Does bilirubin protect outer hair cells (OHCs) from the damage induced by mutations in the connexin 26 gene?

Background: Auditory neuropathy (AN) is a disorder characterized by the impairment of the auditory periphery in the presence of preserved functions of cochlear outer hair cells (OHCs). In affected subjects, brainstem activities recorded as far-field potentials from surface electrodes are typically undetectable whereas OHCs activities (otoacoustic emissions and/or cochlear microphonics) are normal. The disorder occurs with a wide range of etiologies. Recently, the clinical picture of AN has been identified in individuals with mutations in the connexin 26 gene (GJB2). Study design: Two children having distortion product otoacoustic emissions and absent brainstem responses were submitted to transtympanic electrocochleography (ECochG) with the aim of evaluating the auditory peripheral function with a near-field recording technique. Subject 1 (12 month old girl) was GJB2 homozygote with the genotype 35delG/35delG. Her history was also remarkable for neonatal hyperbilirubinemia (20.2 mg/100ml). Subject 2 was a 15 month old girl carrying the GJB2 mutation M34T in heterozygosis. She had developed jaundice at birth due to increased bilirubin levels (11.2 mg/100ml). Results: On the ECochG recording both children showed the cochlear microphonic (CM) with an amplitude which was comparable to that obtained in normally-hearing ears. No compound action potential (CAP) nor summating potential was identified in subject 1. The ECochG recordings collected from both ears in subject 2 showed a broad CAP with 50 dB nHL threshold, which was delayed in latency and reduced in amplitude compared to that obtained from normally-hearing ears. Conclusions: The clinical picture of AN in patients with mutations in the connexin 26 gene is underlain by lesion involving inner hair cells and/or auditory nerve terminals. We propose that neonatal hyperbilirubinemia could play a role in protecting the OHCs function against the damage induced by the GJB2 gene mutations.