-Related Hearing Loss

CLINICAL CHARACTERISTICS

-related hearing loss is an auditory synaptopathy that results from defective synaptic transmission from normally functioning cochlear inner hair cells (IHCs) to the auditory nerve. Thus, newborn hearing screening (NBHS) that relies on otoacoustic emission (OAE) testing, which primarily assesses function of outer hair cells (OHCs), is usually normal, whereas hearing tests that rely on auditory brain stem response (ABR) testing are abnormal given the failure of signal transmission from IHCs to the auditory nerve. All individuals with -related hearing loss have severely impaired speech discrimination. The two phenotypes comprising -related hearing loss are typical -related hearing loss and atypical -related hearing loss. Typical -related hearing loss is characterized by congenital or prelingual, typically severe-to-profound bilateral hearing loss (70 to ≥90 dB) associated with normal OAEs and abnormal ABRs. With age, OAEs decrease or disappear in 20%-80% of individuals. Atypical -related hearing loss is characterized by either temperature-sensitive -related hearing loss or progressive -related hearing loss. Temperature-sensitive -related hearing loss is characterized by hearing that ranges from normal hearing to moderate hearing loss (0-55 dB) at baseline body temperature and declines to bilateral hearing loss ranging from severe (71-90 dB) to profound (>90 dB) with an elevation of body temperature (approximately 0.5 °C or more). The increased hearing loss resolves typically within hours of baseline body temperature returning to normal. Progressive -related hearing loss ranges from mild to moderate at onset, and over the course of a few months or years could progress to profound. Rate of hearing loss progression is variable.

DIAGNOSIS/TESTING: The diagnosis of -related hearing loss is established in a proband with suggestive findings and biallelic pathogenic variants in identified by molecular genetic testing.

MANAGEMENT

There is no cure for -related hearing loss. Early auditory intervention is critical to the development of speech and language. Habilitation options are tailored to the degree and frequency of hearing loss. While hearing aids may be trialed in persons with mild-to-severe hearing loss, these are unlikely to be beneficial due to auditory synaptopathy being the underlying cause. In contrast, cochlear implants may provide clinical benefit because they bypass the dysfunctional synapse and stimulate the auditory nerve directly. Educational and early intervention programs designed for individuals with hearing loss should start as early as possible. For individuals with atypical temperature-sensitive -related hearing loss, prevent febrile episodes and avoid exercise and/or ambient conditions that would cause body temperature to rise. Treat febrile episodes as quickly as possible. : To monitor the individual's response to supportive care and the emergence of new manifestations, the primary focus should be routine audiometric follow up. The frequency of follow up should be individualized and is likely to vary over time. For individuals with temperature-sensitive -related hearing loss, prevent fevers and other activities/ambient conditions that would cause body temperature to rise. It is appropriate to clarify the genetic status of apparently asymptomatic sibs of a proband shortly after birth by molecular genetic testing for the pathogenic variants found in the proband so that appropriate early support and management can be provided to the child and family.

GENETIC COUNSELING

-related hearing loss is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an pathogenic variant, each sib of an affected individual has at conception a 25% chance of having -related hearing loss, a 50% chance of being a carrier and not having -related hearing loss, and a 25% chance of not being a carrier and not having -related hearing loss. Once the pathogenic variants have been identified in a family member with -related hearing loss, prenatal and preimplantation genetic testing for -related hearing loss are possible.