What is the difference between penetrance and expressivity, and how do they affect the clinical presentation of an autosomal dominant disorder?

• A. Penetrance is the proportion of individuals with a pathogenic variant who show the phenotype; expressivity is the range and severity of features among those affected.
• B. Penetrance measures the severity of disease; expressivity is the age of onset.
• C. Penetrance is the number of genes involved; expressivity is the number of symptoms.
• D. Penetrance and expressivity are the same.

Answer: (A)

Penetrance is the proportion of individuals who carry a pathogenic variant and actually show the disease phenotype. It can be complete, where every carrier is affected, or incomplete, where some carriers remain asymptomatic. Expressivity describes how the disease presents among those who are affected—the range and severity of features, which can vary from mild to severe and may involve different organ systems. In an autosomal dominant disorder, one mutated allele can cause disease, but whether it does depends on penetrance; among those who are affected, the clinical picture can differ because of expressivity. For example, some individuals may have subtle signs while others have more severe or multisystem involvement. The other statements miss the mark because penetrance is not about severity, age of onset, or the number of genes, and the two terms are not the same.