Congenital hearing loss

Abstract

Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

Figure 1. Cross-section of the outer, middle and inner ear

The ear is composed of three major parts, the outer, middle and inner ear. The outer ear includes the auricle and external auditory canal, and is separated from the middle ear by the tympanic membrane. The middle ear, a mucosal-lined air-filled space, houses three bones (ossicles) — the malleus, incus and stapes — and bridges the external and inner ear. The inner ear is divided into two parts: the vestibular portion, which includes the vestibule and the three semicircular canals, and the cochlear portion, which contains the outer and inner hair cells of the sensory epithelium. The footplate of the stapes covers the oval window of the inner ear. The VIII cranial nerve (the auditory or cochlear nerve) links the inner ear with the brainstem. The Eustachian tube links the cavity of the middle ear to the pharynx, permitting the equalization of pressure on each side of the tympanic membrane. The ear converts the vibratory mechanical energy of sound into the electrical energy of nerve impulses. Sound is transmitted through the external auditory canal to the tympanic membrane and middle ear ossicles. Here, air vibration is translated and amplified to mechanical vibration. At the level of the footplate, these mechanical vibrations are transmitted to the cochlea, resulting in movement of the cochlear fluids. The movement of the cochlear fluids moves and alters the shape of the outer hair cells of the cochlea. This process mediates sound amplification and increases frequency specificity. The movement of the inner hair cells of the cochlea stimulates the adjacent nerve fibres and transmits the electrical signal to the brain.

Figure 2. The stria vascularis and sensory hair cells

The stria vascularis is the highly specialized tissue that produces the endolymph; it is situated on the lateral wall of the endolymphatic duct in the cochlea, and consists of marginal, intermediate and basal cell layers. On the apical membrane of the marginal cells, ion channels secrete K⁺ into the endolymph against a concentration gradient. Endolymphatic K⁺ flows into sensory hair cells when mechanotransduction (MET) channels on the apical surface of the stereocilia open. The K⁺ influx depolarizes the hair cells and triggers electrical activity in the fibres of the auditory nerve. The hair cells subsequently release K⁺ via channels in the basolateral surface and K⁺ is recycled through one of several pathways back towards the stria vascularis (arrows). ^, The acellular tectorial membrane overlies the sensory hair cells; mutations in genes coding for its various constituents can all cause hearing loss, although not all of these forms of genetic hearing loss are congenital in onset. ^{, ,} The tip link connecting two adjacent stereocilia is located between the apical surface of the shorter one and the lateral surface of the taller one, whereas stereocilin connects the sides of the two stereocilia (top left inset). Mutations in the genes encoding components of the tip links and their interacting proteins might cause syndromic and non-syndromic forms of congenital hearing loss. Unconventional myosin-VIIa, a motor protein that moves along the stereociliary actin filaments, interacts with the PDZ-domain-containing protein harmonin, Usher syndrome type-1G protein and cadherin-23. Cadherin-23 is a long transmembrane molecule that homodimerizes, and its large extracellular domains interact with homodimers of protocadherin-15. These five tip link proteins form the ‘Usher interactome’ and mutations in their coding genes are responsible for Usher syndrome type 1 (Table 1), the most common cause of the dual sensory impairment of hearing and vision loss. Protocadherin-15 forms the lower half of the tip link. Its anchor includes a complex of the motor protein unconventional myosin-XV, its cargo whirlin, epidermal growth factor receptor kinase substrate 8 and calcium and integrin-binding family member 2 (which is also associated with Usher syndrome type 1). ^{, , ,} . The MET channel at the lower tip link density might interact directly with protocadherin-15 (reviewed in Fettiplace & Kim).

Figure 3. Audiometry assessment

A. Pure tone audiometry obtained in a child with bilateral normal hearing thresholds across all frequencies. B. Pure tone audiometry obtained in a child with bilateral and symmetric sensorineural hearing loss. Hearing thresholds are normal up to 1,000 Hz. A ski-slope audiometric configuration is recorded at higher frequencies, showing mild hearing loss at 2,000 Hz that increases to severe hearing loss at 8,000 Hz.

Figure 4. Multidisciplinary algorithm for the assessment of hearing function in infants

Newborns who pass the neonatal hearing screening should undergo regular follow-up when risk factors for hearing loss (as defined by the Task Force of the American Academy of Pediatrics) are present. If a newborn fails the screening and bilateral congenital hearing loss is suspected, a comprehensive audiological and aetiologic work-up is required. Audiological tests can confirm the presence of hearing loss and determine its type (conductive, sensorineural or auditory neuropathy spectrum disorder), laterality and severity. Genetic testing is an integral part of the aetiological work-up, as are the exploration of perinatal insults and the presence of congenital infections as possible causative agents. In particular, timely investigation for congenital cytomegalovirus (CMV) infection is essential, as it is the most common infectious aetiology of hearing loss. Virological identification of CMV must be made in the first 3 weeks of life to ensure that the infection was truly congenital and not post-natally acquired. Imaging studies are recommended in all cases of bilateral hearing loss ≥60 dB or with craniofacial malformations. Imaging exams can rule out the presence of structural inner ear anomalies, which might occur as an independent entity, be part of a syndrome, or have therapeutic implications. Certain inner ear anomalies might place the child at increased risk for sudden hearing loss (for example, enlarged vestibular aqueducts) or meningitis and require appropriate counselling. Imaging studies are a prerequisite before cochlear implantation to assess cochlear anatomy and confirm the presence of a cochlear nerve. A detailed assessment of the test results by a paediatric ophtalmologist is recommended, given the high prevalence (40–60%) of ophthalmologic problems in hearing impaired children. Other complementary investigations include, for example, electrocardiogram and renal ultrasonography. ENT; ear, nose and throat.

Figure 5. Non-medical treatments for hearing loss

A conventional hearing aid converts environmental sounds to amplified sounds. A hard case is worn behind the auricle and contains all the electronic parts (microphone, amplifier and battery). A sound is picked up by a microphone and converted to an electrical signal that corresponds to the pressure variation produced by the sound. This signal is then amplified and delivered to a speaker that converts the amplified electrical signal back to sound. The speaker sends the sound signal to the tympanic membrane by a slim tube connecting the hearing aid to an earmold that fits in the external auditory canal. B. A cochlear implant converts sounds to electrical signals and is composed of different parts. A microphone (1) picks up environmental sounds and transmits them to a speech processor. Through a magnetic coil (3), acoustic signals are transmitted from the speech processor to a subcutaneously implanted receiver/stimulator (4) that converts the acoustic signal into electric impulses. An electrode array (5) placed in the scala tympani of the cochlea directly stimulates electrically the auditory nerve (6). C. A bone-anchored hearing aid converts a sound signal to micro-vibrations: it uses the principle of bone conduction to directly stimulate the cochlear fluids by vibrating the skull behind the ear at auditory frequencies. A titanium screw (the implant) is surgically anchored in the bone and becomes fixed through a process called osseo-integration. The implant is connected to a sound transducer by means of an abutment (connector). The sound transducer captures the sound, converts it to vibrations and sends them to the implant. The implant then transmits the vibrations through the bone directly to the inner ear. In the most recent bone-anchored hearing aid systems, the abutment is replaced by a magnetic connection. Copyright permission obtained from Cochlear Limited ©