Genetic Sensorineural Hearing Loss

Volumes of texts and journals are dedicated to the pathophysiology of genetic hearing loss and can not be easily summarized in a few paragraphs. Interestingly, note that as our understanding of the molecular basis of genetic hearing loss increases, so does our understanding of the molecular basis of hearing itself, although it remains still largely unsolved.[3, 4]

First, we must understand that genetic hearing loss seems to breach all categories of hearing loss, including the following: congenital, progressive, and adult onset; conductive, sensory, and neural; syndromic and nonsyndromic; high-frequency, low-frequency, or mixed frequency; and mild or profound. Genetic hearing loss may show patterns of recessive, dominant, or sex-linked inheritance and may be a result in mutation of both cellular or mitochondrial DNA (and RNA, in the case of mitochondrial genes). Genetic hearing loss may be subject to environment and aging, such as noise-induced or age-induced hearing loss.

New genetic mutations are linked to hearing loss every year. More than 100 loci have been identified involving genes that code for proteins involved in the structure and function of hair cells, supporting cells, spiral ligament, stria vascularis, basilar membrane, spiral ganglion cells, auditory nerve, and virtually every structural element of the inner ear.[5]

See the image below.

Dysfunctional proteins have been identified in the impaired molecular-physiologic processes of potassium and calcium homeostasis,[6] apoptotic signaling,[7] stereocilia linkage,[8] mechanicoelectric transduction, electromotility, and other processes.[3] Eisen and Ryugo provide an excellent review of the molecular pathophysiology of genetic hearing loss.[3]

Frequency

United States

Between 2011 and 2012, the overall annual prevalence of hearing loss in the United States was 16% (27.7 million) among adults aged 20-69 years, a slight decrease from the annual prevalence of 16% (28.0 million) between 1999 and 2004. Moreover, at birth approximately 2-3 children per 1000 in the United States have detectable hearing loss.[9]

Congenital hereditary hearing loss must be differentiated from acquired hearing loss. More than half of all cases of prelingual deafness are genetic. The remaining 40-50% of all cases of congenital hearing loss are due to nongenetic effects, such as prematurity, postnatal infections, ototoxic drugs, or maternal infection (with cytomegalovirus [CMV] or rubella). Most cases of genetic hearing loss are autosomal recessive and nonsyndromic. Hearing loss that results from abnormalities in connexin 26 and connexin 30 proteins likely account for 50% of cases of autosomal recessive nonsyndromic deafness in American children.

The incidence of hearing loss increases with age. In the United States, hearing loss exists in about one in three people between the ages of 65 and 74 years and in almost 50% of those older than 75 years.[10] Adult-onset hearing loss can be attributed to normal aging processes and environmental triggers. However, an individual's genetic predisposition should not be underestimated, as illustrated by aminoglycoside-induced ototoxicity and the predisposition to noise-induced hearing loss.

Current statistics can be found on the Early Hearing Detection & Intervention (EHDI) Program Web site published by the Centers for Disease Control and Prevention.

International

More than 1.5 billion people worldwide suffer from hearing loss, according to the World Health Organization (WHO).[11] Genetic sensorineural hearing loss (SNHL) appears to occur twice as often in developed countries as in underdeveloped countries. In addition to ancestry and race, the proportions of hereditary versus acquired and syndromic versus nonsyndromic hearing loss across populations is highly variable and is heavily influenced by multiple factors, some likely not yet identified, including drift of populations, frequency of consanguinity, and health status.

Estimating the prevalence of hereditary hearing loss in populations across the world is very difficult because access to health care, poor health conditions, and a low level of awareness of hearing loss is compounded by a higher frequency of complicating risk factors such as neonatal distress, prematurity, high fever, otitis media, meningitis, ototoxic medications, and illnesses such as rubella.[12]

Saunders et al demonstrated a prevalence of significant hearing loss of 18% in a group of school-aged children in rural Nicaragua, with a familial history of hearing loss in 24% of the children with hearing loss.[12] Large-scale epidemiologic studies are needed and will become more feasible as molecular testing is made available to the world’s populations.

Race

Genetic hearing loss does have significant ethnic links. Angeli recently reviewed the ethnic variability of DGNB1 and showed greater allelic variability in Hispanics.[13] Schimmenti et al showed a lower prevalence of connexin-related hearing loss in Hispanic infants.[14]

Age

Before universal hearing screening for newborns, less than 50% of children who had hearing impairment were identified before the age of 3 years. Detection of risk factors (eg, prematurity, low birth weight, low Apgar scores) helps in identifying less than 50% of infants who have or who are at risk for hearing loss. In one study, 78% of infants identified with hearing loss were in the well-baby nursery and not the neonatal intensive care nursery.[15] This finding emphasized the ineffectiveness of screening on the basis of risk identification alone. Neonatal hearing screening is required in at least 45 states, resulting in earlier identification and treatment of hearing impairment.[16] Hereditary hearing loss may also be progressive or adult in onset.

Genetic hearing loss may be congenital, prelingual, or postlingual in onset and may present with progressive, fluctuating, or stable patterns. Congenital hearing loss is potentially identifiable with newborn screening. High-risk indicators should be used to identify children who are at risk for developing hearing loss after birth. Attention to high-risk indicators, to achievement of speech and language milestones, and to the family history are essential in evaluating a child for hearing loss.

Failure to achieve the following speech and language milestones may indicate hearing loss and necessitate a hearing evaluation:[17]

• Birth to 3 months

  • Startles to loud noise

  • Awakens to sounds

  • Blinks or widens eyes in response to noises

• 3-4 months

  • Quiets to mother's voice

  • Stops playing, listens to new sounds

  • Looks for source of new sounds that are not in sight

• 6-9 months

  • Enjoys musical toys

  • Coos and gurgles with inflection

  • Says "mama"

• 12-15 months

  • Responds to his or her name and the word "no"

  • Follows simple requests

  • Uses expressive vocabulary of 3-5 words

  • Imitates some sounds

• 18-24 months

  • Knows body parts

  • Uses expressive vocabulary with 2-word phrases (minimum of 20-50 words)

  • 50% of speech intelligible to strangers

• By 36 months

  • Uses expressive vocabulary of 4- to 5-word sentences (approximately 500 words)

  • 80% of speech intelligible to strangers

  • Understands some verbs

Potential sources of acquired hearing loss should be considered including the following: in utero infection associated with genetic sensorineural hearing loss (SNHL; eg, toxoplasmosis, rubella, CMV infection, herpes, syphilis), hyperbilirubinemia at levels that require exchange transfusion, birth weight of less than 1500 g, bacterial meningitis, low Apgar scores (0-3 at 5 minutes, 0-6 at 10 minutes), respiratory distress (eg, due to meconium aspiration), mechanical ventilation for more than 10 days, and exposure to ototoxic medication (eg, gentamicin) administered for more than 5 days or used in combination with loop diuretics.

In older children, additional confounding factors include otitis media, mumps, measles, and head trauma. A history of visual impairment, syncope spells, kidney disease, or other system issues should be identified as potential indicators of a syndromic etiology. A detailed family history to identify affected parents, siblings, and relatives is imperative in the evaluation of the patient with hearing impairment.

Because genetic sensorineural hearing loss (SNHL) is associated with effects on virtually every organ, the physician must be familiar with the constellation of physical findings that may elucidate the etiology of a patient's hearing impairment.

Physical examination should include a complete evaluation of the ears, nose, throat, head, and neck, along with an overall assessment of the child's general physical and neurologic status.

Findings associated with hearing loss include microtia or atresia of the ear canal, cleft lip or palate, craniofacial abnormalities (eg, micrognathia, facial asymmetry, microcephaly, or craniosynostosis), cranial nerve weakness, heterochromia of the iris or other abnormalities of the ocular structures, vision impairment, goiter, and skeletal abnormalities.

Approximately 50% of all cases of congenital deafness are genetic. Approximately 70% of cases of hereditary deafness are nonsyndromic, and the remaining 30% are syndromic, associated with specific deformities or medical problems. Of nonsyndromic hearing losses, 75-85% are inherited in an autosomal recessive pattern, 15-20% are inherited in an autosomal dominant pattern, and 1-3% are inherited in an X-linked pattern. Genetic hearing loss is differentiated from acquired hearing loss with identification of a perinatal infection, such as toxoplasmosis, rubella, cytomegalovirus and herpes (TORCH), or another source such as trauma or noise. Although generally thought of as a childhood condition, genetic hearing loss can result in adult-onset hearing loss. A genetic basis or a genetic-environmental interaction appears to predispose some patients to noise or age-related hearing loss.

Syndromic hearing impairment

More than 400 genetic syndromes are associated with hearing impairment. These disorders are categorized as autosomal dominant, recessive, or X-linked.

Syndromic hearing impairment, autosomal dominant

Waardenburg syndrome

Waardenburg syndrome is the most common cause of autosomal dominant syndromic hearing loss.[18] The syndrome includes dystopia canthorum, a broad nasal root, confluence of the medial eyebrows, heterochromia irides, a white forelock, and bilateral or unilateral SNHL. Expressivity is extremely variable. Four subtypes of Waardenburg syndrome are defined, as follows:

• Type I includes dystopia canthorum (ie, lateral displacement of the inner canthus of the eye) and is caused by mutations in PAX3.

• Type II is characterized by the absence of dystopia canthorum and is caused by mutations in MITF.

• Type III has associated upper-limb abnormalities and is caused by mutations in PAX3.

• Type IV is thought to be caused by mutations in EDNRB, EDN3, and SOX10, and patients with type IV have Hirschsprung disease.

Branchio-oto-renal syndrome

Branchio-oto-renal syndrome is the second most common cause of autosomal dominant syndromic HL. This condition manifests as renal abnormalities, preauricular pits, deformed auricles, and lateral branchial cysts. The hearing loss may be conductive, SNHL, or mixed. Some patients have Mondini anomalies of the cochlea. Penetrance is high, but expressivity is extremely variable. Mutations in the EYA1, SIX1, and SIX5 genes have been identified.

Gigante et al described the first known case of branchio-oto-renal syndrome associated with focal glomerulosclerosis, occurring in a patient with a novel EYA1 splice site mutation. The patient had hearing loss, preauricular pits, branchial fistulae, and hypoplasia of the left kidney. The splice site mutation, c.1475 + 1G > C, was found through mutational analysis of EYA1.[19]

Neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is associated with vestibular schwannomas, meningiomas, ependymomas, juvenile cataracts, and other intracranial and spinal tumors. The gene for NF2 has been mapped to chromosome 22q12.2 and is thought to be a tumor-suppressor gene. It has about 50% penetrance. In the Wishart type of NF2, the disease manifests in childhood or early adulthood. As vestibular schwannomas and other tumors develop, this subtype becomes rapidly progressive and often severely disabling. In the Gardner type of NF2, disease is more limited, less disabling, and presents later (in the third or fourth decades) than it does in the Wishart type.[20]

A literature review by Chung et al indicated that in NF2, stereotactic radiosurgery (SRS) can safely and effectively serve as an alternative to surgery in the treatment of vestibular schwannomas. While surgery led to a greater mean hearing preservation rate than SRS (52.0% vs 40.1%, respectively), SRS was associated with a higher mean facial nerve preservation rate than surgery (92.3% vs 75.7%, respectively).[21]

Sticker syndrome

Sticker syndrome is defined by the association of cleft palate, progressive genetic sensorineural hearing loss (SNHL), and spondyloepiphyseal dysplasia (SED). Defects in COL result in 3 different types STL1 (COL2A1), STL2 (COL11A1), and STL3 (COL11A2). Related morbidity of SED includes atlantoaxial instability, scoliosis, osteoarthritis, myopia, and retinal detachment.

Otosclerosis

Otosclerosis is a genetic disorder generally associated with adult-onset conductive hearing loss. However, advanced otosclerosis may cause SNHL. The genes responsible for otosclerosis have not been found, but foci on chromosomes 6, 7, and 15 have been implicated.

Achondroplasia

Achondroplasia may be associated with mixed hearing loss.

Paget disease

Paget disease may result in progressive, adult-onset conductive hearing loss, genetic sensorineural hearing loss (SNHL), or both. Other common findings of this bone disorder are enlargement of the skull, kyphosis, and shortening of stature. The hearing loss is thought to be due to a cochlear process. Genetic and environmental factors are likely to be contributing factors.

Syndromic hearing impairment, autosomal recessive

Usher syndrome

Usher syndrome is the most common cause of autosomal recessive syndromic SNHL.[18] Usher syndrome results in both hearing and visual impairments, and it is the etiology in at least 50% of persons with deafness and blindness. It may represent 3-6% of children born deaf and an additional 3-6% of children with milder hearing loss. The incidence is 4 in 100,000 births. Three main types of Usher syndrome are described, as follows:

• Type I is characterized by congenital severe-profound hearing loss and vestibular dysfunction. Retinitis pigmentosa (RP) develops in childhood and progresses from night blindness and loss of peripheral vision to blindness, through progressive degeneration of the retina. Vestibular dysfunction results in delayed motor milestones and may not walk until after 18 months.[22]

• Type II Usher syndrome is characterized by congenital mild-to-severe SNHL but normal vestibular function. Associate RP develops during the later teen years and tends to progress slower than in type I.

• Children with type III Usher syndrome have normal hearing at birth that progressively declines during the teen years, requiring hearing aids by adulthood. Vestibular function is usually fairly normal but may decline over time. RP begins at puberty and progresses into adulthood.

Early diagnosis is important in Usher syndrome and will impact management. Patients with type I Usher syndrome who rely on manual communication may be more significantly impacted with development of visual impairment, at which time auditory rehabilitation will be less complete than if initiated earlier. Electroretinogram can be performed after the age of 2 years and may aid in identifying retinal problems earlier than funduscopic examination and visual field tests. Genetic testing is now available and should be considered. Early identification and early cochlear implantation may mitigate the effect of dual sensory impairment if auditory-oral skills are developed prior to the onset of visual impairment.[23]

Twelve loci have been found to cause Usher syndrome. Genes and the proteins that they encode have been identified for 7 of the 12 loci. The genes that cause Usher syndrome are MY07A, USH1C, CDH23, PCDH15, and SANS, which cause type I Usher syndrome; USH2A,which causes type II Usher syndrome; and USH3A,which causes type III Usher syndrome. A mutation, named R245X, of the PCDH15 gene may account for a large percentage of type I Usher syndrome cases in today's Ashkenazi Jewish population.

Research indicates that massively parallel DNA sequencing may be an effective method of diagnosing pathogenic variants in Usher syndrome that is faster and less costly than more conventional genetic tests. In a study by Besnard et al involving patients with Usher syndrome or other forms of genetic deafness who had already been screened with Sanger sequencing, massively parallel targeted sequencing identified 98% of the variants that had been found in the previous screen.[24, 25]

A study by Shu et al reported that targeted exome sequencing quickly and accurately recognized genetic defects (a homozygous frameshift mutation and two compound heterozygous mutations) in two Chinese families affected by Usher syndrome.[26]

Pendred syndrome

Pendred syndrome is the second most common type of AR syndromic hearing loss. It is characterized by congenital severe-to-profound sensorineural hearing impairment and euthyroid goiter. Goiter develops in early puberty or adulthood. Affected individuals have an abnormal perchlorate test indicating delayed organification of iodine by the thyroid. Mondini dysplasia and dilated vestibular aqueduct are commonly found during radiographic evaluation. Mutations in SLC26A4, which codes for pendrin, have been identified. Genetic testing is available and can be suggested if a Mondini malformation is found during evaluation.

A study by Soh et al indicated that an association exists between SLC26A4 genotype and thyroid phenotype in Pendred syndrome, with patients who were monoallelic for the gene having normal perchlorate discharge and those with c.626G>T or c.3-2A>G having a lower median discharge (9.3%) than patients with other mutations (40%).[27]

Jervell and Lange-Nielsen syndrome

Jervell and Lange-Nielsen syndrome results in congenital genetic sensorineural hearing loss (SNHL) and a prolonged QT interval. Affected individuals have syncopal episodes and may have sudden death. High-risk children (ie, those with a family history that is positive for sudden death, SIDS, syncopal episodes, or long QT syndrome) should have a thorough cardiac evaluation. EKG is commonly included in screening protocols for congenital hearing loss.

Mutations in the KCNE1 and KCNQ1 genes cause Jervell and Lange-Nielsen syndrome. About 90% of cases of Jervell and Lange-Nielsen syndrome are caused by mutations in the KCNQ1 gene; KCNE1 mutations are responsible for the remaining 10% of cases.

These genes are responsible for coding potassium channel proteins critical for maintaining the normal functions of the inner ear and cardiac muscle. Mutations in these genes alter the usual structure and function of potassium channels or prevent the assembly of normal channels. These changes disrupt the flow of potassium ions in the inner ear and in cardiac muscle, leading to the hearing loss and irregular heart rhythm characteristic of Jervell and Lange-Nielsen syndrome.

Refsum disease

Refsum disease is a rare condition manifested by severe progressive genetic sensorineural hearing loss (SNHL) and retinitis pigmentosa due to abnormal phytanic acid metabolism. Because it can be treated with dietary modification and plasmapheresis, identification may be helpful

X-linked syndromic hearing loss

Alport syndrome

Alport syndrome is a result of mutations in type IV collagen genes that result in faulty basement membranes of the kidney and cochlea. The incidence is thought to be 1 in 5000 persons and is more common in males. The HL is bilateral and slowly progressive often starting in late childhood in the high frequencies. Deafness is common by age 25 years. In males, proteinuria progresses to end-stage renal disease before age 40 years.[28]

In females, end-stage renal disease is less frequent until later decades. Diagnostic criteria include family history of hematuria progressing to end-stage renal disease, progressive high frequency genetic sensorineural hearing loss (SNHL), thickening of the renal basement membrane by electron microscopy, and anterior lenticonus and perimacular flecks.

In 80% of patients with Alport syndrome, the inheritance is X-linked dominant. Patients with Alport syndrome have mutations in COL4A3, COL4A4, or COL4A5 near Xq22. Other forms are autosomal dominant or recessive and, in these cases, the severity is equal between the sexes.

Nonsyndromic genetic sensorineural hearing loss

An estimated 70-80% of hereditary hearing loss is nonsyndromic. Approximately 75% of nonsyndromic genetic sensorineural hearing loss (SNHL) is autosomal recessive, 15-20% is autosomal dominant, and 1-3% is X-linked. As highlighted by Van Laer et al, some genes may be associated with both autosomal dominant and recessive hearing loss. Some variability may be seen in the phenotype, based on the location and type of mutation of a gene and effects of modifying genes and environmental factors.[29]

When a gene locus for hearing loss is identified, it is named for the inheritance pattern and a consecutive number. DFNA indicates autosomal dominant gene loci, DFNB indicates autosomal recessive loci, and DFN indicates X-linked loci.[30] Mitochondrial disorders also exist. New gene loci are discovered every year.

Autosomal recessive nonsyndromic hearing loss is usually prelingual, nonprogressive, and severe to profound. Mutations in the connexin 26 gene at locus DFNB1 on chromosome 13 are thought to account for about 50% of recessive nonsyndromic hearing loss. 35delG is the most common mutation, but at least 90 different GJB2 mutations have been described.[31]

The gene GJB2 codes for connexin 26, a gap junction beta2 protein. These proteins form intercellular channels in the plasma membrane and facilitate the exchange of molecules between cells. Connexin 26 is expressed in the stria vascularis, spiral ligament, spiral limbus, and in supporting cells of the cochlea. It appears to have a role in recycling of potassium. The hearing loss is usually prelingual and varies from mild to profound. It is usually predominantly high frequency and sloping but may also present with a flat audiometric curve. It is most often bilateral and symmetric, but unilateral cases have been identified. The ear is usually radiologically normal. Connexin 26-related hearing loss can be inherited by autosomal recessive or dominant patterns.

Autosomal dominant nonsyndromic hearing loss is more likely to be postlingual than autosomal recessive nonsyndromic hearing loss and is more variable in frequency distribution and severity. A common X-linked nonsyndromic mutation at gene locus DFN3 causes a mixed hearing loss. These patients are prone to perilymph gushers during stapedectomy that will result in profound postoperative SNHL. The related gene is POU3F4.

An interesting mitochondrial gene mutation is that for aminoglycoside-induced genetic sensorineural hearing loss (SNHL). The mutation A1555G in the 12s rRNA gene makes a person susceptible to hearing loss after treatment with gentamicin, neomycin, or other aminoglycosides.

Several websites are devoted to cataloging gene mutations, including The Hereditary Hearing Loss Homepage and those of the Harvard Medical School Center for Hereditary Deafness and GeneTests.

Routine series of laboratory tests are not recommended in the evaluation of a hearing impaired patient. Rational assessment of the cost-benefit ratio and the clinician's index of suspicion should guide the selection of laboratory studies for an individual patient. Studies may include those listed below.

• Molecular genetic testing.[2] Assays are available for the following:

  • GJB2 (connexin 26)

  • Mitochondrial gene mutations in the 12SrRNA and tRNAser(UCN) genes (aminoglycoside-sensitive SNHL)

  • OTOF (associated with auditory neuropathy in some patients and nonsyndromic hearing loss in other patients)

  • GJB6 gene (connexin 30)

  • SLC26A4 (Pendred syndrome)

  • CDH23 (cadherin) and MYO7A (myosin), which account for approximately 70% of the mutations that cause Usher syndrome type I

  • COCH (associated with adult-onset dominant SNHL).

  • Genetic testing is available for a number of other genes, but the infrequency of most of them makes routine clinical testing impractical.

• Complete blood count (CBC) with differential

• Chemistries

• Blood sugar determination

• BUN and creatinine measurement

• Thyroid studies

• Urinalysis

• Fluorescent treponemal antibody absorption (FTA-ABS) test

• Specific immunoglobulin M (IgM) assays for toxoplasmosis, rubella, CMV infection

• Herpes virus autoimmune panel

• Autoimmune profile

  • Test of erythrocyte sedimentation rate (ESR)

  • Antinuclear antibody (ANA) test

  • Rheumatoid factor (RF) test

  • Measurement of complement levels

  • Raja-cell studies

  • Western blot (to identify serum anti-68 kd autoantibody)

  • Tests for circulating immune complexes

See the list below:

• CT scanning offers high-resolution images with 1-mm sections, which permit good visualization of the anatomy of the bones, ossicles, and inner ear.

  • CT assists in the diagnosis of suspected labyrinthine anomalies, such as a large vestibular aqueduct or Mondini dysplasia. CT scanning is also useful for diagnosing suspected labyrinthine fistula or temporal bone fractures.

  • CT may help in identifying the relatively nondysplastic and presumably somewhat-hearing ear when auditory habilitation is being considered.

  • A common abnormality noted on CT is an enlarged vestibular aqueduct. It is typically defined as an anteroposterior diameter of more than 1.5 mm at the operculum, but some clinicians and authors use a definition broader than this. Hearing loss associated with enlarged vestibular aqueduct is usually bilateral and progressive, and it may be associated with vertigo. It has an associate with Pendred and Mondini malformations.

• MRI has high soft tissue contrast, which makes it ideal for evaluation of the inner ear, internal auditory canal, and cerebellopontine angle.

  • MRI with gadolinium enhancement is the criterion standard for evaluating potential retrocochlear pathology as a cause of hearing loss.

  • Highly T2-weighted images obtained with appropriate sagittal sections can depict aplasia of the cochlear nerve and subtle malformations of the inner ear.

See the list below:

• Auditory brainstem response (ABR): ABR is most clinically useful for assessment of infants and young children.

  • Principle areas of application include the evaluation and diagnosis of the peripheral auditory system and related pathology and determination of the neural integrity of the acoustic nerve and brainstem pathway.

  • ABR provides a valid estimate of auditory sensitivity based on the threshold of response.

• Audiometry: Valid and reliable techniques are presently available to provide information relevant to presence, degree, and nature of hearing impairment in children within the first 24 hours of life.

  • Visual response audiometry yields precise information regarding auditory sensitivity in infants as young as 6 months. Head-turning responses to sound are conditioned through visual reinforcement, and ultimately the response behavior is controlled.

  • Play audiometry is ideal for children aged 2-5 years and for older children who are mentally or developmentally delayed. Conventional audiometric techniques are combined with testing situations in which the child can respond appropriately to stimuli by participating in a form of play activity. Hearing levels can be assessed for both speech and pure tone stimuli.

  • Conventional audiometry is traditionally reserved for children aged 3-5 years and older. Techniques include pure tone and speech audiometry (to determine air and bone conduction thresholds) and speech recognition.

  • Immittance audiometry provides an objective, rapid, and accurate assessment of middle ear function in infants and children. Immittance audiometry consists of 2 primary techniques, tympanometry and measurement of acoustic-reflex thresholds.

    • Tympanometry reflects the compliance of the middle ear system as the eardrum is artificially altered with varying degrees of air pressure in the external auditory canal (EAC). A noncompliant middle ear is consistent with effusion, which is a typical presentation in the infant population.

    • The acoustic-reflex threshold measurement is defined as the lowest intensity level that elicits stapedial muscle contraction. The acoustic-reflex response typically is in the range of 85 dB for the midfrequency stimulus. Deviations in the acoustic-reflex response, including elevated or absent thresholds, are synonymous with middle ear dysfunction

• Otoacoustic emissions (OAEs): OAEs are samples of measurable acoustic energy generated by vibratory patterns in the normal cochlea and propagated into the EAC by way of the middle ear apparatus. Emissions provide an objective measure of auditory sensitivity, frequency analysis, and cochlear integrity.

  • The 2 primary categories of otoacoustic emissions are spontaneous OAEs (SOAEs) and evoked OAEs (EOAEs). EOAEs can be subdivided into transient and distortion product OAEs (DPOAEs) according to the stimulus characteristics used to elicit their response. Clinical application is limited in that SOAEs are recorded in only approximately half of the population.

  • Transient OAEs and DPOAEs can be recorded in nonpathologic ears that do not have hearing loss >20-30 dB regardless of sex or age. The absence of measurable EOAEs is strongly predictive of a decrease in peripheral hearing, particularly in the 2000- to 4000-Hz range, where EOAEs appear to be most sensitive to dysfunction of the outer hair cells.

• ECG: Consider ECG to detect cardiac conduction anomalies, especially in any child who has a family history of SIDS, syncope, cardiac dysrhythmia, or sudden death in a child.

Histologic examination of temporal bones of patients with genetic patterned hearing loss has shown a variety of patterns.

Macrostructural malformations include the following:

Michel dysplasia is characterized by complete failure of inner ear development, while the external and middle ears may be normal and functional. Complete unilateral or bilateral deafness may ensue. The diagnosis rests on postmortem histopathology because radiographic studies cannot differentiate between Michel dysplasia and labyrinthitis ossificans.

Mondini dysplasia is possibly due to arrested development of the cochlea in its embryonic stage at approximately the sixth week of gestation. Only the basal turn of the cochlea is developed, and the bony cochlea is restricted to 1.5 turns. Mondini dysplasia may manifest in early childhood or in adulthood, with hearing that ranges from complete loss to normal hearing. It is inherited in an autosomal dominant fashion.

Scheibe dysplasia is the most common form of congenital dysplasia of the inner ear and is also known as cochleosaccular dysplasia. The bony labyrinth, membranous utricle, and semicircular canals are fully formed, while pars inferior structures, namely the saccule and cochlear duct, are poorly differentiated. Scheibe dysplasia is often noted in congenital hearing losses with autosomal recessive inheritance.

Alexander aplasia is characterized by aplasia of the cochlear duct. The organ of Corti, particularly the basal turn of the cochlea and adjacent ganglion cells, is affected most prominently. Hearing loss is most notable with high frequencies, whereas low-frequency hearing is relatively preserved.

On a microstructural basis, the study of the histopathology of temporal bones from patients with genetic hearing loss has demonstrated a wide variety of abnormalities including: partial or complete hair cell loss, reduced number of or atrophy of nerve cells and fibers, loss of supporting cells, degeneration of the tectorial membrane, atrophic, absent or degenerated stria vascularis, or even complete loss of the organ of corti and other cochlear structures.[32]

See the list below:

• Treat any middle ear disease, including otitis media, with appropriate medical therapy.

• Hearing amplification, whether with conventional or advanced technologic devices, is critical to the habilitation process. The goal of amplification is to take advantage of any residual hearing the patient may possess. At a minimum, the goal is to orient the patient to an acoustic event in his or her environment. Hearing amplification can usually be implemented with success by the age of 6 weeks.

• Assistive listening devices and personal systems may be helpful.

  • Personal devices aid in reducing the signal-to-noise ratio in various listening situations, such as watching television, in classrooms, and in auditoriums.

  • Telephone devices include volume controls and couplers for use with certain hearing aids. For individuals unable to use standard telephone devices, telecommunication devices for the deaf are available.

  • Captioning allows individuals with severe hearing impaired to watch television.

  • Signaling devices, which substitute visual signals for auditory signals, are available to detect environmental household sounds such as the doorbell, ringing telephone, alarm from an alarm clock, fire alarm, or a baby's cry.

Surgical management of external and middle ear deformities may be recommended in bilateral cases.

Cochlear implantation

Consider cochlear implantation for patients who do not demonstrate significant benefit from conventional hearing amplification. Cochlear implants are electronic devices designed to convert mechanical sound energy into electric signals that can be delivered to the cochlear nerve.

Perform a CT or MRI scan of the temporal bones prior to cochlear implantation to ensure the presence of an intact cochlea and cochlear nerve.

In children, substantially better performance is obtained when auditory input is restored with cochlear implantation in children younger than 2 years.

A study by Alzhrani et al indicated that in children with hearing loss due to a genetic syndrome, cochlear implantation leads to similar results with regard to auditory perception and speech intelligibility as it does in children with nonsyndromic hearing loss.[33]

Participation of many members of the medical community is required to offer comprehensive service to the family of a person with hearing loss. Pediatricians, audiologists, speech-language pathologists, educational specialists, and otolaryngologists must contribute to these efforts.

• Obtain an otolaryngology consult when hearing loss is suspected or diagnosed. The otolaryngologist identifies the hearing loss, assesses the cause, identifies risk factors, and obtains appropriate medical tests.

• A geneticist may offer assistance in establishing the etiology of SNHL. The geneticist can also provide genetic counseling to address a family's questions about the etiology of the patient's hearing loss and the risk of hearing loss in future children. Arnos has evaluated the ethical and social implications of genetic testing.[34]

• The audiologist is responsible for selection of the appropriate aid, which is a critical decision. Once hearing amplification is in place, systematic monitoring is necessary to ensure proper function of the device while monitoring speech and language development.

• A speech and language pathologist can provide appropriate educational programs necessary to enrich social, emotional, and academic development. The patient's linguistic and communicative skills must be analyzed with the understanding that the final indication of the success of the habilitative program is the patient's language capability and not the level of hearing. As a general rule, initially present language to children who are hearing impaired using all available inputs, including auditory, visual, and tactile stimuli.

• An ophthalmology evaluation is important to assess visual acuity and to evaluate any possible ocular components of syndromic hearing loss.

Anecdotal reports associate increased risk of hearing loss with patients who have enlarged vestibular aqueducts and participate in contact sports.

See the list below:

• Otologist

  • Encourage follow-up annually and as needed.

  • Frequent findings include problems with the hearing aid, disease of the external or middle ear, and progressive hearing loss.

  • Follow-up must also reassess the accuracy of the initial diagnosis with appropriate modifications made to the habilitative plan.

• Audiologist

  • After a device hearing amplification is in place, systematic monitoring is necessary to ensure proper function of the device while monitoring speech and language development.

  • Schedule audiologic reevaluation every 3 months during the first year and then every 6 months thereafter.

  • Calibrate hearing aids periodically and fit new molds when necessary.

  • Periodic audiometric testing is necessary to rule out fluctuation or progression of hearing loss.

• Speech and language pathologist

  • Speech and language therapy is imperative to promote proper language and communication skills.

  • A plan for systematic monitoring is required to ensure that a child with hearing impairment develops the necessary speech and communication skills to meet his or her daily communication needs.

The patient must avoid ototoxic medications and loud noise exposure in the absence of hearing protection.

Children with unilateral hearing loss have difficulty with sound localization and with hearing in settings with background noise that can make school life difficult. Among such children, the incidence of school-grade failure, distractibility, daydreaming, inability to follow directions, and behavioral problems increases.

Children with profound bilateral hearing loss have reductions in receptive and expressive language skills, rates of graduation from high school, reading levels, and math skills. Deaf individuals may have low rates of employment, few opportunities for financial gain, restricted socialization, language barriers that resulting in limited social groups and reduced quality of life.

Using the Peabody Picture Vocabulary Test, Fourth Edition (PPVT-4), a Danish study, by Mey et al, indicated that children with either Pendred syndrome or nonsyndromic enlarged vestibular aqueduct (NSEVA) have lower receptive language capabilities than do children with normal hearing, as well as children with congenital and hereditary nonsyndromic hearing impairment (mixed group). The investigators also found that children in the mixed hearing impairment group underwent cochlear implant surgery at an earlier median age than did the patients with Pendred syndrome/NSEVCA (age 11 mo vs age 43 mo, respectively).[35]

With proper amplification, speech and language therapy, and an educational program, a patient with SNHL may participate in mainstream society, obtain gainful employment, and be competent in adult life. Children with profound deafness that is rehabilitated with cochlear implants achieve language development on par with that of their peers.

See the list below:

• When counseling the parents of a child who is hearing impaired, one must address the probability of having subsequent affected children. This risk depends on the status of the parents and on the number of affected offspring.

• For excellent patient education resources, visit eMedicineHealth's Ear, Nose, and Throat Center. Also, see eMedicineHealth's patient education article Hearing Loss.

• The website www.babyhearing.org is designed to help parents understand hearing loss identification and treatment.

• The American Academy of Otolaryngology-Head and Neck surgery provides several fact sheets with information on hearing loss and related ear issues at http://entlink.net/HealthInformation/Genes-and-Hearing-Loss.cfm.

• Many resources exist for education, rehabilitation, and advocacy for persons with hearing impairment, including www.agbell.org, www.listen-up.org, http://entlink.net/healthinformation/ears, and www.asha.org.