A 7-year-old girl from rural Maharashtra presents with progressive bilateral hearing loss since age 3 years, with recent fluctuation in hearing acuity following a minor head trauma during play. Examination reveals a diffuse, non-tender thyroid enlargement. High-resolution CT temporal bone shows enlarged vestibular aqueducts bilaterally and incomplete partition of the cochlea (Mondini dysplasia). Audiometry demonstrates the pattern marked **A** in the diagram — sensorineural hearing loss that is more severe at low frequencies than at high frequencies. Which of the following best explains the pathophysiology of the hearing loss pattern marked **A** in this patient?

Explanation

## Why option 1 is correct Pendred syndrome is the most common syndromic cause of congenital hearing loss (~7–10% of hereditary deafness) and is caused by autosomal recessive mutations in the SLC26A4 gene, which encodes pendrin — an anion (iodide/chloride/bicarbonate) exchanger. Pendrin is expressed at the apical membrane of inner ear cells in the endolymphatic sac and stria vascularis, where it regulates endolymph composition. Defective pendrin leads to abnormal endolymph homeostasis, resulting in enlarged vestibular aqueduct (EVA) and Mondini-type cochlear dysplasia. This pathophysiology produces the characteristic reverse-slope sensorineural hearing loss (worse at low frequencies, marked **A**) — a pattern distinct from presbycusis or noise-induced loss. The combination of fluctuating/progressive SNHL, euthyroid goitre (from iodide organification defect in the thyroid), and imaging findings of EVA + Mondini dysplasia is pathognomonic for Pendred syndrome. ## Why each distractor is wrong - **Option 2 (Noise-induced cochlear damage)**: Noise exposure causes high-frequency sensorineural loss (basal cochlear damage), not reverse-slope loss. There is no occupational history in a 7-year-old child, and noise-induced loss does not present with goitre or EVA. - **Option 3 (Presbycusis)**: Age-related hearing loss is a high-frequency sloping pattern due to strial and spiral ligament degeneration, not reverse-slope loss. Presbycusis occurs in elderly patients, not children, and is not associated with goitre or cochlear dysplasia. - **Option 4 (GJB2 connexin-26 mutation)**: GJB2 mutations cause nonsyndromic sensorineural hearing loss, typically with a high-frequency sloping or flat pattern, not reverse-slope loss. GJB2 defects do not cause goitre, EVA, or Mondini dysplasia, and are not associated with thyroid pathology. **High-Yield:** Pendred syndrome = SLC26A4 mutation → reverse-slope SNHL + euthyroid goitre + EVA + Mondini dysplasia; avoid head trauma (risk of sudden hearing loss in EVA). [cite: Dhingra ENT 7e Ch 18; Harrison 21e Ch 30]