Enlarged vestibular aqueduct: a radiological marker of Pendred syndrome, and mutation of the PDS gene

Although the textbook view of Pendred syndrome is that of an autosomal rece ssive condition characterized by deafness and goitre, it is increasingly cl ear that not all such patients present this classical clinical picture. Mal formations of the inner ear, specifically enlargement of the vestibular aqu educt, are common in Pendred syndrome and mutations in the PDS (Pendred Syn drome) gene have been recorded in patients presenting with deafness and ves tibular aqueduct dilatation only, without other features of Pendred syndrom e. Since this is the most common radiological malformation of the cochlea i n deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene. We assessed 57 patients referred with radiologica l evidence of vestibular aqueduct enlargement, by history, clinical examina tion, perchlorate discharge test and molecular analysis of the PDS locus. F orty-one patients (72%) had unequivocal evidence of Pendred syndrome. The f inding of a single heterozygous mutation at the PDS gene in a further eight was strongly suggestive of a critical role for pendrin, the protein produc t of the PDS gene, in the generation of enlarged vestibular aqueducts in at least 86% (49/57 cases) of patients with this radiological malformation. S ecuring the diagnosis of Pendred syndrome may be difficult, especially in t he single case. Goitre is an inconstant finding, and the perchlorate discha rge test, although helpful, is of diagnostic value only if abnormal. Enlarg ement of the vestibular aqueduct should be considered as the most likely pr esentation of Pendred syndrome and should prompt specific investigation of that diagnostic possibility. Pendred syndrome might henceforth be recharact erized as deafness with enlargement of the vestibular aqueduct, which is so metimes associated with goitre.