Although an impaired longitudinal growth is a part of many chromosomal aberrations and a variety of single gene mutations, rarely is it the only symptom of patients with genetic syndromes. Otherwise, in a healthy child, the influence of parental height on the adult height of their children is well established. Although this genetic influence can be easily demonstrated by statistics and is observed over generations, the hormonal and metabolic factors that control the quantitative marker ‘growth’ remain difficult to establish. Genetics has used different approaches to address this question. Linkage studies so far have yielded some new, but partially conflicting, data about the key factors that influence growth and finally adult height. In contrast, the examination of ‘candidate genes’ has been very fruitful in identifying those genes that are responsible for some well-defined hormonal deficiencies in patients with severe short stature.
As the systematic examination of such genes in short children with and without hormonal deficiencies has become feasible, it appears that the phenotypic appearance of some of these disorders is variable to an extent that makes it difficult to differentiate them from a ‘short normal child’. Both the ‘candidate gene’ and the ‘reverse genetics’ approaches using linkage analysis on a whole genome scale have produced results that have already furthered our understanding of the complex mechanisms that influence growth. Both the approaches have come closer to each other, but so far they have not produced the overlap of evidence that one had initially anticipated.