The Ear

The auditory system bears one of the most intricate mechanisms of sensation ability in humans. The inner ear, a fluid-filled organ, is responsible for transforming the mechanical energy of the sound waves into electrical stimuli, which will eventually be translated in the brain. Anatomically, the inner ear is divided into the auditory and vestibular systems. While the auditory system is responsible for sound sensation, the vestibular system is responsible for three dimensional orientation and gravity perception. The similarities between these two systems often leads to balance disorders in hearing impaired individuals. The auditory system is composed of a snail-shaped cochlea. The cochlea is a fluid-filled tube coiled in a spiral shape around the modiolus. Upon viewing a longitudinal cross section, the cochlear canal is divided into three compartments (scalae). The scala media filled with endolymph, lies between two larger perilymphatic filled compartments, the scala vestibuli and scala tympani.

Genetics of deafness

Given the complexity of the hearing mechanism, it should come as no surprise that a panoply of genes have been discovered to be involved in hearing loss. To date, more than 50 genes and 80 additional loci have been linked to various degrees of hearing impairment (Figure 2). Taking advantage of standardized nomenclature, a common classification of the loci and genes for hearing impairment has been established (HUGO Gene Nomenclature Committee). Depending on the inheritance mode, the nonsyndromic genes or loci are classified accordingly: DFNA (dominant), DFNB (recessive), DFNX (X-linked), DFNY (Y-linked), and DFNM (modifier). Additional specific symbols are used for different forms of hearing loss including otosclerosis (OTSC), auditory neuropathy (AUNA), and mitochondrial (MRTNR, MTTS) genes. For each locus, the relevant symbol is depicted with a number next to it, designated by the chronological order of its discovery. Routinely updated, the Hereditary Hearing Loss Homepage provides an open and reliable resource for all listed genes and loci.

Causes of hearing loss

Similar to other sensory loss, hearing impairment has a wide spectrum of etiologies originating from both environmental and genetic factors. Prolonged exposure to high intensity sound poses high risk for auditory function and can lower hearing thresholds. Acoustic trauma, as a result of a sudden loud noise, can lead to temporary and/or permanent hearing impairment. Among environmental factors, different viral infections, as well as neonatal anoxia and hyperbilirubinemia, can also cause permanent hearing defects. Long term augmentation of ototoxic drugs such as aminoglycoside and gentamicin antibiotics has an adverse effect on the auditory system and accounts for hearing defects. Unlike the genetics factors dictated by hereditary information, some of the environmental factors can be reduced and avoided by raising awareness for appropriate protection.

Genetic insults contributing to hearing defects poses greater challenges. The clinical heterogeneity of hearing loss is characterized by common classifications based on several parameters such as onset, severity and the presence of additional clinical manifestations other than deafness. Hearing loss that occurs prior to speech acquisition is termed prelingual deafness, either congenital or appearing after birth. A hearing disability that appears early in childhood can have a major consequence on language acquisition. Age related hearing loss (ARHL) affects the elderly population with high prevalence and its appearance and progression is influenced by both genetic and environmental factors. About 60% of the population over the age of 65 suffers from different degrees of hearing loss, with a decline in sensitivity to sound, accompanied with reduced speech perception. Hearing loss is also categorized based on the frequency loss and the severity of hearing thresholds. High tone loss refers to reduced sensitivity of high frequency acoustic stimulus, as opposed to low tone loss for the low frequencies. The terms profound, mild and moderate describe the descending order of different severity levels of hearing impairments. When hearing loss is the only apparent abnormality, it is referred to as non-syndromic hearing loss (NSHL). In other cases hearing loss occurs along with a variety of other malformations and thus is designated as syndromic hearing loss (SHL).