Page 274 - Textbook of Pathology, 6th Edition

258 while the germ cells have haploid or 1N (23 chromo- Three clinically important syndromes resulting from
somes). numerical aberrations of chromosomes due to nondisjunction
1. Polyploidy is the term used for the number of chromo- are as under and their main clinical features are illustrated
somes which is a multiple of haploid number e.g. triploid or in Fig. 10.3:
3N (69 chromosomes), tetraploid or 4N (92 chromosomes). Down’s syndrome. There is trisomy 21 in about 95% cases
Polyploidy occurs normally in megakaryocytes and dividing of Down’s syndrome due to nondisjunction during meiosis
liver cells. Polyploidy in somatic cells of conceptus results in one of the parents. Down’s syndrome is the most common
in spontaneous abortions. chromosomal disorder and is the commonest cause of mental
retardation. The incidence of producing offspring with
2. Aneuploidy is the number of chromosomes which is not Down’s syndrome rises in mothers over 35 years of age.
SECTION I
an exact multiple of haploid number e.g. hypodiploid or Klinefelter’s syndrome. Klinefelter’s syndrome is the
2N-1 (45 chromosomes) monosomy, hyperdiploid or 2 N+1 most important example of sex chromosome trisomy. About
(47 chromosomes) trisomy. 80% cases have 47, XXY karyotype while others are mosaics.
The most common mechanism of aneuploidy is Typically, these patients have testicular dysgenesis. In
nondisjunction. Nondisjunction is the failure of chromo- general, sex chromosome trisomies are more common than
somes to separate normally during cell division during first trisomies of autosomes.
or second stage of meiosis, or in mitosis. Turner’s syndrome. Turner’s syndrome is an example
Nondisjunction during first meiotic division stage will result of monosomy (45, X0) most often due to loss of X
in two gametes from both the parental chromosomes due to chromosome in paternal meiosis.
failure to separate while the other two gametes will have no
chromosomes (nullisomic).
Nondisjunction during second meiotic division stage results Structural Abnormalities
in one gamete with two identical copies of the same During cell division (meiosis as well as mitosis), certain
chromosome, one nullisomic gamete, and two gametes with structural abnormalities of chromosomes may appear. These
normal chromosome number. may occur during gametogenesis and then transmitted to
Nondisjunction during mitosis results in mosaicism, all somatic cells and cause hereditary transmissible disorders,
meaning thereby that the individual has two or more types or may produce somatic cell mutations and result in changes
of cell lines derived from the same zygote. Mosaicism of varying from no effect to some forms of cancers. Structural
mitotic nondisjunction of chromosomes occurs in cancers. abnormalities may be balanced or unbalanced.
Anaphase lag is a form of nondisjunction involving single Balanced structural alteration means no change in total
pair of chromosomes in which one chromosome in meiosis number of genes or genetic material.
General Pathology and Basic Techniques
or a chromatid in mitosis fails to reach the pole of dividing Unbalanced structural alteration refers to gene rearrange-
cell at the same time (i.e. it lags behind) and is left out of the ment resulting in loss or gain of genetic material.
nucleus of daughter cell. This results in one normal daughter Some common forms of structural abnormalities are as
cell and the other monosomic for the missing chromosome. under (Fig. 10.4):

Figure 10.3 Clinical features of important forms of numerical chromosomal abnormalities.