Chromosome abnormalities involve the gain, loss or rearrangement of visible amounts of genetic material.

Each of our chromosomes has a characteristic structure and displays a specific pattern of dark and light bands when stained with chemicals. These features are conserved in all human beings, making the different chromosomes easy to identify and distinguish from each other under a microscope. They define what is known as a normal karyotype - a normal set of chromosomes. Any deviation from the normal karyotype, in terms of chromosome number or structure, is known as a chromosome abnormality.

While some chromosome abnormalities are harmless variations, most are associated with clinical disorders of one kind or another. Half of all spontaneous abortions are due to chromosome abnormalities but the incidence in live births falls to less than 1 per cent.

Numerical abnormalities

The most severe disorders are caused by the loss or gain of whole chromosomes, since this can affect the copy number of hundreds or even thousands of genes. Few of these numerical abnormalities are compatible with full-term development since there is a gross imbalance of gene products. The loss of one chromosome in a pair (monosomy, one copy) or the gain of an extra chromosome (trisomy, three copies) generally results in spontaneous abortion.

A few numerical abnormalities support development to term either because the chromosome has relatively few genes (13, 18, 21, Y-chromosome) or because there is a natural mechanism to adjust gene dosage even in normal people (X-chromosome). The most common numerical abnormalities are listed in Table 1.

Structural abnormalities

Structural abnormalities can be unbalanced or balanced. The former are similar to numerical abnormalities in that genetic material is either gained or lost. The abnormalities range from the loss or duplication of whole chromosome arms to the deletion or duplication of tiny chromosome fragments barely visible under the microscope. However, even these tiny deviations (microdeletions and microduplications) can encompass several to many genes and have severe effects. Table 2 lists some common deletion and microdeletion syndromes.

Balanced structural abnormalities involve the rearrangement of genetic material but no overall gain or loss. Examples include inversions (where a segment is removed from a chromosome, turned on its axis and sealed back in place), translocations (where part of one chromosome becomes attached to another) and ring chromosomes (where the ends of the long and short arms fuse together to form a circle).

Balanced abnormalities can have an immediate effect if a gene is disrupted by the breakpoint, if two genes are fused together, or if the relocation of a gene causes it to be expressed at a higher or lower level than usual. However, the major consequence is to prevent normal chromosome pairing at meiosis, leading to the production of sperm and eggs with incomplete or partially duplicated chromosome sets.