Anticipation with phenotypic variation in three father-son pairs with affective disorder: a case series.

Anticipation is a phenomenon in which successive generations within a family experience an earlier age of onset and a more severe form of a given illness. It has been observed in various neurological and psychiatric conditions, including bipolar disorder. The molecular basis of anticipation involves trinucleotide repeat expansions in genes, but this has not been conclusively demonstrated in bipolar disorder. The histories of 3 father-son pairs are presented. In each pair, the son presented with an early-onset bipolar disorder, and the father developed severe depression after the age of 50 years. No female relatives were affected. The implications of these observations are discussed. Genetic, epigenetic, and environmental mechanisms that may have contributed to this phenomenon are briefly described. The study of such patients may throw light on the "extended phenotype" of mood disorders, as well as the genetic and epigenetic mechanisms involved in the phenomena of anticipation and phenotypic variation.