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Trisomy 21


Introduction

Trisomy 21 (Down syndrome) is the most common trisomy in live-born infants and in spontaneous abortions. British physician John Langdon Down first described the syndrome in 1866. The chromosomal abnormality was discovered in 1959 by French geneticist Jerome Lejeune, and in 1961, the name Down syndrome was proposed by the editors of The Lancet .

Disorder

Definition

Trisomy 21, also called Down syndrome, results from three copies of chromosome 21, either the entire chromosome or the critical region. The syndrome has a distinctive phenotype.

Prevalence and Epidemiology

Trisomy 21 is the most common inherited cause of intellectual disability. About 0.45% of human conceptuses have trisomy 21. The incidence of Down syndrome in live births is between 1 : 319 and 1 : 1000, depending on the population. The risk of trisomy 21 increases with increasing maternal age and decreases with advancing gestation (because of pregnancy loss). Controversy exists about whether the incidence increases with advancing paternal age. Table 151.1 presents maternal and gestational age risks, demonstrating these changes.

TABLE 151.1
PREVALENCE OF TRISOMY 21 BY MATERNAL AGE AND GESTATIONAL AGE
From Snijders RJM, Sundberg K, Holzgreve W, et al. Maternal age- and gestation-specific risk for trisomy 21. Ultrasound Obstet Gynecol 13:167–170, 1999.
Maternal Age (y) GESTATIONAL AGE (WK)
10 12 14 16 20 40
20 1 : 983 1 : 1068 1 : 1140 1 : 1200 1 : 1295 1 : 1527
25 1 : 870 1 : 946 1 : 1009 1 : 1062 1 : 1147 1 : 1342
30 1 : 576 1 : 626 1 : 668 1 : 703 1 : 759 1 : 895
31 1 : 500 1 : 543 1 : 580 1 : 610 1 : 658 1 : 776
32 1 : 424 1 : 461 1 : 492 1 : 518 1 : 559 1 : 659
33 1 : 352 1 : 383 1 : 409 1 : 430 1 : 464 1 : 547
34 1 : 287 1 : 312 1 : 333 1 : 350 1 : 378 1 : 446
35 1 : 229 1 : 249 1 : 266 1 : 280 1 : 302 1 : 356
36 1 : 180 1 : 196 1 : 209 1 : 220 1 : 238 1 : 280
37 1 : 140 1 : 152 1 : 163 1 : 171 1 : 185 1 : 218
38 1 : 108 1 : 117 1 : 125 1 : 131 1 : 142 1 : 167
39 1 : 82 1 : 89 1 : 95 1 : 100 1: 108 1 : 128
40 1 : 62 1 : 68 1 : 72 1 : 76 1 : 82 1 : 97
41 1 : 47 1 : 51 1 : 54 1 : 57 1 : 62 1 : 73
42 1 : 35 1 : 38 1 : 41 1 : 43 1 : 46 1 : 55
43 1 : 26 1 : 29 1 : 30 1 : 32 1 : 35 1 : 41
44 1 : 20 1 : 21 1 : 23 1 : 24 1 : 26 1 :30
45 1 : 15 1 : 16 1 : 17 1 : 18 1 : 19 1 : 23

Etiology and Pathophysiology

Most cases of trisomy 21 are due to meiotic nondisjunction (95%), usually in the ovum. In the remaining 5% of cases, unbalanced translocation accounts for 3% to 4%, and mosaicism accounts for 1%. The additional copy of chromosome 21 presumably causes increased expression of many genes on the chromosome, and the imbalance in expression is thought to cause the various phenotypic expressions of the disorder.

Manifestations of Disease

Clinical Presentation

Clinical presentation of trisomy 21 may vary, but most cases have distinct ultrasound (US) features including major structural anomalies and minor (“soft”) markers of aneuploidy. Nearly half of fetuses with trisomy 21 have a cardiac defect (for example, ventricular septal defects, atrioventricular septal defects, and tetralogy of Fallot). Other major anomalies include duodenal atresia and tracheoesophageal fistula/esophageal atresia. Findings may include increased nuchal fold, cerebral ventriculomegaly, echogenic intracardiac focus, pyelectasis, echogenic bowel, enlarged cisterna magna, pericardial effusion, liver calcification, and digit anomalies (polydactyly, clinodactyly, sandal gap, and clubfoot). Hepatosplenomegaly and fetal hydrops may occur secondary to a leukemoid reaction.

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