Pendred's syndrome is a combination of congenital sensorineural hearing loss and 
iodine organification defect leading to a positive perchlorate test and goiter. 
Although it is the commonest form of syndromic hearing loss, the variable 
clinical presentation contributes to the difficulty in securing a diagnosis. The 
identification of the disease gene (PDS) prompts the need to reevaluate the 
syndrome to identify possible clues for the diagnosis. To this purpose, in three 
Italian families presenting with the clinical features of Pendred's syndrome, 
the molecular analysis was accompanied by full clinical, biochemical, and 
radiological examination. A correlation between genotype and phenotype was found 
in the only patient with enlargement of vestibular aqueduct and endolymphatic 
duct and sac at magnetic resonance imaging. This subject was a compound 
heterozygote for a deletion in PDS exon 10 (1197delT, FS400) and a novel 
insertion in exon 19 (2182-2183insG, Y728X). The present study demonstrates for 
the first time the value of the combination of clinical/radiological and genetic 
studies in the diagnosis of Pendred's syndrome. The positivity of a perchlorate 
discharge test and the malformations of membranous labyrinth fit well with the 
recent achievements on the role of pendrin in thyroid hormonogenesis and the 
maintenance of endolymph homeostasis.