A 2-month-old infant fails bilateral otoacoustic emissions (OAE) and auditory brainstem response (AABR) on universal newborn hearing screening. Imaging shows normal cochlear anatomy. Genetic testing reveals biallelic GJB2 mutations. The clinical presentation shown as **A** in the diagram — bilateral profound congenital sensorineural hearing loss (DFNB1) — results from disruption of which physiological process in the inner ear?
A. Endolymph production by the stria vascularis epithelial cells
B. Potassium recycling through gap junctions in the cochlear supporting cells and spiral ligament fibrocytes, essential for maintaining endocochlear potential
C. Vestibular nerve myelination and synaptogenesis in the cochlear nucleus
Calcium influx into outer hair cells during mechanotransduction of sound vibrations
D.
Explanation
Why potassium recycling through gap junctions is correct
GJB2 encodes connexin-26, a transmembrane protein that forms gap junctions in the cochlea. Connexin-26 is expressed in supporting cells, spiral ligament fibrocytes, and suprastrial cells, where it forms a critical network for potassium recycling. During mechanotransduction, K+ enters hair cells and must be recycled back through the gap junction network to the stria vascularis, where it is pumped back into endolymph to maintain the endocochlear potential (+80 mV). Biallelic loss-of-function GJB2 mutations disrupt this potassium recycling pathway, causing collapse of the endocochlear potential and outer hair cell death, resulting in the profound bilateral symmetric SNHL characteristic of DFNB1. This is the single most common genetic cause of autosomal recessive prelingual deafness, accounting for ~50% of severe-to-profound autosomal recessive prelingual genetic deafness. (Cummings Otolaryngology 7e; Smith RJH GeneReviews — DFNB1)
Why each distractor is wrong
Calcium influx into outer hair cells: While calcium is important for hair cell function and mechanotransduction, GJB2 mutations do not directly disrupt calcium channels. The primary pathophysiology of DFNB1 is potassium recycling failure, not calcium dysregulation. Calcium channel mutations cause different forms of hearing loss.
Endolymph production by the stria vascularis: Although the stria vascularis is involved in maintaining endolymph composition, GJB2 mutations do not directly affect strial epithelial cells' endolymph production. The stria vascularis is downstream of the potassium recycling network; it receives recycled K+ to pump back into endolymph. The primary defect is in the recycling pathway itself, not strial production.
Vestibular nerve myelination and synaptogenesis: GJB2 mutations cause non-syndromic hearing loss with normal vestibular function. Children with DFNB1 have normal balance and walk on time. The vestibular nerve and central auditory pathways are intact, which is why cochlear implantation outcomes are excellent. This distractor confuses the auditory and vestibular systems.
High-YieldNEET PG
Connexin-26 (GJB2) gap junctions = potassium recycling in the cochlea; biallelic mutations → endocochlear potential collapse → profound prelingual SNHL (DFNB1), the most common genetic cause of childhood deafness.
Cummings Otolaryngology 7e; Smith RJH GeneReviews — DFNB1 Nonsyndromic Hearing Loss and Deafness 2024
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