he risk of any autosomal trisomy rises steeply with maternal age, particularly after age 35 (Fig. 13-2). Oocytes are suspended in midprophase of meiosis I from birth until ovulation, in some cases for 50 years. Following completion of meiosis at ovulation, nondisjunction results in one gamete having two copies of the afected chromosome, leading to trisomy if fertilized. he other gamete, receiving no copy of the afected chromosome, will be monosomic if fertilized. It is estimated that 10 to 20 percent of oocytes are aneuploid secondary to meiotic errors, compared with 3 to 4 percent of sperm. lthough each chromosome pair is equally likely to have a segregation error, programs in the United States, 2006-2010, which included live it is rare for trisomies other than 21, 18, or 13 to result in a births, stillbirths, and pregnancy terminations. (Data from Mai, 2013. term pregnancy, and most fetuses with trisomies 18 and 13 die Redrawn with permission from Dashe JS: Aneuploidy screening. before term. Obstet GynecoIo128(1):181, 2016.) 6 10 11'.13 14 16 19
FIGURE 13-3 Abnormal male karyotype with trisomy 21, consistent with Down syndrome (47,XY,+21). (Used with permission from
Dr. Frederick Elder.)
Mter a pregnancy with an autosomal trisomy, the risk for any autosomal trisomy in a future pregnancy approximates 1 percent until the woman's age-related risk exceeds this. Accordingly, prenatal diagnosis with chorionic villus sampling or amniocentesis is ofered in these subsequent pregnancies (Chap. 14, p. 292). Parental chromosomal studies are not indicated unless the afected pregnancy was caused by an unbalanced translocation or other structural rearrangement.
Trisomy 21-Down Syndrome. In 1866, ]. L. H. Down described a group of intellectually disabled children with distinctive physical features. Nearly 100 years later, Lejeune (1959) demonstrated that Down syndrome is caused by an autosomal trisomy (Fig. 13-3). Trisomy 21 causes 95 percent of Down syndrome cases, whereas 3 to 4 percent of cases are due to a robertsonian translocation, described later (p. 262). he remaining 1 to 2 percent results from an isochromosome or from mosaicism. he nondisjunction that yields trisomy 21 occurs during meiosis I in approximately 75 percent of cases, and the remaining events are during meiosis II.
Down syndrome is the most common nonlethal trisomy.
Its approximate prevalence is 1 in 500 recognized pregnancies. However, fetal losses and pregnancy terminations yield an estimated prevalence of 13.5 in 10,000 births in the United States-1 per 740 (Mai, 2013; Parker, 2010). he fetal death rate beyond 20 weeks' gestation approximates 5 percent (Loane, 2013). Coinciding with the older maternal age distribution during the past four decades, the prevalence of Down syndrome has risen approximately 33 percent (Loane, 2013; Parker, 2010; Shin, 2009).
Notably, adult women with Down syndrome are fertile, and a third of their ofspring will have Down syndrome (Scharrer, 1975). Males with Down syndrome are almost always sterile because of markedly reduced spermatogenesis.