[From degeneration to anticipation. Systematic and historical scientific aspects of the genetics of neuropsychiatric diseases].

Triplet-repeat mutations are a newly discovered class of mutations that have so far been described only in patients with neuropsychiatric disorders. The features of these so-called dynamic mutations are discussed with reference to the known examples (Huntington's chorea, fragile X syndrome, myotonic dystrophy, X-linked spinal and bulbar muscular atrophy, spinocerebellar ataxia type 1, and dentatorubral and pallidoluysian atrophy, DRPLA). These features not only explain a number of clinical-epidemiological facts that cannot be accounted for by Mendelian genetics, but also suggest that schizophrenia and major affective disorder may be the result of a similar mutation mechanism. The most important support for this suggestion can be derived from the observation that dynamic mutations cause anticipation-i.e., an increase in severity and/or an decrease in the age at onset of a disease in subsequent generations-which, in turn, has been discovered in schizophrenia and major affective disorder. From a systematic as well as from a historical perspective, we argue that in light of these findings, degeneration has been rediscovered in the disguise of a new name.