Auditory neuropathy is characterized by abnormal neural conduction in the auditory pathway despite normal outer hair cell function, exhibiting substantial genetic heterogeneity and phenotypic variability. We report the case of a 29-year-old male patient with hearing loss, bilateral enlargement of the vestibular aqueduct (EVA), and vestibular system dysfunction. Based on these features, which are tipically indicative of Pendred syndrome, a molecular investigation including the SLC26A4 gene was performed. This analysis identified a novel heterozygous missense variant, c.411A>C, in exon 4 of the DIAPH3 gene, likely associated with autosomal dominant auditory neuropathy. This point mutation results in substituting glutamic acid with aspartic acid at position 137 p.(Glu137Asp), in the functional Rho-GTPase-binding domain of the DIAPH3 protein. Segregation analysis of the parents and two siblings of the proband revealed the variant’s de novo origin. According to the American College of Medical Genetics and Genomics criteria, this finding underscores the need to reclassify the variant as likely pathogenic. This is the first evidence of an association between a DIAPH3 variant and hearing loss coupled with bilateral EVA and vestibular system dysfunction. This finding contributes to a better understanding of the phenotypic complexity of disorders grouped within the auditory neuropathy spectrum.

Auditory neuropathy is characterized by abnormal neural conduction in the auditory pathway despite normal outer hair cell function, exhibiting substantial genetic heterogeneity and phenotypic variability. We report the case of a 29-year-old male patient with hearing loss, bilateral enlargement of the vestibular aqueduct (EVA), and vestibular system dysfunction. Based on these features, which are tipically indicative of Pendred syndrome, a molecular investigation including the SLC26A4 gene was performed. This analysis identified a novel heterozygous missense variant, c.411A>C, in exon 4 of the DIAPH3 gene, likely associated with autosomal dominant auditory neuropathy. This point mutation results in substituting glutamic acid with aspartic acid at position 137 p.(Glu137Asp), in the functional Rho-GTPase-binding domain of the DIAPH3 protein. Segregation analysis of the parents and two siblings of the proband revealed the variant’s de novo origin. According to the American College of Medical Genetics and Genomics criteria, this finding underscores the need to reclassify the variant as likely pathogenic. This is the first evidence of an association between a DIAPH3 variant and hearing loss coupled with bilateral EVA and vestibular system dysfunction. This finding contributes to a better understanding of the phenotypic complexity of disorders grouped within the auditory neuropathy spectrum.

Auditory neuropathy is characterized by abnormal neural conduction in the auditory pathway despite normal outer hair cell function, exhibiting substantial genetic heterogeneity and phenotypic variability. We report the case of a 29-year-old male patient with hearing loss, bilateral enlargement of the vestibular aqueduct (EVA), and vestibular system dysfunction. Based on these features, which are tipically indicative of Pendred syndrome, a molecular investigation including the SLC26A4 gene was performed. This analysis identified a novel heterozygous missense variant, c.411A>C, in exon 4 of the DIAPH3 gene, likely associated with autosomal dominant auditory neuropathy. This point mutation results in substituting glutamic acid with aspartic acid at position 137 p.(Glu137Asp), in the functional Rho-GTPase-binding domain of the DIAPH3 protein. Segregation analysis of the parents and two siblings of the proband revealed the variant’s de novo origin. According to the American College of Medical Genetics and Genomics criteria, this finding underscores the need to reclassify the variant as likely pathogenic. This is the first evidence of an association between a DIAPH3 variant and hearing loss coupled with bilateral EVA and vestibular system dysfunction. This finding contributes to a better understanding of the phenotypic complexity of disorders grouped within the auditory neuropathy spectrum.