Audiologia&Foniatria

Hearing loss is the most common sensorineural disorder, affecting approximately 1:1000 new-borns. In developed countries, more than half of the cases of congenital hearing loss are due to genetic causes and both syndromic and non-syndromic forms may be recognized. Approximately 20% of the cases of nonsyndromic hearing loss are inherited according to an autosomal dominant pattern. Autosomal dominant hereditary hearing loss (ADHHL) is characterized by a wide genetic heterogeneity and by inter- and intrafamilial clinical variability, making genotype-phenotype correlations extremely complicated. Here we describe a large multi-generation Italo-American kindred affected by ADHHL. After a complete clinical evaluation and hearing function assessment through pure tone audiometry, the proband underwent a multiple-step genetic testing. Eventually, whole exome sequencing was performed on his and other selected family members’ DNA leading to the identification of a heterozygous missense variant in the TBC1D24 gene. Mutations in this gene have been associated with a variety of conditions that are inherited in an autosomal recessive pattern and that may or may not include hearing loss. Interestingly, the variant identified in our kindred is the only mutation in the TBC1D24 gene that has been associated with ADHHL in previous studies. Our case report confirms the role of the TBC1D24 gene and specifically of the p.(S178L) variant in the etiopathogenesis of ADHHL, underlining once again the clinical variability associated with variants in this gene.