Pendred syndrome (PDS) is a common form of syndromic deafness. At least 5% of the total cases with congenital deafness are PDS. Typical PDS has the association of congenital bilateral neurosensory deafness, thyroid goiter, cochleovestibular malformation and potential vestibular dysfunction. The severity of the symptoms and the age of onset vary from case to case. Deafness often appears at birth, but it may develop in late infancy or early childhood. Sometimes, deafness is asymmetrical or fluctuant and often it is progressive. Abnormal bones of the inner ear can be observed in PDS. Thyroid status varies from euthyroid (goiter) to hypothyrodism. Goiter is secondary to abnormal iodine transport across the thyrocyte and it develops most commonly during adolescence. Incidence differs according to geographic location with a range between 1/100,000 births and 10/100,000 births. Audio-prosthetic management of deafness can be helpful and if the goiter becomes compressive because of excessive size, a thyroidectomy must be performed.
Al Attia et al. (1986) reported an 18-year-old Egyptian male with Pendred Syndrome (PDS). His parents were first cousins and they were residing in the UAE. Around the age of one year, his mother suspected hear defect and a year later, she noticed that he was also dumb. At the age of 15, he developed goiter and being shorter in stature than the relevant group. Hormonal assays, radioactive iodine uptake, and radiological studies of bone age showed results of primary hypothyroidism with bone age of 11-13 years. Bradycardia and slow relaxing ankle jerks was observed in 17 year of age along with goiter. At 18 years, he had moderately sized multinodular goiter and a right hydrocele. His TSH level was elevated. Potassium Perchlorate Discharge test was performed showing a positive perchlorate discharge and indicated an organification defect (T3&T4 forming defect). The patient improved due to daily thyroxine therapy. A radioactive iodine uptake (RAIU) was within normal range because of thyroxine therapy. A month later, the patient displayed a regression of his goiter and his pulse rate became within the normal range.
[Al Attia HM, El-Hag IA, Habab NH, Kazim S. Pendred's Syndrome. Emirates Med J. 1986; 4:140-2.]
Mustapha et al (1998) undertook linkage analysis on a large consanguineous pedigree affected with Pendred Syndrome. A total of 17 members from this family were haplotyped, which included six affected members. The study was able to refine the Pendred syndrome gene to a 0.8 cM interval flanked by markers D7S496 and D7S2425.
Walsh et al. (2006) undertook a study to identify the genes responsible for inherited hearing loss, by linkage scan using microsatellite markers in 156 affected individuals and their families. Walsh et al. (2006) identified two Palestinian families with mutations in the PDS gene; both diagnosed with prelingual, bilateral, severe to profound hearing loss. Four members in the first family were seen to be affected. All of them were found to be homozygous for a missense mutation (c.716T>A; p.V239D), while all unaffected members of the family were found to be either heterozygous carriers of this mutation or wild type. Evaluation of the temporal bones of affected patients showed enlargement of the vestibular aqueducts, confirming Pendred syndrome. The second family too had four affected individuals. However, all of them were homozygous for a splice site mutation (c.1001G>T), while all unaffected members of the family were found to be either heterozygous carriers of this mutation or wild type.
Masmoudi et al. (2000) performed molecular analysis of the PDS gene in two large consanguineous families from southern Tunisia with a total of 23 individuals who had profound congenital deafness; the same missense mutation, p.L445W, was identified in all affected individuals. A widened vestibular aqueduct was found in all patients who underwent CT scan of the inner ear. In contrast, goiter was present in only 11 affected individuals; 8 of these patients who were tested had a normal result on perchlorate discharge test. This finding called into question the sensitivity of the perchlorate test for the diagnosis of Pendred syndrome. Masmoudi et al. (2000) suggested the use of molecular analysis of the PDS gene in the assessment of individuals with severe to profound congenital hearing loss associated with inner ear morphologic anomaly even in the absence of thyroid goiter.
[See: Egypt > Al Attia et al., 1986]
[[Al Attia HM, El-Hag IA, Habab NH, Kazim S. Pendred's Syndrome. Emirates Med J. 1986; 4:140-2.]]