Identifying patients for whom genetic or genomic testing is appropriate begins with a clinical evaluation and a good understanding of the phenotype. Knowledge of ethnicity and family history is important, so taking a three-generation history is vital. However, an absence of any relevant family history does not rule out a genetic condition.
Genomic testing can be a time- and/or cost-effective diagnostic approach for patients suspected of having a monogenic (Mendelian) condition – as opposed to a polygenic or multifactorial condition. A monogenic condition is caused by a pathogenic variant in only one gene. However, there could be more than one candidate gene responsible; this is known as genetic heterogeneity. For example, one disease might have over 50 different monogenic causes (high genetic heterogeneity) or only five different monogenic causes (low genetic heterogeneity).
The clinical utility of genomic testing varies across different disorders. In most cases, results will not alter prognosis, management or treatment. But results can bring a long, expensive diagnostic odyssey to an end. The information may also be useful for reproductive planning and/or other family members.
Genomic testing is not indicated in patients:
- where there is a low chance they have a monogenic condition
- where there is a known pathogenic variant in the family (targeted testing might be more appropriate)
- for whom you suspect the cause of their condition is a genetic variant type that is best identified by an alternative test type (e.g., a triplet repeat, a chromosome deletion or aneuploidy).