Incidence and Types of Chromosome Abnormalities

Errors in meiosis, or in early cleavage divisions, occur with extraordinary frequency. At least 10–25% of all pregnancies, for example, involve chromosomally abnormal conceptions. A large proportion of these terminate in the earliest stages of pregnancy, many of which go unrecognized. Nevertheless, even among clinically recognized pregnancies, nearly 10% of fetuses are chromosomally unbalanced. For the three types of clinically recognized pregnancies—spontaneous abortions, stillbirths, and livebirths—the frequencies of different chromosomal abnormalities are summarized in Table 63-2. The most common abnormalities are numerical, involving fetuses with additional (trisomy) or missing (monosomy) chromosomes, or those with one (triploidy) or two (tetraploidy) additional sets of chromosomes. Structural chromosome abnormalities are much less common, although several of the most important clinical chromosomal disorders involve structural rearrangements (see below).

Table 63-2 Frequency and Distribution of Chromosome Abnormalities in Different Types of Clinically Recognizable Pregnancies

Frequency of Abnormality Chromosome Abnormality Spontaneous Abortion Stillbirth Livebirth Probability of Surviving to Term, % Trisomy, all 25.1 4.0 0.3 5  +13, 18, 21 4.5 2.7 0.14 15  +16 7.5 — — 0 Sex chromosome monosomy (45,X) 8.7 0.1 0.01 1 Triploidy 6.4 0.2 — 0 Tetraploidy 2.4 — — 0 Structural abnormality 2.0 0.8 0.3 45 Total abnormalities 50.0 5.1 0.6 5

By far the most common abnormality is trisomy, which is identified in ~25% of spontaneous abortions and 0.3% of newborns. Trisomies for all chromosomes have now been identified in embryos or fetuses, but there is considerable variation in frequency for various chromosomes. For example, trisomy 16 is extraordinarily common, accounting for about one-third of all trisomies in spontaneous abortions, whereas trisomies 1, 5, 11, and 19 have been identified less often. Available evidence suggests two reasons for this variation: (1) some chromosomes (e.g., chromosome 16) are more likely to segregate abnormally or undergo nondisjunction during meiosis than are others; and (2) the potential for development varies widely among different trisomic conditions, with some being eliminated very early in gestation, others surviving to the time of clinical pregnancy recognition, and some (e.g., trisomies 13, 18, and 21 and sex chromosome trisomies) being compatible with survival to term.

Reff:

Harrison's Internal Medicine > Chapter 63. Chromosome Disorders >