- Numerical Chromosomal Aberrations.

Numerical Chromosomal Aberrations:

Aneuoploidy

A chromosome profile with fewer or greater than the normal diploid number where the total is not a multiple of 23.

n  If an extra chromosome is present (presence of three copies of the chromosome) : trisomy for that particular chromosome e.g. trisomy 21, trisomy 18, trisomy 13.

Trisomies are the most common numerical chromosomal anomalies found in humans.

Most autosomal aneuploidies are fatal in utero.

Three are survivable to term: Trisomy 13, 18 and 21.

Children with trisomy 21 (Down’s syndrome) are believed to have the most favorable outcome, as chromosome 21 has fewer genes than the other autosomes (it is short and has a low gene density)

Mechanism:  Non disjunction (Failure of the two chromosomes of one pair to disjoin).

n  If a chromosome is missing: monosomy for that chromosome e.g. Turnersyndrome (monosomy X chromosome).

Mechanism:

ü  Non-dysjunction.

ü  Anaphase lag; failure of the chromosome to move quickly to be incorporated in the daughter cell, so it will be lost. 

Polyploidy

The number is exact multiple of the haploid number (23=n)

n  Triploid: one additional set of chromosomes (69) chromosomes, i.e. three copies of each chromosome.

Due to failure of one maturation division either in sperm or ovum.

n  Tetraploid: two additional sets of chromosomes (92) chromosomes, i.e. four copies of each chromosome.

Due to failure of completion of 1^st division of the zygote, is incompatible with life.

Mosaicism

n  When an individual has two or more cell populations with a different chromosomal makeup.

n  Mechanism:

1. early post zygotic non-disjunction (non dysjunction in mitosis during embryogenesis)

2. or when aneuploidy is present from conception but some cells revert to a normal karyotype, for example by losing one copy of a trisomic chromosome – so-called trisomy rescue.

n  E.g Mosaic down (47/46) and Mosaic Turner (45/46)

Mosaicism should be suspected if clinical symptoms are milder than expected in a non-mosaic patient with the same chromosomal abnormality, or if the patient’s skin shows unusual pigmentation.

The prognosis is frequently better for a patient with mosaicism than for one with a corresponding chromosomal abnormality without mosaicism.

In general, the smaller the proportion of the abnormal cell line, the better the prognosis.