Of all of the literature relating to a specific clinical area in human cytogenetics, the most voluminous is probably that which deals with abnormalities of the X chromosome, particularly monosomy X (45,X or 45,XO) and X-chromosomal deletions. In line with the general thrust of the discussion of aneuploidy in this volume, this chapter will be principally concerned with one aspect of the problem: the influence which the regulation of X-chromosome expression has on the phenotype of X-chromosomal aneuploidy. By virtue of the existence of mechanisms for X-inactivation in human females, interpretation of the effects of X-chromosomal aneuploidy involves considerations which go beyond those applicable to autosomal aneuploidy. These considerations and their application to an understanding of the phenotypes associated with monosomy X and del(X) will be discussed here. Except for the infertility associated with 47,XXY, the other common sex chromosome abnormalities (47,XXY, 47,XXX, and 47,XYY) will not be considered since no specific information beyond that available from analysis of 45,X is available. For a comprehensive review of the cytogenetics of the X chromosome, the reader is referred to the two volumes edited by Sandberg (1983a, b).

Properties of the human X chromosome

The life cycle of the X chromosome

Virtually all work relevant to our understanding of the cycle of X-chromosome inactivation and reactivation during ontogeny has been carried out in the mouse, and most of the data to be presented here are based on experimental work with that species.