John M. Opitz

It is here argued that the application of the term “minor anomalies” is often imprecise and likely outdated. In the past, the designation was used indiscriminately to refer to a great variety of unrelated morphogenetic phenomena. Also, the term does not discriminate between mild qualitative defects of development (mild malformations) and quantitative variants of normal structure. The human face was formed by natural and sexual selection. Morphological and morphogenetic analyses have shown that the human face with its skin, muscles, nerves, arteries, veins, glands, and lymphatics is a complex structure made up of progeny of ectoderm and mesoderm. Holoprosencephaly demonstrates graphically how these embryonic derivatives fit together sequentially. These derivatives are the adaptive units of the human organism, the result of stringent evolutionary forces uniting essential function to a minimum of structure. Before an “unusual” facial appearance is diagnosed as “abnormal”, phenotype analysis is required to determine if there is a family resemblance or if it is a pleiotropic structure. The facial structures of chimps and humans are homologous by virtue of descent from a common ancestor (Darwin, 1859). Differences in the appearance of these species reflect adaptive divergence over some 6–7 million years of evolution while retaining over 98–99% genetic identity. Both species may develop Down syndrome, evidence of similarly retained developmental plasticity. It has occurred to us that Dobzhansky's axiom (“Nothing in biology makes sense except in the light of evolution”) applies not only to genetics, but to all of medicine.