Auditory Phenotypic Variability in Friedreich’s Ataxia Patients

Abstract

Auditory neural impairment is a key clinical feature of Friedreich’s Ataxia (FRDA). We aimed to characterize the phenotypical spectrum of the auditory impairment in FRDA in order to facilitate early identification and timely management of auditory impairment in FRDA patients and to explore the relationship between the severity of auditory impairment with genetic variables (the expansion size of GAA trinucleotide repeats, GAA1 and GAA2), when controlled for variables such as disease duration, severity of the disease and cognitive status. Twenty-seven patients with genetically confirmed FRDA underwent baseline audiological assessment (pure-tone audiometry, otoacoustic emissions, auditory brainstem response). Twenty of these patients had additional psychophysical auditory processing evaluation including an auditory temporal processing test (gaps in noise test) and a binaural speech perception test that assesses spatial processing (Listening in Spatialized Noise-Sentences Test). Auditory spatial and auditory temporal processing ability were significantly associated with the repeat length of GAA1. Patients with GAA1 greater than 500 repeats had more severe auditory temporal and spatial processing deficits, leading to poorer speech perception. Furthermore, the spatial processing ability was strongly correlated with the Montreal Cognitive Assessment (MoCA) score. To our knowledge, this is the first study to demonstrate an association between genotype and auditory spatial processing phenotype in patients with FRDA. Auditory temporal processing, neural sound conduction, spatial processing and speech perception were more severely affected in patients with GAA1 greater than 500 repeats. The results of our study may indicate that auditory deprivation plays a role in the development of mild cognitive impairment in FRDA patients.

Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder

“…Most affected individuals show abnormalities in auditory neural and brainstem responses as a result of auditory neuropathy [92][93][94]. Of FRDA patients, 8 to 13% show sensorineural hearing loss, as revealed in a pure-tone audiogram [95].…”

One-to-one Benefit provided by Antioxidants to cultured skin Fibroblasts from Friedreich Ataxia patients

“…Thus, whether considering the genetic aspects (e.g., size of the expansion in the Frataxin gene or identity of the genes involved, i.e., Frataxin, PIP5K1β), the biochemical aspects (e.g., damage to soluble ISP, to RC components or to antioxidant systems), the clinical signs and the sequence of their apparition, a very contrasting picture between patients emerges. Indeed, this interindividual variability hallmarks the disease in the foreground [3,[20][21][22][23][24][25][26][27][28][29][30][31].…”

Auditory neuropathy in mice and humans with Friedreich ataxia

“…Hearing difficulty is another consistently reported symptom of FRDA. While sound detection is typically normal or near‐normal, 4,5 the majority of affected individuals show progressively disordered firing in the auditory nerve and central auditory pathways (i.e., auditory neuropathy) 4,6,7 . This leads to distortion of auditory temporal cues, impaired localization ability, and abnormal perception of complex acoustic signals such as speech 4,8,9 .…”