The field of clinical cytogenetics and the description of syndromes
caused by gross chromosomal abnormalities laid the foundation for
defining and delineating malformation syndromes. Chromosomal abnormalities
are detected in approximately 1 in 110 newborns and are the common
most single cause of mental retardation or developmental delay.1,2 The
common pediatric indications for a chromosome analysis include growth
retardation, neurologic impairment, neuropsychological dysfunction,
ambiguous genitalia, or multiple congenital anomalies. Clinical
cytogenetics also, in part, laid the foundation of the field of dysmorphology.
This chapter provides the principles of human cytogenetics.
Cytogenetics is a whole genome analysis involving the examination
of chromosomes from a tissue of interest to identify large-scale
genomic alterations. This occurs through the microscopic examination
of chromosomes arrested during the metaphase stage of cell division.
The chromosomes are treated with enzymes and chemicals to produce
characteristic light and dark patterns, called bands, along
the arms of the chromosomes. Each of the 46 chromosomes can then
be identified individually and organized into a karyogram (the
ordered display of chromosomes, eFig. 173.1) and
described as a karyotype (the nomenclature used to
describe the results of the chromosome analysis, described in more
Normal Giemsa-banded human male karyogram showing each
homologous chromosome pair aligned with each other.
The benefits of a chromosome analysis include visualization of
the entire genome on a cell-by-cell basis, which allows for the
nonselective identification of large-scale alterations in genome
structure, as well as detection of mosaicism (the presence of two
or more distinct cell populations within an individual). The limitations
of this technology include a limit to the size of a genomic abnormality
that can be detected. This limit of resolution is about 10 megabases
(Mb) but varies according to the region of the genome in which the
abnormality occurs and the quality of the chromosome preparations,
because abnormalities will be detected only if they alter the banding pattern.
Another limitation of a standard chromosome analysis is the need
for an actively growing source of cells. At the time of sample acquisition,
the majority of cells will not be in metaphase, and therefore, must
be cultured, often with chemicals that increase the number of cells
in metaphase at the time the cells are harvested and prepared for
analysis. As a result, cells that have been fixed or are no longer viable
cannot be analyzed with this technology.
Normally, each human has 46 chromosomes that are distributed
in 23 pairs, 22 pairs of autosomes and 1 pair of sex chromosomes
(XX in females and XY in males). Thus, each individual has two copies
of each chromosome (ie, diploid). A normal chromosome
constitution is termed the euploid state, whereas
an abnormal chromosome complement is called aneuploidy. The
autosomes are numbered 1 to 22, with the numbers assigned in descending