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INTRODUCTION

A common misconception in the medical community is that genetic disorders consist of a collection of extremely rare conditions that are seldom relevant to day-to-day clinical practice. In fact, essentially every medical condition affecting humankind has at least some genetic component to its etiology. The study of how mutations in single genes cause rare disease (genetics) is gradually being eclipsed by research on how mutations in multiple genes interact with each other and the environment to result in health and disease (genomics). Knowledge derived from genomic discoveries is reshaping the underpinnings of much of medical practice, and will continue to do so for decades to come. At a practical level, recent advances have taught us a tremendous amount about the basis of common conditions such as diabetes, heart disease, and cancer. This new knowledge is being rapidly translated into approaches for disease risk assessment, prevention, and treatment. Likewise, the study of how genes affect drug metabolism (pharmacogenetics) is being increasingly used to inform drug prescribing (see Chapter 49). Importantly, primary care physicians should not lose sight of the fact that so-called rare single-gene disorders collectively represent a significant proportion of pediatric and adult illnesses.

Primary care physicians are in a unique position to diagnose genetic disorders because they are often the first contact for patients and also provide care for multiple family members. Recognition of, and subsequent attention to, the presence of genetic risk factors for disease in an individual can be lifesaving for individuals and their relatives. Further, as pharmacogenetics becomes increasingly important to drug therapy, primary care providers will need to be aware of and comfortable with ordering and interpreting this type of testing prior to prescribing a variety of medications.

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Feero  W  et al.. Genomic medicine—an updated primer. N Engl J Med. 2010; 362:2001–2011.
[PubMed: 18349096]

GENETIC EVALUATION

Family History

Most common diseases result from a combination of exposure to environmental factors and the effects of variations in multiple genes. Inherited variations confer individual risks that can be distinguishable from the population-based average, and hundreds of such variations have been discovered over the last several years for conditions ranging from schizophrenia to Parkinson disease to coronary artery disease. However, for most conditions the genetic variations discovered to date explain only a small fraction of the heritable component of disease risk in any given individual—for example, in type 2 diabetes well over a dozen genetic variations have been discovered, yet collectively they explain only 5–10% of heritable disease risk.

Obtaining a medical family history provides the most effective current method to rapidly determine whether an individual is at genetic risk of developing common disorders. Additionally, for most individuals family history captures at least some of the environmental and cultural contributors to disease risk. For many common diseases, patient-reported family history of disease in first-degree relatives is highly ...

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