In our previous post, “Unavoidable vs optional incidental findings: What you need to know”, we discussed the difference between related and unrelated (incidental) findings. As well as the difference between unavoidable and optional incidental findings – and specifically optional incidental findings in the set of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG).
- Findings in the set of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG)
- Findings in other genes
In this post we’ll explore examples of these other genes that are not part of the ACMG’s recommended set, but are similar in that they have some associated actionability and could likewise impact medical management and decision making.
Increased cancer screening
A number of cancer-related genes are part of the ACMG 59 set, but there are additional genes with strong cancer associations. Like RECQL which is associated with increased risk of breast and thyroid cancers.
Possible cardiac implications
The ACMG 59 set is also heavily focused on genes related to cardiac conditions, but there are additional genes associated with cardiac diseases (such as those predisposing to sudden cardiac death) for which possible treatment is available. Like TTN which, like a number of ACMG 59 genes, is associated with dilated cardiomyopathy.
Monitoring of clotting effectiveness before and after surgery
A partial deficiency in one of the clotting pathway enzymes can affect the ability of blood to clot, or can cause it to clot excessively. Examples include the following:
F2 – individuals with a pathogenic variant in F2 are at an increased risk of forming abnormal blood clots as well as an increased risk of developing a pulmonary embolism.
F11 – individuals with a pathogenic variant in F11 exhibit reduced clotting and have difficulty stopping the flow of blood from a deep wound or surgical incision.
Monitoring iron levels
Hereditary hemochromatosis, caused by pathogenic variants in the HFE gene, can result in too much absorption of iron that is consequently stored within the body’s organs including the heart, liver and pancreas. Many individuals with hereditary hemochromatosis do not exhibit signs or symptoms until later in life, if at all. But once aware of the risk, can readily be monitored for high iron levels.
Agents or foods to avoid
There are a number of enzymatic deficiencies that typically present with no or mild symptoms, but which can become serious when a triggering food or agent is present. Examples include the following:
DPYD – individuals with dihydropyrimidine dehydrogenase (DPD) deficiency caused by pathogenic variants in DPYD are at an increased risk of 5-fluorouracil (5-FU) toxicity, a chemotherapy agent that should be avoided.
G6PD – pathogenic variants in G6PD are associated with glucose-6-phosphate dehydrogenase deficiency which can result in hemolytic anemia. Most individuals with G6PD deficiency do not experience symptoms, but symptoms can be brought on by certain triggers. Being aware of and addressing unavoidable triggers like bacterial and viral infections and avoiding others like triggering medications and dietary items can reduce or avoid the onset of symptoms.