Chromosomal abnormalities occur in approximately 1 of 200 term pregnancies and in 1%–2% of all pregnancies involving parents older than 35 years. About 7% of perinatal deaths and some 40%–50% of retrievable spontaneous abortuses have significant chromosomal aberrations. Virtually any change in chromosome number during early development profoundly affects the formation of tissues and organs and the viability of the entire organism. Most major chromosomal disorders are characterized by both developmental delay and cognitive disability, as well as a variety of somatic abnormalities.
Indications for and Types of Chromosome Analysis
Ophthalmologists should be aware of the value of learning the constitutional and tumor karyotypes for infants with retinoblastoma, especially if the tumor represents a new genetic mutation. Chromosome analysis (also called karyotyping) is also suggested in patients with isolated (nonfamilial) aniridia (which is often associated with Wilms tumor) and other systemic malformations.
A chromosomally abnormal state in a previous child warrants consideration of amniocentesis or chorionic villus sampling for prenatal diagnosis in subsequent pregnancies to avoid the risk of recurrence. An alternative is the use of preimplantation genetic diagnosis (discussed later in the chapter, under Reproductive Issues).
The systematic display of chromosomes from a single somatic cell is called a karyotype. Chromosome preparations are most commonly obtained from peripheral venous blood, although bone marrow, skin fibroblasts, and cells from amniotic fluid or chorionic villi are useful under specific circumstances. Chromosome analysis can be obtained directly from neoplastic tissues, as in retinoblastoma and Wilms tumor, for example.
Fluorescence in situ hybridization and chromosome arm painting
With the fluorescence in situ hybridization (FISH) technique, DNA fragments from genes of interest are first tagged with a fluorescent compound and then annealed or hybridized to chromosomes. In the process of chromosome arm painting, the regions of interest are stained to determine whether duplication, deletion, or rearrangement has occurred. Such fluorescent molecular probes can be used to detect and often quantify the presence of specific DNA sequences on a chromosome and can identify microscopic abnormalities that would be indiscernible by conventional cytogenetic methods.
Figure 6-6 Composite karyotype of all human chromosomes hybridized with chromosome arm painting. Metaphase chromosomes were hybridized simultaneously with corresponding short-arm (red) and long-arm (green) painting probes, and a composite karyotype was generated.
(Reproduced with permission from Guan XY, Zhang H, Bittner M, Jiang Y, Meltzer P, Trent J. Chromosome arm painting probes. Nat Genet. 1996;12(1):10–11.)
Using microdissections of chromosomal regions and FISH, probes have been developed that label entire arms of chromosomes and each of the individual chromosomes (multicolor spectral karyotyping and combinatorial multifluor FISH). With 2-color FISH, both arms of each chromosome can be labeled simultaneously (Fig 6-6). These probes are valuable for detecting and understanding the mechanisms of complex chromosomal rearrangement.
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.