Test Evaluation

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Genetic Test Considerations

Genetic testing has the potential to be a very powerful tool. However, it also has a great number of technical caveats and limitations. These unique qualities must be well understood to provide patients with best care.

When deciding whether genetic testing is warranted in a specific case, several factors should be considered.

Clinical Availability of Testing

It should be noted that for many genetic disorders, no genetic test is available on a clinical basis. Diagnosis of these conditions relies on physical examination, family history, personal medical history, and other appropriate studies. Possible reasons for a lack of genetic testing for a given disorder include the following:

  • One or more of the genes responsible for the condition have not been identified.
  • Specific mutations in the relevant gene(s) have not been well characterized.
  • The disorder is so uncommon or testing is of such little utility that there is limited interest in developing and offering testing on a clinical basis.
Clinical Utility of Testing

The vast majority of genetic disorders lack a cure. Some disorders do have an effective treatment program; for the most part, however, clinicians are left managing symptoms. When there are no effective treatments, the use of genetic testing to diagnose a condition presymptomatically or to identify an individual as at risk to have an affected child is a complex and personal decision. Some patients may perceive testing as a benefit, even in the absence of treatment options. Benefits might include reduced uncertainty, avoidance of increased surveillance if a test is negative, and the possible avoidance of conception or birth of an affected child. These potential benefits must be weighed against such concerns as psychological harm and potential for discrimination (insurance, employment, and other forms). The genetic testing decision in these situations, therefore, is often based on a combination of personal values and motivations as well as medical management.

Clinical Validity of Tests

Genetic test results can be challenging to interpret and require an understanding of the sensitivity, specificity, and positive predictive values of different methodologies. "Positive" test results do not necessarily mean that a person will develop symptoms of the condition tested for, and "negative" results may not rule out the possibility that the person is affected or at risk for developing a condition.

Listed below are the major factors impacting the clinical validity of a genetic test. The validity issues associated with molecular genetic testing are most pronounced and will be explored further in subsequent pages. However, it should be noted that each of these factors can also impact cytogenetic and gene-product testing. Regardless of the type of genetic testing ordered, the following factors should be considered when investigating all types of genetic testing:

  • Sensitivity of the methodology
  • Family member cooperation
  • Penetrance of the disorder
  • Variable expressivity
  • Result interpretation for variants

These factors will be explored further in the coming pages.