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Trisomy 21 (Down Syndrome) is the most common chromosomal abnormality amongst livebirths, with an incidence of 1/800. It is estimated that 80% of all trisomy 21 pregnancies conceived end as spontaneous abortions or as stillbirths; approximately 2% of spontaneous abortions and 1% of stillbirths will have trisomy 21. Mosaicism for trisomy 21 can occur in one of the two parents in a small percentage of cases. Such couples would be expected to have an increased risk of having additional trisomy 21 offspring, although families with recurrent trisomy 21 are rare.

In general, the features of mosaic Down syndrome are similar to those of full Down syndrome but with a tendency to a milder features. However the effects can be quite varied depending on level and distribution of trisomic cells. Thus the affected individuals may range from completely normal to presenting the full expression of Down syndrome. Some difficulties in predicting outcome of prenatally diagnosed mosaicism are 1) most such pregnancies tend to be terminated and so true outcome is rarely known; 2) most mosaic Down syndrome that is ascertained postnatally is identified as a consequence of presenting the features of Down syndrome (and is thus biased to those with abnormal outcomes); 3) mosaic trisomy 21 in a 'normal' individual would rarely be identified (i.e. there would be no reason to examine the chromosomes in their blood/ or the abnormality could be missing from their blood cells).

Full (non-mosaic) trisomy 21 in the fetal period (>8 weeks developmental age) shares some of the phenotypic features seen in infants, including the dysmorphic facial features (though usually less distinctive), cardiac anomalies (characteristically atrioventricular canal defect), and duodenal atresia. Additionally, trisomy 21 fetuses may present with generalized edema (hydrops), the mechanism of which is unclear. Many of these abnormalities can be detected on ultrasound performed at 17-18 weeks gestation. Most infants and children with full (non-mosaic) trisomy 21 have a distinctive dysmorphic facial appearance with a flattened facial profile and occiput, flattened nasal bridge, upslanting palpebral fissures, and protruding tongue. They may also have single palmar (simian) creases, cardiac anomalies, and duodenal atresia. Children with trisomy 21 syndrome are mentally retarded. They are at increased risk for myeloproliferative disorders, including congenital leukemia (transient myeloproliferative disorder) and leukemia later in life. The risk of Alzheimer’s dementia is also increased, with onset much earlier than in the chromosomally normal population.

Trisomy 21 mosaicism detected on CVS

Sachs et al (1990) reported on 4 cases of trisomy 21 mosaicism detected on CVS. In these cases the percentage of abnormal cells measured on CVS direct studies ranged from 88-96%. All 4 pregnancies were terminated and mosaic trisomy 21 was confirmed in fetal fibroblasts.

Trisomy 21 mosaicism detected on amniocentesis

In a study of 97 cases (Wallerstein et al. 2000), indications for amniocentesis were : advanced maternal age (69 cases), abnormal serum screening with increased risk of Down Syndrome(19 cases), parental anxiety (4 cases), elevated alpha-feto protein in serum screen (3 cases), and a prior child with a chromosome abnormality (2 cases). In cases with greater than 50% trisomy 21 cells in amniotic fluid there was a 59% chance for abnormalities, as compared to 45% risk with less than 50% abnormal cell line.

  • Normal liveborns* - 7 (~17% abn cells)- only two followed beyond the newborn period (one to 3 months and one 12 months) with no abnormal findings
  • Normal abortus – 41 (~35% abn cells) – all TAs
  • Abnormal liveborns – 6 (~46% abn cells) – Down syndrome facies and associated findings (5 cases) and isolated congenital heart disease (1 case)
  • Abnormal abortus – 43 (~34% abn cells) – Down syndrome facies (18cases), multiple congenital anomalies (15 cases) intrauterine fetal demise (5 cases), IUGR (4 cases), isolated congenital heart disease (1 case)

In another study, of 66 cases with prenatal diagnosis of mosaic trisomy 21 only 25 had outcome data. 17 showed features compatible with trisomy 21 Down Syndrome(33).

*Possible long term complications of trisomy 21 in an otherwise 'normal' baby could include developmental delay, as well as possible increased risk for pediatric leukemia.

Trisomy 21 detected after birth

Low levels of trisomy 21 have been detected in phenotypically normal adults ascertained because of recurrent pregnancy loss or a trisomic pregnancy. Mosaic trisomy 21 has also been identified in children with features of Down syndrome.

For a good discussion of clinical features of mosaic Down syndrome see:

Uniparental Disomy (UPD 21)

Uniparental disomy for chromosome 21 is not thought to have any phenotypic effect.

Link to What is UPD?
Link to Maternal UPD 21
Link to Paternal UPD 21?

Internet Links


Beverstock GC, Hansson K, Helderman-van den Enden AT, Brocker-Vriends A, Klumper F, Bartelings M, Dobbe-van Meerendonk W, Roosmalen JV, Kolkman PH, Kanhai HH. (1998) A near false-negative finding of mosaic trisomy 21-a cautionary tale. Prenatal Diagnosis 18(7):742-6. PubMed

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

Puddy V, Lam BC, Tang M, Wong KY, Lam YH, Wong K, Yeung CY. (1999) Variable levels of mosaicism for trisomy 21 in a non-immune hydropic infant with chylothorax. Prenatal Diagnosis 19(8):764-6. PubMed

Sachs ES, Jahoda MG, Los FJ, Pijpers L, Reuss A, Wladimiroff JW. (1990) Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies. American Journal of Medical Genetics 37:268-71. PubMed

Wallerstein R, Yu MT, Neu RL, Benn P, Lee Bowen C, Crandall B, Disteche C, Donahue R, Harrison B, Hershey D, Higgins RR, Jenkins LS, Jackson-Cook C, Keitges E, Khodr G, Lin CC, Luthardt FW, Meisner L, Mengden G, Patil SR, Rodriguez M, Sciorra LJ, Shaffer LG, Stetten G, Van Dyke DL, Wang H. (2000) Common trisomy mosaicism diagnosed in amniocytes involving chromosomes 13, 18, 20 and 21: karyotype-phenotype correlations. Prenatal Diagnosis 20(2):103-22. PubMed

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