The Principles of Clinical Cytogenetics - Extra Materials - Springer

Autosomal Aneuploidy 133
INTRODUCTION
From: The Principles of Clinical Cytogenetics, Second Edition
Edited by: S. L. Gersen and M. B. Keagle © Humana Press Inc., Totowa, NJ
133
8
Autosomal Aneuploidy
Jin-Chen C. Wang, MD
The term aneuploidy refers to cytogenetic abnormalities in which all or part of one or more chromosomes
is added or deleted. Autosomal aneuploidy refers to all such abnormalities that do not
involve the sex chromosomes. These can be either numerical (the topic of this chapter) or structural,
the vast majority being trisomies, and can be present only in some cells (mosaic aneuploidy) or in all
cells (nonmosaic). The incidence of autosomal aneuploidy in newborns is estimated to be 0.2% (1).
Many autosomal aneuploidies are incompatible with fetal survival and, therefore, have much higher
incidences (approximately 27–30%) in spontaneous abortuses (2–4). These are discussed below and
covered in detail in Chapter 12.
Cytogenetic studies of human oöcytes and sperm reveal that the overall frequency of abnormalities
is approximately 20% and 10%, respectively (reviewed in ref. 5). More than 90% of the abnormalities
observed in oöcytes and less than 50% of those seen in sperm are numerical. Studies using
fluorescence in situ hybridization (FISH) (6) or primed in situ labeling (PRINS) (7,8), which do not
require the presence of dividing cells, have shown that the frequency of autosomal aneuploidy in
human sperm is relatively uniform for all chromosomes studied (chromosomes 3, 7, 8, 9, 10, 11, 13,
16, 17, and 21), with a range of 0.26–0.34%. On the other hand, one study using FISH (9) reported a
higher frequency of aneuploidy for chromosome 21 (0.29%) than for other chromosomes studied
(0.08–0.19% for chromosomes 1, 2, 4, 9, 12, 15, 16, 18, and 20). It is therefore possible that meiotic
nondisjunction is random for all autosomes, with the possible exception of chromosome 21. However,
this is not the case for aneuploidy actually observed in spontaneous abortuses or liveborns.
Trisomies for all autosomes have been reported in spontaneous abortuses (3,10,11), including
trisomy 1, which has been reported in a clinically recognized pregnancy at 8–9 weeks of gestation
(11) and in a clinically recognized in vitro fertilization (IVF) pregnancy at 6 weeks of gestation (12).
However, no fetal pole ever developed in either case. The observed frequency of each trisomy, however,
varies greatly. For example, trisomy 16 accounts for approximately 30% of all autosomal trisomies
in abortuses (3). In liveborns, the only trisomies that have not been reported in either mosaic or
nonmosaic form are those involving chromosomes 1 and 11, although trisomies other than 13, 18,
and 21 are rare. Autosomal monosomies, on the other hand, are extremely rare in both liveborns and
recognized abortuses.
The supposition that, with the probable exception of trisomy 21, the frequencies of trisomy for
each chromosome might be similar at the time of conception but differ greatly among abortuses and
liveborns can be explained by the devastating effect of chromosomal imbalance. Many autosomal
aneuploidies are so deleterious that they are lethal in the pre-embryonic stage and thus result in
unrecognized and, therefore, unstudied spontaneous abortions. The lethality of a particular autosomal
aneuploidy correlates with the gene content of the chromosome involved (10). Aneuploidies for