Pendred syndrome and the enlarged vestibular aqueduct (EVA) are considered 
phenotypic variations of the same entity due to mutations in the SLC26A4 
(pendrin) gene. Pendred syndrome consists in sensorineural deafness, goiter and 
impaired thyroid hormone synthesis while in EVA thyroid function seems to be 
preserved. The aim of this study was to evaluate thyroid function and morphology 
and to look for mutations in the SLC26A4 gene in patients presented with EVA. 
Among 57 consecutive patients with sensorineural deafness 15 with EVA, as 
assessed by magnetic resonance imaging (MRI), were identified and studied. A 
complete evaluation of thyroid function including thyroid echography and 
perchlorate discharge test was carried out in all patients with EVA; all exons 
of the SLC26A4 gene were amplified from peripheral leukocytes and directly 
sequenced, using specific intronic primers. Out of 15 patients with EVA, goiter 
was present in 8 (53%), hypothyroidism in 7 (47%), increased serum thyroglobulin 
levels in 8 (53%) and a positive perchlorate discharge test in 10 (67%). Nine 
alleles of the SLC26A4 gene were mutated: 2 novel mutations (L465W and G497R) 
and 4 already known mutations (T410M, R409H, T505N and IVS1001+1G>A) were found. 
Four subjects were compound heterozygous and 1 heterozygous (G497R/wt). All 
patients harbouring mutations in the SLC26A4 gene had goiter and a positive 
perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid. The 
remaining 10 patients had no mutations in the SLC26A4 gene: 4 of them were 
hypothyroid, 2 with goiter and positive perchlorate discharge test, 2 without 
goiter and with negative perchlorate discharge test. Two patients without 
mutations were euthyroid with positive perchlorate discharge test. Patients with 
mutations in the SLC26A4 gene had larger thyroid volume (p<0.002), higher serum 
thyroglobulin (Tg) levels (p<0.002) and greater radioiodine discharge after 
perchlorate (p=0.09) than patients without mutations. The results of the present 
study lend support to the concept that all patients with mutated SLC26A4 gene 
have abnormalities of thyroid function tests.