Pendred syndrome (PDS; OMIM #274600) is an autosomal recessive disorder characterized by bilateral sensorineural hearing loss with inner ear malformations and goiter, although the thyroid symptoms are variable [Reardon et al., 1999]. PDS is estimated to account for 5% of childhood deafness, rising to 7% in adults since it is usually diagnosed only after the onset of goiter [Fraser, 1976]. The hearing loss is typically bilateral, severe to profound, and prelingual [Fraser, 1976]. However, in some cases, patients show progressive and/or postlingual hearing impairment [Reardon et al., 1997]. In about 50% of the probands from multiplex families, mutations in the SLC26A4 gene, encoding pendrin, are the cause of the disease [Everett et al., 1997]. SLC26A4 is also involved in DFNB4 (MIM #600791), that is, nonsyndromic recessive deafness associated with enlarged vestibular aqueduct (EVA) [Li et al., 1998].
Here we report on the finding of a novel splice-site mutation in SLC26A4, which is associated with Pendred syndrome in two Portuguese siblings (patients 1 and 2).
Patient 1, a 19-year-old male, is the first child of consanguineous healthy parents (Fig. 1a). Pregnancy and delivery were uneventful. The ponderal index was normal, in the 50th centile. At age 2 years, a delay in speech and language acquisition led to an ENT examination, which detected mixed hearing loss in a context of chronic bilateral seromucous otitis. The patient was provided with bilateral hearing aids and initiated speech therapy. He was also at this time submitted to an adenoidectomy and the placement of tympanostomy tubes. After the treatment, speech acquisition progressed within normal standards. At age 3 years, recurrence of the otitis led to a new placement of tympanostomy tubes. Pure-tone audiometry testing was performed at age 6 years and led to a diagnosis of bilateral moderate hearing loss. School performance was normal, although the hearing loss fluctuated in either ear. At age 9 years, the conductive component was absent, however a worsening of the fluctuation and a progression of the sensorineural hearing loss, especially in the right ear, were noted. The progression continued to a point where the hearing aids no longer improved Grant sponsor: Portuguese Fundac ¸ão para a Ciência e Tecnologia