The Principles of Clinical Cytogenetics - Extra Materials - Springer

330 Solveig Pflueger
Table 8
Effect of Maternal Age
Maternal age No. % % %
(years) karyotyped abnormal trisomic nontrisomic
20 104 18.3 4.8 13.5
20–24 256 28.5 12.1 16.4
25–29 339 26.3 10.6 15.6
30–34 161 32.3 19.3 13.0
35–39 99 34.3 25.3 9.0
40+ 32 65.6 50.0 15.6
Source: Adapted from ref. 36.
inherent limitations based on the particular chromosome-specific probes utilized; only the specific
aneuploidies being probed for will be detected. Using FISH techniques, Miharu and colleagues analyzed
450,580 sperm from 9 fertile and 12 infertile men (32). Disomy for chromosomes 1, 16, X, and
Y ranged from 0.34% to 0.84% in infertile subjects and from 0.32% to 0.61% in fertile subjects.
Guttenbach and colleagues examined 16,127 sperm from 8 healthy donors for disomy of chromosome
18 and found a range of 0.25–0.5% (33). Examination of 76,253 sperm from 7 donors revealed
a range of 0.31–0.34% of disomy for chromosomes 3, 7, 10, 11, 17, and X (34). Although FISH
studies have inherent limitations, the data suggest that the rate of paternal meiotic nondisjunction
appears relatively constant for the various chromosomes studied.
Overall, maternal age is the best known predictor of risk for nondisjunctional events, in particular
those resulting from errors in meiosis I. The association between maternal age and risk for Down
syndrome has long been established, and risk for trisomic abortuses also increases with advancing
maternal age (19,35,36) (see Table 8).
Not all chromosomal trisomies appear to have the same association with maternal age. Warburton
et al. found that age-associated nondisjunction appeared to have a greater effect on the smaller chromosomes,
with mean maternal age increasing with decreasing size of the trisomic chromosome (22).
Susceptibility to nondisjunction might not be the same for all chromosomes, and recurrence risks
might be dependent on the particular chromosome involved in the trisomy, the parent contributing
the extra chromosome, and the background risk associated with maternal age. Regardless of the exact
risk, many couples who have experienced a trisomic conceptus find the availability of prenatal diagnosis
reassuring in planning subsequent gestations.
Sex Chromosome Aneuploidy
Sex chromosome aneuploidies are among the most common chromosomal abnormalities, both in
spontaneous pregnancy loss and in liveborn infants. By far the most frequent sex chromosome aneuploidy
at conception is 45,X, accounting for approximately 1–2% of clinically recognized pregnancies.
It is the single most frequent abnormal karyotype seen in spontaneous abortions. The vast
majority of monosomy X conceptuses terminate in miscarriage, less than 1% of affected pregnancies
surviving to term (18,37). The incidence of Turner syndrome in surviving pregnancies is approximately
1 in 1000 female live births. No 45,Y karyotypes have been reported. This is not an unexpected
finding, considering the important contributions of genes located on the X chromosome.
The three sex chromosome trisomies, 47,XXX, 47,XXY, and 47,XYY, are much less frequent
than monosomy X in spontaneous pregnancy loss, but are similar to monosomy X in frequency at
term, each affecting approximately 1 in 1000 infants of the appropriate sex. Affected infants with sex
chromosome trisomies are not usually markedly dysmorphic and are often not identified unless cytogenetic
studies are performed for other reasons. These conditions are frequently not recognized until
later in life when behavioral changes or, in the case of 47,XXY, infertility, might cause the patient to