Chromosomal Abnormalities

A normal human somatic cell is diploid (2n), carrying 46 chromosomes arranged in 23 homologous pairs. Chromosomal disorders arise when this number or the internal structure of individual chromosomes is disrupted by an error during cell division — most commonly failure of sister chromatids or homologous chromosomes to separate correctly, a process called non-disjunction, which produces aneuploidy (a gain or loss of one or more whole chromosomes relative to the normal count). When a recognisable, recurring cluster of signs and symptoms results from a specific chromosomal error, the resulting clinical picture is called a syndrome. Down's syndrome, Turner's syndrome, Klinefelter's syndrome and Patau's syndrome — this chapter's four named examples — are all syndromes produced by ane …

Down's syndrome (trisomy 21) results from an extra copy of chromosome 21 — three copies instead of the normal pair. It is characterised by severe mental retardation, defective development of the central nervous system, increased separation between the eyes, a flattened nasal bridge, malformed ears, and a mouth that stays constantly open with the tongue protruding — a combination of features that makes Down's syndrome one of the most clinically recognisable chromosomal disorders.

Patau's syndrome (trisomy 13) results, analogously, from an extra copy of chromosome 13, again thought to arise from meiotic non-disjunction. It produces a considerably more severe clinical picture than Down's syndrome: multiple and severe body malformations together with profound mental deficiency, including an abnormally small head with small eyes, cleft palate, and malformation of the brain and internal organs. Both conditions illustrate the same underlying principle — that trisomy of an autosome disrupts developm …

Klinefelter's syndrome affects males and results from the presence of an extra X chromosome, giving a karyotype of 47,XXY (44 autosomes + XXY) instead of the normal 44 + XY. Affected individuals are usually sterile, tend to be tall with long limbs and an obese build, have a high-pitched voice, under-developed genitalia, and often show some breast development (gynaecomastia) — a set of features that reflects the disruptive effect of carrying two X chromosomes alongside a Y in a male body.

Turner's syndrome affects females and results from the loss of one X chromosome rather than a gain, giving a karyotype of 45,X (44 autosomes + a single X, written XO) instead of the normal 44 + XX. Affected individuals are sterile females of low stature, with a distinctive webbed neck, under-developed breasts, rudimentary (non-functional) gonads, and an absence of the menstrual cycle at puberty. Where Klinefelter's syndrome is caused by an extra sex chromosome, Turner's syndrome is caused …