Pendreds syndrome with three mutations
P Goulden1, G Bano1, VK Ajith Kumar2, SV Hodgson2 & SS Nussey1
This 48-year-old with consanguineous parentage presented at the age of 23 in 1980 with congenital bilateral sensorineural deafness and hypothyroidism requiring replacement with 150 mcg thyroxine. There was a family history of deafness and thyroid disease. A perchlorate discharge test was performed and 42% of the radioiodine within the gland was discharged by potassium perchlorate (NR <10%).
Over the following decade she developed a diffuse goitre which required treatment with subtotal thyroidectomy because of compressive effects. A CT scan of the petrous temporal bone showed dilated vestibular aqueducts bilaterally.
This case provides a classic example of Pendred syndrome; the most common form of syndromic deafness which is characterized by congenital sensorineural hearing loss and goitre. The gene (SLC26A4) has been mapped to chromosome 7q and encodes a transmembrane protein called pendrin which functions as an iodide transporter. Mutation of this gene decreases organification of thyroglobulin.
Pendred syndrome is diagnosed on the basis of the association of sensorineural hearing loss, goitre and an abnormal perchlorate discharge test. The hearing loss is variable and goitre may not manifest until the second decade. Abnormalities of the inner ear such as dilatation of the vestibular aqueduct and Mondini malformation are seen from early infancy in a very high proportion of patients with this condition. A CT scan of the petrous temporal bone is a useful diagnostic aid. Genetic analysis, on the other hand, is difficult and time consuming often requiring a staged approach. At times, changes of uncertain significance may be identified. Three missense mutations were identified in the SLC26A4 gene in our patient. We are in the process of testing the other affected and unaffected members of the family to identify the pathogenic mutations in this kindred.