The main principles of clinical genetics are pleiotropism, genetic heterogeneity, and variation. Pleiotropism—multiple phenotypic effects of a single mutant gene, the basis of syndromes—mandates lumping of disorders that may have been separately described on the basis of features that predominate in one group of patients. Genetic heterogeneity, however recognized, is a basis for splitting. Some aspects of variation will be discussed later, in connection with multifactorial inheritance.