Although the textbook view of Pendred syndrome is that of an autosomal recessive 
condition characterized by deafness and goitre, it is increasingly clear that 
not all such patients present this classical clinical picture. Malformations of 
the inner ear, specifically enlargement of the vestibular aqueduct, are common 
in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been 
recorded in patients presenting with deafness and vestibular aqueduct dilatation 
only, without other features of Pendred syndrome. Since this is the most common 
radiological malformation of the cochlea in deaf patients, we investigated what 
proportion of such cases were due to mutation of the PDS gene. We assessed 57 
patients referred with radiological evidence of vestibular aqueduct enlargement, 
by history, clinical examination, perchlorate discharge test and molecular 
analysis of the PDS locus. Forty-one patients (72%) had unequivocal evidence of 
Pendred syndrome. The finding of a single heterozygous mutation at the PDS gene 
in a further eight was strongly suggestive of a critical role for pendrin, the 
protein product of the PDS gene, in the generation of enlarged vestibular 
aqueducts in at least 86% (49/57 cases) of patients with this radiological 
malformation. Securing the diagnosis of Pendred syndrome may be difficult, 
especially in the single case. Goitre is an inconstant finding, and the 
perchlorate discharge test, although helpful, is of diagnostic value only if 
abnormal. Enlargement of the vestibular aqueduct should be considered as the 
most likely presentation of Pendred syndrome and should prompt specific 
investigation of that diagnostic possibility. Pendred syndrome might henceforth 
be recharacterized as deafness with enlargement of the vestibular aqueduct, 
which is sometimes associated with goitre.