Otopathology in a case of type I Waardenburg's syndrome

We report a case of type I Waardenburg's syndrome that provides insight int o the etiopathogenesis of sensorineural hearing loss (SNHL) in this syndrom e. The subject, a 76-year-old woman with type I Waardenburg's syndrome (dys topia canthorum, heterochromia irides, and white hair), had congenital low- frequency SNHL in her right ear only, which had remained relatively stable throughout her life. Blood leukocyte DNA studies revealed a PAX-3 mutation with a I base pair C-to-A substitution in exon 5 at base 602. Light microsc opic studies of the right cochlea showed intact neurosensory structures in only the lower basal turn, with the remainder of the cochlea showing absenc e of melanocytes, absence of stria vascularis, missing hair cells, dysmorph ogenesis. of the rectorial membrane, and lack of peripheral processes of th e spiral ganglion cells. There was pathological alteration of the vestibula r dark cells with marked reduction of melanocytes associated with these dar k cells. The left inner ear was normal, with a full complement of neurosens ory structures, including melanocytes. Because the PAX-3 gene is involved i n neural crest development and melanocytes migrate from the neural crest to the ear, the findings in this case are consistent with the hypothesis that defective melanocyte migration or defective melanocyte function results in defective development of the stria vascularis (and perhaps other structure s of the ear), leading to SNHL.