Changes in clinical practice with the unravelling of diseases: Connective-tissue disorders

Unravelling of diseases is achieved in steps by sequentially describing the ir phenotype, natural course, aetiology and pathogenesis. Through succinct clinical observation, conglomerates of heterogeneous connective-tissue diso rders, such as various forms of disproportionate dwarfism, have been split into well-defined entities. They have often been confirmed by biochemical a nd molecular analysis. On the other hand, seemingly disparate disorders hav e been shown to be pathogenetically related and to be variable expressions of common defects. Examples are the mucopolysaccharidoses and type II colla genopathies. Disease recognition through splitting and lumping has improved prevention and prognostication. It is the basic requirement for future the rapeutic attempts on a pathogenetic or molecular level.