TY  - JOUR
AU  - Mobarakeh, Zahra Iran Pour
AU  - Heidari, Parisa
AU  - Amiri, Marzieh
PY  - 2026
DA  - 2026/10/29
TI  - Temperature-Sensitive Auditory Neuropathy: A Scoping Review of Clinical, Genetic, and Neurobiological Evidence
JO  - OBM Neurobiology
SP  - 359
VL  - 10
IS  - 04
AB  - Temperature-sensitive auditory neuropathy (TSAN) is a rare and clinically distinct subtype of auditory neuropathy. TSAN is characterized by reversible deterioration of auditory neural function during hyperthermic states despite well-preserved cochlear outer hair cell activity. Although several case reports, familial studies, and experimental investigations have described this disorder, the available evidence remains inconclusive. This scoping review integrates clinical, genetic, and neurobiological evidence on TSAN, sheds light on its underlying mechanisms, and explores genotype-phenotype correlations. A comprehensive search of PubMed, PMC, Scopus, Web of Science, and Google Scholar was conducted up to December 2025. Studies reporting temperature-dependent auditory dysfunction consistent with TSAN were included regardless of their study design. Eligible publications comprised case reports, case series, familial cohorts, genetic studies, and mechanistic investigations. We narratively synthesized the extracted study data because of their methodological heterogeneity. Thirteen studies met the inclusion criteria and were grouped into clinical, genetic, and mechanistic studies. Clinically, TSAN is characterized by preserved otoacoustic emissions and/or cochlear microphonics with absent or severely abnormal auditory brainstem responses during hyperthermia. Hearing thresholds and speech perception typically deteriorate during febrile episodes and often improve following temperature normalization. Genetic evidence supports an autosomal recessive OTOF-related basis in reported TSAN cases, with temperature-sensitive phenotypes more frequently reported in genotypes containing certain non-truncating variants. Mechanistic evidence across molecular, synaptic, cortical, and translational levels supports a model of temperature-dependent presynaptic dysfunction, including impaired otoferlin-mediated synaptic vesicle release and altered neural synchrony. TSAN represents a temperature-dependent presynaptic synaptopathy in which thermal vulnerability of synaptic proteins, particularly otoferlin, may contribute to reversible neural dysfunction. Integration of clinical, genetic, and experimental data supports a coherent neurobiological framework with important consequences for diagnosis, genetic counseling, and translational auditory neuroscience.
SN  - 2573-4407
UR  - https://doi.org/10.21926/obm.neurobiol.2604359
DO  - 10.21926/obm.neurobiol.2604359
ID  - Mobarakeh2026
ER  -