Page 273 - Textbook of Pathology, 6th Edition

and Herpes simplex) during pregnancy is associated with 257
multisystem anomalies and TORCH syndrome in the
newborn (page 191).
6. Congenital syphilis. As discussed in Chapter 6, vertical
transmission of syphilis from mother to foetus is
characterised by Hutchinson’s triad: interstitial keratitis, CHAPTER 10
sensorineural deafness and deformed Hutchinson’s teeth,
along with saddle-nose deformity.

CYTOGENETIC (KARYOTYPIC)
ABNORMALITIES

Human germ cells (ova and sperms) contain 23 chromo-
somes (haploid or 1N) while all the nucleated somatic cells
of the human body contain 23 pairs of chromosomes
(diploid or 2N)—44 autosomes and 2 sex chromosomes,
being XX in females (46, XX) and XY in males (46, XY). The
branch of science dealing with the study of human Genetic and Paediatric Diseases
chromosomal abnormalities is called cytogenetics Figure 10.1 Nuclear sexing. A, sex chromatin as seen in scraped
squamous cells from oral cavity. B, Barr body seen as drumstick
(discussed in Chapter 2). appendage attached to a lobe of a circulating neutrophil.
In a female, one of the two X chromosomes (paternal or
maternal derived) is inactivated during embryogenesis as
stated in Lyon hypothesis. This inactivation is passed to all Based on length of chromosomes, they are divided into 7
the somatic cells while the germ cells in the female remain groups—A to G, called Denver classification adopted at a
unaffected i.e. ovary will always have active X chromosome. meeting in Denver, Colorado in US.
Such an inactive X chromosome in the somatic cells in females Chromosomal banding techniques are employed for study
lies condensed in the nucleus and is called as sex chromatin of classes of chromosomes. Chromosomal bands are unique
alternate dark and light staining patterns. Banding techniques
seen specifically in the somatic cells in females. Nuclear sexing
can be done for genetic female testing by preparing and include:
staining the smears of squamous cells scraped from oral i) G-banding (Giemsa stain);
cavity, or by identifying the Barr body in the circulating ii) Q-banding (quinacrine fluorescence stain);
neutrophils as drumstick appendage attached to one of the iii) R-banding (reverse Giemsa staining); and
nuclear lobes (Fig. 10.1). A minimum of 30% cells positive iv) C-banding (constitutive heterochromatin demonstration).
for sex chromatin is indicative of genetically female With these brief introductory comments, we can now turn
composition. to abnormalities of chromosomes which can be divided into
2 types:
Though chromosomes can be studied in any human 1. Numerical abnormalities; and
nucleated cells, circulating lymphocytes are more often used 2. Structural abnormalities.
for this purpose. The study is done by arresting the dividing
cells in metaphase by colchicine and then spreading them Numerical Abnormalities
on glass slide and staining them with Giemsa stain.
Karyotype is the photographic representation of the As mentioned above, normal karyotype of a human
stained preparation of chromosomes. nucleated somatic cell is diploid or 2N (46 chromosomes)
Each chromosome is composed of a pair of identical
double helix of chromosomal DNA called chromatids. The
chromosomes are classified based on their length and location
of the centromere; centromere is the point where the two
chromatids cross each other (Fig. 10.2). The distal end of each
chromosome is called telomere.
Based on centromeric location, they are classified into 3
groups:
Metacentric chromosomes (numbers 1, 3, 16, 19, 20) are those
in which the centromere is exactly in the middle.
Submetacentric chromosomes (numbers 1, 3) in which the
centromere divides the chromosomes into short arm (p arm;
petit means short in French) and long arm (q arm; for alphabet
next to p).
Acrocentric chromosomes (numbers 13, 14, 15, 21, 22, and
Y) have very short arm and the centromere is eccentrically Figure 10.2 Classification of chromosomes based on size and
located. location of centromere.