-Peebles PN, Olson SB, et al.: Confirmation of chorionic villi sampling mosaicism in term placentas and high frequency of intrauterine growth retardation: Association with confined placental mosaicism. Prenat Diagn 11: 743-750, 1991.

9. Williams III J, Wancy BB, Rubin CH, et al.: Apparent non mosaic trisomy 16 in chorionic villi: Diagnostic dilema or clinically significant finding? Prenat Diagn 12:163-168, 1992.

10. Dombrowski MP, Wolfe HM, Saleh A, et al.: The sonographically thick placenta: A predictor of increased perinatal morbidity and mortality. Ultrasound Obstet Gynecol 2:252-255, 1992.

11. Constantine G, Fowlie A, Pearson J: Placental biopsy in the third trimester of pregnancy. Prenat Diagn 12:783-788, 1992.

12. Jauniaux E, Campbell S: Placenta and cord in ultrasound in obstetrics and gynecology. Dewbury K, Meire H, Cosgrove D, Livingstone C , Chap.23, 443-444, Edinburgh, 1993.

13. Jauniaux E, Moscoso G, Campbell S, et al.: Correlation of ultrasound and pathologic findings of placental anomalies in pregnancies with elevated maternal serum alpha-fetoprotein. Eur J ObstetGynecol Reprod Biol 37:219-230, 1990.

14. Tharapel AT, Elias S, Shulman LP, et al.: Resorbed co-twin as an explanation for discrepant chorionic villus results: Non mosaic 47, XX, +16 villi (direct and culture) with normal (46, XX) amniotic fluid and neonatal blood. Prenat Diagn 9: 467-472, 1989.

15. Morichon-Delvallez N, Mussat P, Dumez Y, et al.: Trisomy 15 in chorionic villi and Prader-Willy syndrome at birth. Prenat Diagn 13:307-308, 1993.

16. Fryburg JS, Dimaio MS, Yang-Feng TL, et al.: Follow-up of pregnancies complicated by placental mosaicism diagnosed by chorionic villous sampling. Prenat Diagn 13:481-494, 1993.

17. Kalousek DK, Howard-Peebles PN, Olson SB, et al.: Confirmation of chorionic villi sampling mosaicism in term placentas and high frequency of intrauterine growth retardation: Association with confined placental mosaicism. Prenat Diagn 11: 743-750, 1991.

18. Post JG, Nijhuis JG: Trisomy 16 confined to the placenta. Prenat Diagn 12:1001-1007, 1992.

19. Kennerknecht I, Krämer S, Grab D, et al.: A prospective cytogenetic study of third-trimester placentas in small-for-date but otherwise normal newborns. Prenat Diagn 13:257-269, 1993.

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