Cascade testing is usually simpler, faster, and less expensive than the first test in the family. The index patient’s test often looked at many genes at once, searching for an unknown change. For a relative, the laboratory already knows exactly what to look for. It checks only that one specific change, at that one position in the DNA. This is called targeted or familial variant testing, and it can usually be done on a blood or saliva sample.

It helps if the relative’s laboratory has a copy of the index patient’s report, which names the gene and the exact change. Without it, the laboratory may need to run a much broader and costlier test.

• A positive result The relative carries the same genetic change. This does not mean they have the condition or will definitely develop it. It means they have the same increased risk as the index patient, and a doctor can advise on screening, prevention, or treatment. For carriers of a recessive condition, it means they are healthy but should consider partner testing before pregnancy.

• A negative result The relative does not carry the family’s genetic change. In most cases, this is a true negative: their risk for that condition returns to the same level as the general population. They usually do not need the extra screening that the rest of the family needs, and their children cannot inherit the change from them. This is often a very meaningful and reassuring result.

• An important limitation A negative targeted test only rules out the specific change already found in the family. It does not rule out other genetic changes. If a relative has a strong personal or family history on the other side of the family, a broader test may still be appropriate.

In a small number of families, the index patient’s result is a “variant of uncertain significance”, meaning the laboratory cannot yet say whether the change causes disease. Cascade testing is generally not recommended for these changes, because a result in a relative would not give a clear answer either.

A genetic counseling session before testing helps each relative understand what a positive or negative result would mean for them before they decide.