Ruling in and ruling out: implications of molecular genetic diagnoses for disease classification

We report on a qualitative analysis of interviews with 14 genetic counsellors in Ontario, Canada about the implications of developments in molecular genetic knowledge for disease definition and classification. Genetic counsellors express a restrained set of hopes and expectations about the utility of genetic diagnoses. They identify several limitations faced by available genetic tests, limitations that constrain the significance of genetic information in disease identification and clinical management. Yet they also emphasize the fundamental nature of genetic information, its decisive role in specifying disease causation, and its significance for disease classification. The decisive nature of genetic information means that, in some cases, genetic tests foster change in disease categories. Diseases are redefined by the "ruling in" of atypical cases demonstrating a broader spectrum of clinical effects, or the "ruling out" of typical cases with classic clinical presentations that are better assigned to other (or no) causes. These redefinitions can be profoundly consequential, producing several kinds of uncertainty: What do we call this state of being? How do we manage it clinically? And, what are the social entitlements of individuals in this state? Though limited today, such complex effects can be expected to increase, alongside the growing diagnostic power of molecular genetics.