Chromosome alterations that are sufficiently large to be observable under a microscope are termed chromosome abnormalities. The study of chromosomes and their abnormalities is termed cytogenetics.

Chromosome abnormalities are responsible for a significant proportion of genetic diseases, occurring in approximately 1 in 150 live births. They are the leading known cause of both mental retardation and pregnancy loss. Chromosome abnormalities are seen in approximately 50% and 20% of first- and second-trimester spontaneous abortions, respectively. Specific chromosome abnormalities are also associated with many cancers.

• What are the indications for chromosome analysis?
  • Prenatal
    • Women 35 years or older at delivery
    • Positive maternal serum screening test
    • Abnormal ultrasound findings
    • History of 2 or more miscarriages or unexplained infertility
    • Previous child with chromosome abnormality
    • Known translocation carrier
  • Postnatal
    • Multiple congenital abnormalities
    • Developmental delay
    • Short stature and or delayed puberty
    • Child with known chromosome abnormality such as Down syndrome
    • Parents and children of persons with translocations, deletions or duplications
    • Suspicion of the fragile-X syndrome
  • Oncology
    • Preneoplastic disorders, such as myelodysplastic syndrome, pancytopenia, or preleukemia
    • Leukemia or lymphoma
    • Solid tumor
    • Bone marrow transplants, pretransplant and follow-up studies
• What is the cost of chromosome analysis?
  
The cost of a chromosome analysis will vary with the type of specimen and the amount of work required to reach a conclusion for an individual patient. Chromosome analysis is a complex laboratory service and sometimes requires multiple days or weeks of specimen handling and processing before an analysis is complete. At this time, almost no aspect of this test is automated. We recommend that you refer to the Directory of Laboratory Services for:

or your physician for more details.

What are some of the major limitations of cytogenetics testing?

There are many factors that can contribute to birth defects. Some of them have a genetic basis, some do not. The incidence of genetic disorders and other congenital anomalies seen by age 25 is about 80 of 1000 live births. Of these 80 individuals, approximately two will have anomalies as a result of a chromosome abnormality. The disorders in the remaining 78 patients will be due to a cause other than a chromosome abnormality. A normal karyotype, therefore, does not rule out some other cause of a genetic problem.

Very often a chromosome analysis is ordered as an initial look at the total amount of genetic material in a child exhibiting abnormal growth and/or development, in order to eliminate a chromosomal basis for that problem. However, if the problem is due to a single or even multiple gene defect, it will not be seen under the microscope for most conditions of this nature.

Chromosome studies focus on extra chromosomes in the cells (trisomy), missing chromosomes (monosomy), and balanced and unbalanced rearrangements of the chromosomes. A good discussion of these aspects of cytogenetic studies can be see in the Chromosome Deletion Outreach Support Group Webpage at: http://www.chromodisorder.org/intro.htm.

There are many newer sophisticated techniques that can look at more detailed level of chromosome structure, however these techniques do not allow visualization at the level of a single gene. The microdeletion syndromes such as Williams syndrome
( Williams Syndrome U.S. Association ), Prader Willis syndrome ( Prader-Willi Foundation ), Angelman syndrome, and DiGeorge/Velocardiofacial syndrome ( 22q and you newsletter ), represent the smallest size of chromosomal abnormality that can be visualized using cytogenetic techniques. The deleted material seen under the microscope contains multiple genes. The choice of probes to be utilized in a microdeletion study is by the patient's clinical presentation.