What are reduced penetrance and variable expressivity?
Reduced penetrance and variable expressivity are factors that influence how genetic variants manifest as signs and symptoms in an individual.
Reduced Penetrance
Penetrance refers to the proportion of people with a particular genetic variant who exhibit signs and symptoms of a disorder. If some people with the variant do not develop any features of the condition, it is called reduced (or incomplete) penetrance.
This is often seen in familial cancer syndromes. For example, many people with a variant in the BRCA1 or BRCA2 gene will develop cancer, but some will not. Because the cause—a combination of genetic, environmental, and lifestyle factors—is often unknown, it can be challenging for professionals to predict who will develop the condition.
Variable Expressivity
Variable expressivity refers to the range of signs and symptoms that can occur in different people with the same genetic condition. While some disorders show little variation, most exhibit a spectrum of severity.
For example, in Marfan syndrome, individuals with a variant in the FBN1 gene may experience vastly different symptoms. Some may only have mild features, such as being tall and thin with long fingers, while others may face life-threatening complications involving the heart and blood vessels. Like reduced penetrance, this variation is likely caused by a combination of unidentified genetic, environmental, and lifestyle factors, which can make diagnosis difficult.