Occasionally, an individual or a tissue contains two or more cell lines with distinctly different chromosomal constitutions. Such individuals or tissues are termed mosaics. Sometimes the peripheral blood, which is the usual source for chromosomal analysis, contains populations of cells with completely different chromosomal constitutions. One population of cells may be so infrequent that a second tissue, such as skin fibroblasts, must be analyzed to demonstrate the mosaicism.
The clinical effects of mosaicism are difficult to predict because the distribution of abnormal cells in the embryo is determined by the timing of the error and other variables. If mitotic nondisjunction immediately follows conception, the zygote divides into 2 abnormal cells: 1 trisomic and 1 monosomic. The monosomic cells rarely survive and may decrease in number or even disappear entirely over time. Mitotic nondisjunction may occur when the embryo is composed of a small population of cells. Thus, 3 populations of cells are established—1 normal and 2 abnormal—although some abnormal cell lines may be “discarded” or lost during development. If mitotic nondisjunction occurs at a more advanced stage of development, resulting abnormal populations constitute a minority of the embryo’s cells, and mosaicism may have little or no measurable effect on development.
A small population of aneuploid mosaic cells may not have a direct effect on development. However, when cells of this type occur in the reproductive tissues of otherwise unaffected people, some of the gametes may carry extra chromosomes or may be missing some entirely. Consequently, mosaic parents tend to be at high risk for having chromosomally abnormal children.
The most common example of autosomal mosaicism is trisomy 21 mosaicism. Some patients with trisomy 21 mosaicism have the typical features of Down syndrome; others show no abnormalities in appearance or intelligence. The crucial variables seem to be the frequency and the embryologic distribution of the trisomic cells during early development, which do not necessarily correlate with the percentage of trisomic cells in any one tissue, such as peripheral blood.
Several types of sex chromosome mosaicism may occur. Again, the physical effects tend to vary, probably reflecting the quantity and distribution of the abnormal cells during development. For example, the cell population that lacks 1 of the X chromosomes can arise in a female embryo, leading to 45,X/46,XX mosaicism. In some cases, these patients develop normally; in other cases, some or all of the features of Turner syndrome appear. Similarly, the Y chromosome may be lost in some cells of a developing male embryo. This produces 45,X/46,XY mosaicism. Persons with X/XY mosaicism may develop as phenotypically unaffected males, as females with the features of Turner syndrome, or as individuals with physical characteristics intermediate between the sexes (intersexes or pseudohermaphrodites).
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.