Heterochrony and human malformation.

Abstract

The role of altered developmental timing or heterochrony in morphologic evolution has intrigued classical and modern biologists. Analogous manifestations of developmental asynchrony occur in human dysmorphogenesis where they illustrate the residue and repertoire of phylogenetic change. Certain single malformations such as holoprosencephaly immediately suggest heterochrony by their resemblance to antecedent phylogenetic or embryologic structures. Multiple malformation syndromes of genetic, chromosomal, or teratogenic etiology may have altered developmental timing as an underlying theme. The persisting alpha-fetoprotein synthesis in ataxia-telangiectasia, the morphologic atavisms in Down or trisomy 13 syndromes, and the delayed growth or fetal to adult hemoglobin switch in diabetic embryopathy all exemplify developmental asynchrony. The perspective of heterochrony stresses the molecular history and hierarchy which is recapitulated with each pregnancy, and reconciles apparent discrepancies between the rates of molecular and morphologic evolution. Recognition of heterochrony places isolated anomalies in the context of pattern and suggests monitoring of teratogenesis through altered expression of ontogenetically regulated, phylogenetically relevant molecules.