Introduction
This topic covers genetic heterogeneity: the situation in which one clinically defined disease can be caused by different genes or different mutations, and the related phenomenon of clinical-genetic polymorphism, in which the same genetic defect produces variable clinical expression. Understanding both explains why a single diagnostic label may hide several genetic causes, why recurrence risk depends on the specific gene, and why genetic testing is needed to make a precise diagnosis.
Essence of heterogeneity
A heterogeneous disease is a disorder with a similar or identical clinical picture that results from mutations in different genes (locus heterogeneity) or from different mutations within one gene (allelic heterogeneity). Heterogeneity is common among monogenic diseases and is one reason why many rare Mendelian disorders are difficult to classify clinically. A separate concept, the phenocopy, is a condition that looks like a hereditary disease but is caused by an environmental factor, such as an intrauterine infection or a toxic exposure, and has no genetic basis.