Pendred syndrome

Although precise prevalence is unknown, PDS may account for up to 7.5% of cases of congenital hearing loss (ORPHA:705).

Pendred syndrome is inherited in an autosomal recessive manner. Both parents of an affected individual are typically heterozygous carriers; the recurrence risk for siblings is 25% in each pregnancy. Carrier testing of at-risk relatives requires prior identification of the familial pathogenic variants. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

Pendred syndrome is diagnosed primarily by molecular genetic testing. Imaging (CT or MRI) typically demonstrates bilateral enlargement of the vestibular aqueduct (midpoint diameter of the Although precise prevalence is unknown, PDS may account for up to 7.5% of cases of congenital hearing loss (ORPHA:705). endolymphatic duct ≥1.0 mm or operculum ≥2.0 mm), often accompanied by incomplete cochlear partition type II. The perchlorate discharge test, which detects the iodide-organification defect, is the most sensitive biochemical marker but is now rarely used in clinical practice.

Main differential diagnoses include:

• Hereditary distal renal tubular acidosis with sensorineural hearing loss: autosomal recessive SNHL with EVA, accompanied by metabolic acidosis from renal tubular acidosis; ATP6V0A4, ATP6V1B1, FOXI1
• Branchiootorenal spectrum disorder: autosomal dominant SNHL with EVA and cochlear hypoplasia, branchial fistulae or cysts, outer- and middle-ear malformations, and renal malformations; EYA1, SIX1
• Treacher Collins syndrome: predominantly conductive hearing loss with craniofacial features (maxillary hypoplasia, micrognathia, eyelid coloboma); TCOF1, POLR1B, POLR1C, POLR1D

• Establishing the molecular diagnosis confirms the clinical suspicion and enables informed genetic counselling of the affected individual and their family.
• Confirmation of the molecular diagnosis is the prerequisite for specific and individualised surveillance and targeted clinical management, the nature and timing of which are determined by the treating physicians in consultation with the affected individual.
• Identification of the familial pathogenic variants enables predictive and carrier testing of at-risk relatives within the framework of human-genetic counselling.

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