Enlarged vestibular aqueduct (EVA) is the most common malformation of inner ear associated with sensorineural hearing loss. It can either be found in nonsyndromic or in syndromic forms of hearing loss, such as Pendred syndrome (PS). In PS, sensorineural deafness is associated with thyroid abnormalities: goitre and iodine organification defect detected with perchlorate discharge test. Mutations in SLC26A4 (PDS) gene cause PS and can also be found in a proportion of patients presenting with nonsyndromic hearing loss with EVA. It is not clear yet whether PS and nonsyndromic EVA represent two distinct clinical and genetic entities or whether they are part of a continuum of the same disorder. Mutations of SLC26A4 were screened by denaturing high-performance liquid chromatography (DHPLC) in 15 PS patients and in 21 nonsyndromic EVA patients. Thyroid function evaluation was performed, including morphological evaluation of thyroid gland, a perchlorate discharge test and thyroid function tests. In all 15 PS patients, two SLC26A4 mutated alleles were found. One or two SLC26A4 mutated alleles were found in 10 out of the 21 nonsyndromic EVA patients (48%). One mutant allele was detected in 7 patients and 2 mutant alleles were detected in 3 patients. No mutation was found in the other 11 patients. All nonsyndromic EVA patients revealed normal thyroid evaluation, excepted for 2 patients carrying 2 mutant alleles who showed isolated elevated serum thyroglobulin values. Five novel mutations were described. The results of this study support the fact that SLC26A4 mutations are frequent in nonsyndromic EVA Caucasian patients and that most of them have only one mutated allele, suggesting the involvement of other genetic or environmental cofactors. We also hypothesise that nonsyndromic EVA patients carrying two SLC26A4 mutant alleles may present a subtle iodine organification defect, revealed by elevated serum thyroglobulin value.
01 - 05 Apr 2006
European Society of Endocrinology