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Dante Labs US Report

Pendred Syndrome

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Pendred Syndrome is the most common form of congenital bilateral deafness and is accompanied by euthyroid goiter (benign thyroid hypertrophy not associated with altered hormone levels). Transmitted with an autosomal recessive modality, in affected subjects it can also lead to the appearance of vestibular dysfunctions (the vestibular apparatus, located in the inner ear, allows to maintain the balance of the body especially during movements).
The typical characteristic of Pendred Syndrome is the so-called Mondini malformation, given by the combination of widening of the vestibular aqueduct and deformity of the cochlea.
The main mutations leading to Pendred Syndrome affect the functionality of pendrin, a protein expressed in the inner ear, breast, testes, kidney and thyroid. Hence the manifestations also affecting this gland, apparently far from the sensorineural deafness found in Pendred. This protein acts as a transporter of ions (including chloride and bicarbonate), giving rise to tissue-specific effects: in the inner ear it guarantees the right endolymphatic pressure and in the thyroid it regulates the transport of iodine, essential for the synthesis of thyroid hormones. While in the inner ear changes in pendrin are not compensated by other mechanisms (thus giving rise to the deafness of Pendred Syndrome), in the thyroid iodine can be carried by more transporters (hence the euthyroid phenotype that of the affected subjects) .
Progressive hearing loss in affected subjects can manifest itself from birth or in the first years of life, worsening over time and representing a serious obstacle to language acquisition. Some children become completely deaf.

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