Disorders of the Sex Chromosomes

Sex chromosome abnormalities, like autosomal abnormalities, can be either numerical or structural, and can be present in all cells or in mosaic form. Clinical indications that raise the possibility 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 these defects are less severe than autosomal defects and this is due to X chromosome inactivation and the low gene content of Y chromosome, that minimize the clinical consequences of sex chromosome imbalance. X chromosome inactivation is the the process by which most genes on one of the 2 X chromosomes in females are silenced epigenetically and 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. In normal female cells, the choice of which X chromosome is to be inactivated is a random one. Thus females are mosaic with respect to X-linked gene expression. In patients with extra X chromosomes, any X chromosome in excess of one is inactivated, but not all genes on that chromosome are inactivated.

The most common sex chromosome defects are the TRISOMIC TYPES (XXY, XXX, XYY), but these are rare in spontaneous abortions. Structural abnormalities are less common; the most frequent example is an isochromosome of the long arm of X, i(Xq), seen in complete or mosaic form in at least 15% of females with Turner syndrome. Mosaicism is more common for sex chromosome abnormalities than for autosomal abnormalities.