Because of the complexity and cost of chromosome analysis, its use is ordinarily limited to cases with specific indications. Apart from the specific phenotypes, in which chromosome analysis is a standard part of clinical evaluation, there are also some nonspecific general clinical indications that suggest a need for cytogenetic analysis:

1. A number of problems of early growth and development. Failure to thrive, developmental delay, dysmorphic facies, multiple malformations, short stature, ambiguous genitalia, and mental retardation are frequent findings in children with chromosome abnormalities, although not restricted to that group. Unless there is a definite nonchromosomal diagnosis, chromosome analysis should be performed for patients presenting with a combination of such problems.

2. Stillbirth and neonatal death. As noted earlier, the incidence of chromosome abnormalities is much higher among stillbirths than among live births. It is also elevated among infants who die in the neonatal period. Chromosome analysis should be performed for all stillbirths and neonatal deaths that might have a cytogenetic basis in order to identify a possible specific cause or, alternatively, to rule out chromosome abnormality as the reason for the loss. In such cases, karyotyping is essential for accurate genetic counseling and may provide important information for prenatal diagnosis in future pregnancies.

3. Fertility problems. Chromosome studies are indicated for women presenting with amenorrhea and for couples with a history of infertility or habitual abortion. A chromosome abnormality (usually a structural rearrangement or sex chromosome mosaicism) is seen in one or the other parent in a significant proportion (3 to 6 percent) of cases in which there have been two successive miscarriages or infertility.

4. Family history. A known or suspected chromosome abnormality in a first-degree relative is an indication for chromosome analysis under some circumstances. Chromosome analysis in phenotypically normal family members is obviously unnecessary when the proband is known to have Down syndrome with trisomy 21. On the other hand, if a patient has translocation Down syndrome, the parents’ chromosomes should be analyzed; it one Parent is found to be a translocation carrier; the study should then be extended to other family members.