A 12-year-old boy from a consanguineous family presents with progressive bilateral sensorineural hearing loss. Audiometry shows the pattern marked **B** in the diagram. On imaging, an enlarged vestibular aqueduct (EVA) is confirmed, and thyroid examination reveals a firm goiter. Genetic testing reveals biallelic mutations in the SLC26A4 gene. Which of the following best describes the pathophysiologic basis of the hearing loss pattern seen at **B**?

Question

Accepted Answer

A. Pendrin-mediated disruption of endolymphatic ion homeostasis leading to endolymphatic hydrops and hair cell loss. ## Why "Pendrin-mediated disruption of endolymphatic ion homeostasis leading to endolymphatic hydrops and hair cell loss" is right

The reverse-slope low-frequency SNHL pattern marked **B** is the characteristic audiometric signature of Pendred syndrome. This pattern results directly from biallelic SLC26A4 mutations encoding pendrin, a chloride/iodide/bicarbonate transporter. Pendrin is essential for endolymphatic ion homeostasis in the cochlea; its deficiency disrupts electrolyte balance, triggering endolymphatic hydrops and progressive sensorineural hair cell loss. The clinical triad of bilateral SNHL, euthyroid goiter (from impaired thyroid iodide organification), and enlarged vestibular aqueduct on imaging confirms Pendred syndrome. The reverse-slope audiogram reflects the specific cochlear pathophysiology of pendrin deficiency (Smith GeneReviews Pendred 2017).

## Why each distractor is wrong

- **Stapes fixation from otosclerotic bone remodeling at the oval window**: This produces a conductive or mixed hearing loss with a Carhart notch (marked **C** in the diagram), not sensorineural loss. Otosclerosis is not associated with EVA or SLC26A4 mutations.
- **Selective damage to outer hair cells in the basal turn from noise exposure**: Noise-induced hearing loss produces a high-frequency notch (around 4 kHz), not the reverse-slope pattern. It is not hereditary, does not cause goiter, and is not linked to EVA.
- **Age-related degeneration of cochlear neurons in the apical turn**: Presbycusis produces a high-frequency sloping loss (marked **A** in the diagram), not reverse-slope. It is not associated with goiter, EVA, or genetic mutations in SLC26A4.

**High-Yield:** Pendred syndrome = SLC26A4 mutations + reverse-slope SNHL + EVA on CT + euthyroid goiter; avoid head trauma and contact sports to prevent stepwise hearing decline.

[cite: Smith GeneReviews Pendred 2017; Mondini malformation imaging]

Answer

B. Age-related degeneration of cochlear neurons in the apical turn

Answer

C. Stapes fixation from otosclerotic bone remodeling at the oval window

Answer

D. Selective damage to outer hair cells in the basal turn from noise exposure

Explanation

Why "Pendrin-mediated disruption of endolymphatic ion homeostasis leading to endolymphatic hydrops and hair cell loss" is right

Why each distractor is wrong

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