Waardenburg syndrome is a recognizable disorder characterized by autosomal dominant inheritance of pigmentary abnormalities of the eyes, hair, and skin sometimes associated with congenital hearing impairment. At least two different types of Waardenburg syndrome have been described. The different types of Waardenburg syndrome are differentiated as follows: type I, with dystopia canthorum; type II, without dystopia canthorum; and type III, without dystopia, with unilateral eyelid ptosis and skeletal abnormalities. Results of pooled linkage analysis done by a consortium of investigators suggests that Waardenburg syndrome type I is genetically heterogeneous, meaning that there is probably more than one genotype that can be associated with the findings typical of the syndrome. A mutated gene that can cause Waardenburg syndrome type I has been discovered. Either a single base pair substitution or an 18 base pair deletion in exon 2 has been found in affected individuals but is not found in unaffected members. Most likely, the mutated gene causes a perturbation in DNA binding of a paired domain, in turn having an effect on the regulation of other genes so the development and spatial orientation of cells and structures derived from the neural crest are affected. Forty years after Waardenburg syndrome was first described, a mutant gene has been found that is known to cause the syndrome. The process of discovery that has transpired in the time from syndrome description to gene identification has been one of steady progress and interdisciplinary cooperation.(ABSTRACT TRUNCATED AT 250 WORDS)