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Molecular Analysis of the Pendred’s Syndrome Gene and Magnetic Resonance Imaging Studies of the Inner Ear Are Essential for the Diagnosis of True Pendred’s Syndrome¹

Institute of Endocrine Sciences, University of Milan (L.F., D.M., L.P., P.B.P.), Istituto Clinico Humanitas (L.F., D.M., P.B.), Istituto Auxologico Italiano IRCCS (L.P.) and Ospedale Maggiore IRCCS (P.B.P.), 20122 Milan; Departments of Internal Medicine (N.C.), Pediatric Sciences (M.M.), and Otorhinolaryngology (F.P.), Policlinico S. Matteo IRCCS, University of Pavia, 27100 Pavia; and Third Pediatric Clinic, HS Raffaele (G.W.), 20142 Milan, Italy

Address all correspondence and requests for reprints to: Paolo Beck-Peccoz, M.D., Institute of Endocrine Sciences (Pad. Granelli), Ospedale Maggiore IRCCS, Via F. Sforza 35, 20122 Milan, Italy. E-mail: paolo.beckpeccoz{at}galactica.it

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.

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