Disorders of the Sex Chromosomes

Disorders of the sex chromosome (like disorders of the autosomes) can be either numerical or structural, and can be present in all cells or in a mosaic form. Clinical indications that should raise suspicions of a sex chromosome abnormality are:
 * delay in onset of puberty;
 * primary or secondary amenorrhea;
 * infertility;
 * ambiguous genitalia.

These disorders are considered very common with incidence of about 1:400–500. Phenotypes associated with sex chromosome disorders are less severe than autosomal defects and this is mainly due to X chromosome inactivation, as well as the fact that Y chromosomes have a low gene content. X chromosome inactivation is the the process by which most genes on one of the two X chromosomes in females are silenced epigenetically and randomly, and so fail to produce any product. In somatic cells in normal females (but not in normal males), one X chromosome is inactivated early in development, thus equalizing the expression of X-linked genes in the 2 sexes. Thus females are mosaic with respect to X-linked gene expression.

Triple X Syndrome (Superfemale)
This syndrome usually results from errors in maternal meiosis I (90% of cases), and its incidence is about 1:1000. Such patients have non-specific features e.g. average intelligence, normal sexual development. About 70% have serious learning problems. In 47,XXX cells, two of the X chromosomes are inactivated. Variations include:
 * tetrasomy X syndrome (48,XXXX) with more serious physical and mental retardation;
 * pentasomy (49,XXXXX) with severe developmental retardation.

XYY Syndrome (Supermale)
It has an incidence of about 1:1000 male live births. It may be caused by paternal non-disjunction at meiosis II (producing a YY sperm) or by a post-zygotic event. Variants of this syndrome include XXYY and XXXYY, which probably also originate from paternal non-disjunction at both meiosis I and II. Patients are usually phenotypically normal and may have the following features:
 * 1) tall stature;
 * 2) severe acne;
 * 3) average intelligence;
 * 4) antisocial behavior with increased risk of behavioral problems (3% are in prisons & mental hospitals);
 * 5) can show emotional immaturity and impulsive behavior;
 * 6) normal fertility, without risk of chromosomal aberrations in offspring;
 * 7) normal sexual development.

Related articles

 * Chromosomal abnormalities