Syndromic Sensorineural Hearing Loss

The auditory system is highly complex, and disruptions at the level of the middle ear, cochlea, and central nervous system can result in variable degrees of hearing loss. Hearing also depends on precise biochemical, metabolic, vascular, hematologic, and endocrine function. Disruption in any of these systems can profoundly affect the auditory system. The pathophysiology differs with each type of syndromic hearing loss. This article attempts to describe the basic pathophysiology of each syndrome, as it is currently understood. However, the molecular structure and pathways of the hearing system is largely undiscovered. It is interesting to note that the study of the genetic basis of hearing loss continues to enhance the understanding of the molecular basis of normal hearing.[1]

Frequency

United States

About 21 million persons are hearing impaired, and approximately 1% of those persons are profoundly hearing impaired. Approximately 4000 hearing-impaired infants are born each year. The average incidence of hearing loss in neonates in the United States is 1.1 per 1000, with variability among states ranging between 0.22 and 3.61, according to Mehra et al.[2] In this study, the prevalence of childhood and adolescent hearing loss was 3.1%, with higher rates in Hispanic Americans and in families with lower incomes.[2]

Filtering out the prevalence of syndromic hearing loss among nonsyndromic and nonhereditary hearing loss is a difficult and imperfect task, given phenotypic variability, complicating medical risk factors, and incomplete family histories. After reviewing 780 abstracts and summarizing 43 studies published in English between 1966 and 2002, Morzaria et al reported that the most common etiologies of hearing loss in children were unknown (37.7%) and genetic nonsyndromic (29.2%), while genetic syndromic hearing loss accounted for 3.2% of the etiologies.[3]

A study by Mehta et al of 660 patients with hearing loss evaluated at the Genetics of Hearing Loss Clinic at The Children’s Hospital of Philadelphia found syndromic causes in 7% of the cohort; Usher and Waardenburg syndrome were the most common etiologies in this subgroup.[4]

International

Hearing impairment affects up to 30% of the international community, and estimates indicate that 70 million persons are deaf. Proportions of hereditary verses acquired and syndromic versus nonsyndromic hearing losses 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, since 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.[5]

Ancestry and race play a large role in the prevalence of syndromic hearing loss and may influence the prevalence of nonsyndromic and acquired hearing losses. Saunders et al studied a rural community in Nicaragua and demonstrated a prevalence of significant hearing loss of 18% in a group of school-aged children in which 24% of the children had an identifiable family history of hearing loss. In a clinic-based group of 96 patients with hearing loss, dysmorphic features were recognized in many of the children, including atresia, low-set or cup ear deformity, juvenile cataracts, malar hypoplasia, hemifacial microsomia, micrognathia, and branchial cleft cysts. Five children had features that suggested a defined syndrome (neurofibromatosis, Goldenhar, branchiootorenal syndrome, Poland syndrome, and Down syndrome), but many others had significant dysmorphisms that were thought to be either unrelated to hearing loss or could not be diagnosed as a defined syndrome.[5]

Additionally and ideally, large-scale epidemiologic studies are needed and will become more informative as molecular testing is made available to the world’s populations.

Mortality/Morbidity

The morbidity of hearing loss varies with the severity of involvement; however, it is a significant problem even for the most mildly involved. Patients with unilateral hearing loss have difficulty hearing in background sound and difficulty localizing sound. Bilateral profound hearing loss has a great potential for morbidity. Many studies support that deafness significantly affects quality of life. Social, educational, and earning potential are diminished.

In patients with syndromic hearing loss, morbidity and mortality is often more significant with anomalies of the other involved system or systems. For example, children with Jervell and Lange-Nielsen syndromes are at risk for syncope, arrhythmias, and sudden death. Children with Usher syndrome develop hearing loss, vestibular impairment, and visual impairment. Usher syndrome accounts for a large percentage of the etiology of deaf-blindness. The dual sensory impairment has huge implications for communication and education. Glomerulonephrosis associated with Alport syndrome can end in kidney failure and necessitate kidney transplant.

Age

Early identification of hearing loss and appropriate intervention provides the best opportunity for counseling, habilitation, and development. Additionally, early enrollment in services for a child with hearing impairment reduce health care, special education, and other service costs for families and taxpayers. Prior to the initiation of universal hearing screening for newborns, fewer than 50% of children who are hearing impaired were identified before age 3 years. Identification of risk factors (prematurity, low birth weight, low Apgar scores) detects less than 50% of infants who have or are at risk for hearing loss.

Currently, 36 states mandate hearing screening for newborns according to the National Newborn Screening and Genetic Resource Center, as of 3/11/2009. Screening is almost universally offered in the remaining states but not required by law. Currently, the average age at detection is about 14 months. However, in Virginia, where universal infant screening has been mandated by law since July 1, 2000, and became greater than 98% compliant by 2004, the average age at diagnosis decreased from 16.2 months to 4.5 months.

Children with syndromic features associated with hearing loss should be screened early and routinely for hearing loss.[6] Even if initial screening examinations indicate normal hearing, they remain at risk. During infancy and early childhood, parents should be aware of and questioned about the child's achievement of hearing and language milestones. Parental concerns should be taken seriously. If risks for hearing loss are high or the child does not seem to be meeting landmarks, a hearing evaluation should be performed. Some syndromes, such as Pendred, Alport, Refsum, neurofibromatosis type II, Usher, and osteopetrosis, may place the patient at risk for progressive hearing loss.

Sensorineural hearing loss (SNHL) is a common disorder that affects millions of people. Hearing loss has many different presentations, ranging in severity from mild to profound, including low- and high-pitch patterns, and can affect people of any age.

Genetic hearing loss may be present at birth (congenital) or may progress in either childhood or adulthood. About 50% of congenital hearing loss is genetic and about 50% is acquired. Genetic hearing loss may appear as an isolated finding or as part of a syndrome. About 70% of genetic hearing loss is nonsyndromic, and about 30% is syndromic.

The London Dysmorphology Database lists 396 syndromes that include hearing loss among the anomalies.[7] The most common and unique syndromes are discussed in this article. For a general discussion of genetic hearing loss, see Genetic Sensorineural Hearing Loss.

See the image below.

Inner ear.

Upon identification of hearing loss, a complete history should include gestational, perinatal, postnatal, and family histories. Medical problems or morphologic abnormalities of the ear, face, or other organ systems may, in association with hearing impairment, indicate a recognizable syndrome.

Because abnormalities of virtually every organ system have been associated with sensorineural hearing loss (SNHL), physicians must become familiar with the constellation of physical findings that may help determine the etiology of a patient's hearing impairment. The physical examination should incorporate an in-depth ears, nose, throat, head, and neck evaluation, along with an overall assessment of general physical and neurologic status.

Abnormalities of many systems have been associated with syndromic hearing loss, including the following:

• Craniofacial malformations

• Dental abnormalities

• Ocular abnormalities

• Renal defects

• Cardiac abnormalities

• Endocrine dysfunction

• Neurologic dysfunction

• Skeletal abnormalities

• Integumentary abnormalities

• Metabolic disease

• Chromosomal abnormalities

Clinical findings suggestive of syndromes associated with hearing loss include the following:

• Ear examination findings

  • Auricular deformity - Treacher-Collins syndrome, Goldenhar syndrome

  • External canal atresia or stenosis - Treacher-Collins syndrome, Goldenhar syndrome

  • Preauricular pits - Branchiootorenal syndrome

  • Preauricular skin tags - Goldenhar syndrome

  • Enlarged vestibular aqueduct - Pendred macrotia, Kabuki syndrome, Turner syndrome, Opitz-Frias syndrome

  • Lop ears - Trisomy 21, otopalatodigital syndrome

  • Cup ear - Pierre Robin sequence

  • Microtia - Treacher-Collins syndrome, Goldenhar syndrome, first branchial cleft syndrome, Möbius syndrome, Duane syndrome

• Eye examination findings

  • Cataracts - Congenital rubella

  • Coloboma - Coloboma of iris, heart deformities, choanal atresia, retarded growth, genital and ear deformities (CHARGE) association

  • Dystopia canthorum - Waardenburg syndrome (WS)

  • Heterochromia irides - WS

  • Keratitis - Cogan syndrome

  • Ocular palsy - Duane syndrome

  • Retinal atrophy - Cockayne syndrome

  • Retinitis pigmentosum - Usher syndrome

  • Retinal degeneration - Alström syndrome

  • Congenital blindness, pseudotumor retinae - Norrie syndrome

• Integumentary examination findings

  • Depigmentation - albinism, piebaldness, WS, Tietze syndrome

  • Ectodermal dysplasia - Ichthyosis

  • Hypopigmentation - Albinism

  • Lentigines - Lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, and deafness (LEOPARD) syndrome

  • White forelock - WS syndrome

• Cardiac findings

  • Widened electrocardiographic wave (QRS) or bundle branch block (BBB), pulmonary stenosis - LEOPARD syndrome

  • Prolonged QT - Jervell and Lange-Nielsen syndrome

  • Mitral Insufficiency - Forney syndrome

• Renal findings

  • Dysfunction - Alport syndrome, Hermann syndrome, Fanconi anemia, branchiootorenal syndrome

  • Malformation - Goldenhar syndrome

• Dental findings

  • Abnormal dentin - Osteogenesis imperfecta

  • Pegged (Hutchinson) incisors - Congenital syphilis

• Endocrine/metabolic findings

  • Goiter - Pendred syndrome

  • Hypogonadism - Alström syndrome

  • Obesity - Laurence-Moon-Biedl syndrome

  • Mucopolysaccharidosis - Hunter, Hurler, Sanfilippo, and Morquio syndromes

  • Diabetes mellitus - Alström, Hermann syndromes

  • Ovarian dysgenesis - Perrault syndrome

  • Thymus agenesis - DiGeorge syndrome

• Chromosomal abnormalities

  • Trisomy 13 - Patau syndrome

  • Trisomy 18 - Edwards syndrome

  • Trisomy 21 - Down syndrome

  • Trisomy 22

• Neurologic abnormalities

  • Ataxia - Spinocerebellar degeneration

  • Epilepsy - Herman syndrome

  • Peripheral neuropathy - Flynn-Aird syndrome

  • Polyneuropathy - Refsum disease

• Skeletal examination findings

  • Dwarfism - Achondroplasia, Cockayne syndrome

  • Fusion of cervical vertebrae - Klippel-Feil syndrome

  • Limb deformities - Osteogenesis imperfecta, Hurler syndrome

  • Scoliosis, elongated limbs - Marfan syndrome

  • Syndactyly - Apert syndrome

• Craniofacial abnormalities[8]

  • Acrocephaly (tower skull) - Apert syndrome

  • Branchial fistulas - Branchiootorenal syndrome

  • Cleft palate, small mandible - Pierre Robin sequence

  • Cranial synostosis - Crouzon syndrome

  • Malar/facial bone anomalies - Treacher-Collins syndrome

  • Midface hypoplasia - Crouzon syndrome

  • Ocular/auricular anomalies - Goldenhar syndrome

Autosomal dominant syndromic hearing loss

These are less frequent causes of hearing loss than autosomal recessive disorders. Examples include Waardenburg, neurofibromatosis, Tietze, Hermann, Leopard, Kearns-Sayre, Crouzon, Forney, achondroplasia, Duane, Marfan, and branchiootorenal syndromes.

• Waardenburg syndrome[9]

  • Waardenburg syndrome (WS) is the most common cause of autosomal dominant syndromic hearing loss. It occurs in approximately 2 per 100,000 births and is estimated to account for 2% of all cases of congenital hearing loss in the United States. A literature review by Song et al found hearing loss in 71% of patients with WS, with such loss being primarily bilateral and sensorineural.[10]

  • WS is characterized by autosomal dominant inheritance with variable penetrance. WS has undergone intense gene mapping and has been localized at gene locus 2q35 or 2q37.3. Mutations in PAX3 cause WS type I and WS type III. Some cases of WS type II are caused by mutations in MITF. WS type IV has been linked to mutations in EDNRB, EDN3, and SOX10.

  • Temporal bone pathology includes atrophy of the organ of Corti and stria vascularis, with reduction in the number of spiral ganglion nerve cells. Hearing loss can be unilateral or bilateral, with severity that ranges from total loss to moderate loss with preservation of high frequencies.

  • Type I WS includes the following primary features:

    • Lateral displacement of the medial canthi and lacrimal puncta (100%)

    • Hyperplastic high nasal root (75%)

    • Hyperplasia of the medial portion of the eyebrows (50%)

    • Partial or total heterochromia irides (25%)

    • Circumscribed albinism of the frontal head hair or white forelock (20%)

    • Sensorineural deafness, unilateral or bilateral (25%)

  • Type II WS is differentiated by the absence of dystopia canthorum and a higher incidence of SNHL, up to 55%. Estimates indicate type II as 20 times more frequent than type I.

  • Type III WS includes upper-limb malformations.

  • Type IV WS includes Hirschsprung disease

• Branchiootorenal syndrome is the second most common type of autosomal dominant syndromic hearing loss. Branchial fistulas, renal anomalies, and anomalous development of the external, middle, and inner ear typify this disorder. Inheritance is via autosomal dominant transmission. Hearing loss may be conductive, sensorineural, or mixed and is characterized by preauricular pits and auricular malformations of the outer ear and by structural defects of the middle ear and inner ear. Mutations in the EYA1, SIX1 and SIX5 genes have been identified.

• Neurofibromatosis 2 is caused by a mutation in the NF2 gene on chromosome 22 and is characterized by the development of multiple tumors, including vestibular schwannomas, meningiomas, gliomas, and ependymomas. In some cases, tumors may manifest as early as 8-12 years of age. Fortunately, the hearing loss associated with vestibular schwannomas is potentially treatable with early surgical intervention.

Autosomal recessive disorders

See the list below:

• Usher syndrome[9]

  • The reported incidence for Usher syndrome is approximately 3 per 100,000 live births. (A study by Yoshimura et al estimated that the prevalence of Usher syndrome in Japan is at least 0.4 per 100,000 population.[11] ) The disorder is responsible for up to 10% of cases of congenital deafness, and it is inherited in an autosomal recessive fashion. It is the most common type of autosomal recessive syndromic hearing loss. Usher syndrome features progressive blindness due to retinitis pigmentosa, along with moderate-to-severe SNHL, and accounts for about 50% of the deaf blind in the United States.

  • Vision impairment is not easily identified in the first decade of life. Funduscopic examination before age 10 years is limited. Electroretinography can reveal early retinal abnormalities in young children but is not routinely available. Night blindness and visual field deficits may mark developing retinitis pigmentosa. Loss of vision is progressive, and 50% of individuals develop complete blindness before age 50 years.

  • Hearing loss is generally present at birth, and 85% of affected individuals eventually become totally deaf. Histopathologic findings include degeneration of sensory epithelium within the cochlea. Absence of cochlear microphonic potentials indicates hair cell dysfunction as a cause for noted hearing impairment. Vestibulocerebellar ataxia is present in a high percentage of individuals with severe deafness.

  • The following 3 types of Usher syndrome are found:

    • Type I is characterized by bilateral congenital severe to profound hearing loss and poor vestibular function.

    • Type II is characterized by mild-to-moderate hearing loss at birth and normal vestibular function.

    • Type III Usher syndrome is characterized by progressive hearing loss and vestibular dysfunction.

  • The genetic basis of Usher’s syndrome is complex with mutations at 10 loci and 8 genes identified including MYO7A, USH2A, CDH23, PCDH15 and others.[12]

• Pendred syndrome is transmitted in an autosomal-recessive fashion and encompasses a clinical triad of congenital hearing loss, multinodular goiter, and pathologically decreased perchlorate test result.[9]

  • Goiter is not present at birth but rather develops in early puberty or adulthood and is due to abnormal organification of iodine. Pendred syndrome accounts for up to 5-10% of recessive hereditary hearing loss cases. Hearing loss is typically bilateral and most prominent in higher frequencies, often with positive recruitment suggestive of a cochlear site of lesion. A Mondini cochlear malformation and enlarged vestibular aqueduct are often identified.

  • Mutations in SLC26A4 are commonly identified. The SLC26A4 gene codes of pendrin, a protein that transports chorine, iodide and bicarbonate in and out of cells. The protein is important for the function of the inner ear and thyroid.[13] Genetic testing is available for mutations in this gene and is indicated in patients with Mondini malformation or enlarged vestibular aqueduct.

• Jervell and Lange-Nielsen syndrome is thought to be the third most common cause of autosomal syndromic hearing loss and accounts for 1% of all cases of recessive hearing loss. This disorder is characterized by electrocardiographic changes of a prolonged QT interval, Stokes-Adams attacks, congenital bilateral severe hearing loss, and sudden death. Syncopal attacks begin in early childhood, with sudden death often occurring in later years. Postmortem examinations have revealed abnormal cardiac defects, including degeneration of fibers of the sinoatrial node, fibrosis, hemorrhage, and infarction.

  • Temporal bone findings include atrophy of the organ of Corti and spiral ganglion, along with large periodic acid-Schiff (PAS)–positive hyaline deposits throughout the membranous labyrinth. Atrophy of sensory cells within the utricle and saccule is also evident.

  • A screening ECG may show prolonged QT interval, but the sensitivity is not high. Children with a family history of sudden death, sudden infant death syndrome (SIDS), syncopal episodes, or prolonged QT interval should be closely examined.

  • The genetic basis of Jervell and Lange-Nielsen syndrome is thought to be mutations in the KCNQ1, and less commonly, the KCNE1 gene, that are responsible for coding proteins that form potassium transport channels. These channels are critical in the function of the inner ear and heart muscle. The KCNE1 and KCNQ1 genes provide instructions for making proteins that work together to form a channel across cell membranes. These channels transport positively charged potassium atoms (ions) out of cells. The movement of potassium ions through these channels is critical for maintaining the normal functions of inner ear structures and cardiac muscle.[14]

• Cockayne described a syndrome of dwarfism with retinal atrophy and deafness. Classic onset occurs during the second year of life. Inheritance is in an autosomal-recessive pattern. Characteristics include dwarfism with kyphosis and ankylosis, prognathism, sunken eyes, mental retardation, retinal atrophy, thickened skull, carious teeth, and hearing loss. Hearing loss is bilateral, sensorineural, and progressive. Evidence points to degenerative changes of the spiral ganglion, cochlear nucleus, and olivary nucleus. According to the Genetics Home Reference, mutations in ERCC6 and CRCC8 cause Cockayne syndrome. These genes code for proteins that are involved in repairing damaged DNA. If damaged DNA accumulates, cell function is compromised and cell death occurs, likely contributing to growth failure and premature aging.[15]

• Alström syndrome is characterized by features such as retinitis pigmentosa, diabetes mellitus, cardiomyopathy, short stature, obesity, and progressive hearing loss. The disease can lead to liver failure, kidney failure and pulmonary problems, although the presentation is variable. Hearing loss, generally of the sensorineural variety, typically occurs by age 10 years. Inheritance is by autosomal recessive transmission. Mutations in ALMS1 are linked to Alström, but the function of the protein it codes is unknown.[16]  In a study of the histopathology of the inner ear in patients with Alström syndrome, Nadol et al reported an association between sensorineural hearing loss and degeneration of the organ of Corti’s inner and outer hair cells and of the spiral ganglion cells, as well as atrophy of the stria vascularis and spiral ligament; the report was based on two genetically confirmed cases.[17]

• Refsum disease is a recessive-inherited disorder characterized by retinitis pigmentosa, ichthyosis, polyneuritis, cerebellar ataxia, and hearing loss. Affected individuals often survive through the second decade of life. Visual loss typically occurs in patients older than 20 years. Progressive SNHL occurs in more than 50% of patients. Degeneration of the organ of Corti and stria vascularis have been reported in histopathologic studies.

• Disorders with X-linked, variable, or unknown inheritance have been identified.

Disorders with X-linked, variable, or unknown inheritance

See the list below:

• Alport syndrome represents the most common form of hereditary nephritis, with an incidence of 1 case per 200,000 individuals. Hematuria, posterior cataracts, corneal dystrophy, and dislocation of the lens characterize the condition. Although the disease is more common in females, boys are affected more severely than girls, commonly progressing to end-stage renal failure during their second or third decade of life. Untreated males die by age 30 years. Symptoms typically appear during the first decade of life.

  • Hearing loss is usually bilateral and symmetric, but progressive SNHL, with higher frequencies most prominently affected, has also been noted. Autosomal dominant, autosomal recessive and X-linked forms have been identified. X-linked inheritance is thought to cause about 85% of cases. Mutations in the COL4A3, COL4A4, and COL4A5 genes have been linked to Alport syndrome.

  • These genes code for Type IV collagen, a protein important in the structure and function of the basement membrane of the glomerular membrane and basilar membrane of the stria vascularis. In the glomerulus, the basement membrane eventually fails and leads to end-stage renal disease. The pathophysiologic mechanisms of hearing loss are unknown but Merchant et al identified separation of the basilar membrane and the basement membrane and cellular dysmorphology within the organ of corti.[18]

• Norrie Disease is a rare disorder caused by a mutation in the NDP gene located on the X chromosome that codes for a large protein, designated norrin, the seems to play a role in signaling developmental activities, including cell division, adhesion, and migration. As a result, problems may include vision impairment, motor developmental delay, retardation, and hearing loss.[19]

• Lysosomal storage diseases: Inborn errors of metabolism, including mucopolysaccharidoses (Hurler syndrome, Hunter syndrome) and sphingolipidoses (Fabry disease), often manifest with SNHL as part of the clinical presentation.

  • Hurler syndrome, inherited as an autosomal recessive trait, is a lysosomal storage disease caused by an enzymatic deficiency that results in accumulation of the mucopolysaccharides heparin sulfate and dermatan sulfate. Hurler syndrome is characterized by mental retardation, dwarfism, kyphosis, hepatosplenomegaly, and hearing loss. Hearing loss is generally mixed with prominence of sensory loss in the higher frequencies. Temporal bone studies have demonstrated PAS-positive material within the substance of the mesenchyme with degeneration of the organ of Corti. Generally, survival is rare past the 14th year of life. Hunter syndrome, inherited as an X-linked trait, is similar to Hurler syndrome in its clinical presentation.

  • Hunter syndrome is a milder form, with those enduring the condition commonly surviving into the early third decade of life. Hearing loss may be conductive, sensorineural, or mixed.

  • Fabry disease is also inherited in an X-linked fashion, leading to accumulation of sphingolipid within endothelial, smooth muscle, and ganglion cells. Hearing loss is typically bilateral with a predominant sensorineural high-frequency loss. Histopathologic studies of affected temporal bones include atrophy of the spiral ligament and accumulation of sphingolipid in vascular endothelial and ganglion cells of the auditory system.

• Trisomy 13 occurs in 1 per 6000 births. Congenital malformations are so severe that most affected infants do not survive beyond their first year of life. Clinical features include microcephaly, cleft lip and palate, polydactyly, rocker-bottom feet, low-set malformed pinna, cardiac dextroposition, scalp defects, and mental retardation. Temporal bone analysis reveals cystic changes within the stria vascularis, shortened length of the cochlea, saccular degeneration, and anomalies of the semicircular canals.

• Trisomy 18 reportedly occurs in 1 per 10,000 live births, although some reports place the incidence as high as 1 per 5,000 live births. Most affected infants do not survive past their third month of life, although up to 13% live past age 1 year. Clinical features include malformed pinna, micrognathia, prominent occiput, intestinal defects, and mental retardation. Temporal bone histopathology demonstrates incomplete development of the stria vascularis, semicircular canal anomalies, and decreased spiral ganglion cells.

• Trisomy 21, or Down syndrome, is the most common chromosomal disorder in the world. Incidence of Down syndrome is 1 per 1000 births overall, with an increasing incidence based on maternal age (1 per 25 births in women > 45 y). Clinical features include a broad short trunk, epicanthal folds, muscular hypotonia, congenital heart disease, and mental retardation. Hearing loss occurs in up to 78% of cases, with conductive, sensorineural, and mixed losses evident. Histopathologic temporal bone findings include residual mesenchyme in the middle ear, endolymphatic hydrops, and a wide angle of the facial nerve genu.

• Klippel-Feil syndrome was described in 1912. This syndrome is characterized by congenital fusion of 2 or more cervical vertebrae, high scapula, spina bifida, facial asymmetry, spasticity, and congenital heart defects. When associated with bilateral abducens palsy and hearing loss, it is referred to as Wildervanck syndrome. Hearing loss is of the profound sensorineural type, but conductive and mixed losses have also been reported. Hypoplasia of the inner ear, with both bony and membranous labyrinth underdevelopment, has been reported. Inheritance pattern is heterogeneous.

• Wildervanck syndrome (cervico-oculo-acoustic dysplasia) includes fusion of cervical vertebrae, short neck, low hairline posteriorly (Klippel-Feil) plus enophthalmos, mixed hearing loss, and lateral gaze weakness. A female predominance for Wildervanck syndrome is found. Inheritance is X-linked dominant.

• Albinism is due to defects in the biosynthesis and distribution of melanin. Oculocutaneous albinism is an autosomal recessive disorder; patients demonstrate lack of pigmentation in the skin, eyes, and hair. Most cases associated with SNHL are of the oculocutaneous form with hearing loss that varies in degree of severity.

• Otopalatodigital syndrome is thought to be X-linked recessive and includes cleft palate, fishmouth, clinodactyly, prominent forehead, hypertelorism, and antimongoloid palpebral fissures. Hearing loss is conductive because of ossicular malformations.

• X-linked disorders associated with syndromic hearing loss include Kearns-Sayre syndrome, myoclonic epilepsy and ragged red fibers, mitochondrial encephalopathy, lactic acidosis, and strokelike episodes, and maternally inherited diabetes and deafness.

See the list below:

• A routine series of laboratory tests is not recommended in the evaluation of patients with hearing impairment. A rational assessment of the cost-benefit ratio and the clinician's index of suspicion dictate the selection of necessary laboratory studies to be performed for each individual patient.

• Studies may include the following:

  • Genetic testing, including connexin 26 gene mutation testing. (Patients with syndromic features benefit from a genetic evaluation. Clinical testing for many genes associated with hearing loss is available.)

  • CBC count with differential

  • Chemistries

  • Blood sugar

  • BUN/creatinine

  • Thyroid function studies

  • Urinalysis

  • Fluorescent treponemal antibody absorption (FTA-ABS)

  • Specific immunoglobulin M (IgM) assays for toxoplasmosis, rubella, cytomegalovirus, herpes virus, and autoimmune panel, eg, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), rheumatoid factor (RF), complement levels, Raja cell studies, Western blot to identify a serum anti-68 KD autoantibody, and circulating immune complexes

See the list below:

• Computed tomography (CT) scanning

  • CT scanning offers very high-resolution images with 1-mm slices, allowing good visualization of the anatomy of the bones, ossicles, and inner ear.

  • CT scanning may be used to identify potentially surgically reparable causes of SNHL and may also be used to identify the less dysplastic, and presumably better hearing ear when considering auditory habilitation. CT abnormalities are found in up to 30% of individuals with hearing loss and thus are an important component of the evaluation. For example, enlarged vestibular aqueduct and Mondini malformation are common findings in Pendred syndrome.

• Magnetic resonance imaging (MRI): High soft tissue contrast makes MRI ideal for evaluation of the inner ear, internal auditory canal, and cerebellopontine angle.

• Renal ultrasonography: Consider renal ultrasonography when abnormalities are suspected.

See the list below:

• Valid and reliable techniques are available to determine the presence, degree, and nature of hearing impairment in children as early as the first 24 hours of life. Such techniques include the following:

  • Auditory brainstem response

  • Audiometry

  • Tympanometry

  • Acoustic reflex threshold measurement

  • Otoacoustic emissions (OAE)

• Electrocardiography: Consider ECG as a means to reveal cardiac conduction anomalies when an appropriate degree of clinical suspicion is present.

• Electrooculography can identify retinitis pigmentosa earlier than a physical examination.

See the list below:

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

• Amplification

  • The goal of amplification is to use any residual hearing to at least orient patients to surrounding environments. Hearing amplification can generally be implemented successfully during the first 6 weeks of life.

  • Available hearing amplification devices include conventional analog hearing aids, digital hearing aids, bone conduction hearing aids, and bone-anchored hearing aids. Other middle and inner ear implantable devices are undergoing clinical trials.

• Assistive listening devices and personal systems

  • Personal devices, such as FM trainers, aid in reducing the signal-to-noise ratio in various listening situations with significant background noise, eg, classrooms.

  • Telephone devices can include such items as volume controls and couplers for use with certain hearing aids, along with telecommunication devices for deaf persons who are unable to use standard telephones.

  • Closed captioning allows television use for individuals who are severely hearing impaired.

  • Signaling devices substitute visual signals for auditory signals. They can detect environmental sounds, such as doorbells, telephones, alarm clocks, fire alarms, or crying babies.

Surgical management of external and middle ear deformities can be recommended for bilateral hearing loss and some unilateral cases.

Cochlear implantation

Cochlear implants are electronic devices designed to convert mechanical sound energy into electric signals that can be delivered to the cochlear nerve. Consider cochlear implantation for patients who do not significantly benefit from conventional hearing amplification.[20, 21, 22]

To preoperatively ensure the presence of an intact cochlear nerve, consider MRI. CT scanning of the temporal bones is routinely performed to identify cochlear abnormalities.

Children younger than 5 years who have restored auditory input via cochlear implantation achieve substantially better language skills. Cochlear implantation may be performed at age 1 year.

A study by Alzhrani et al found that the results of cochlear implantation in children with hearing loss due to a genetic syndrome (Waardenburg, Usher, or Dandy-Walker syndrome or albinism) approximated those in children with nonsyndromic hearing loss. The investigators reported that postimplantation auditory perception and speech intelligibility levels were similar in both study groups, as was the final pure-tone average.[23]

A literature review by Davies et al indicates that cochlear implants can benefit most patients with Usher syndrome. The studies reviewed offered agreement that at any age, cochlear implantation for Usher syndrome results in better outcomes with regard to pure-tone audiometry, speech production, and quality of life. However, with Usher syndrome type I, according to the investigators, patients are best served by bilateral cochlear implantation performed at the earliest feasible age.[24]

See the list below:

• Geneticist

  • Geneticists may offer assistance in establishing the etiology of SNHL.

  • Geneticists also provide genetic counseling to address a family's questions about the etiology of the patient's hearing loss and the risk of recurrence for future children.

• Audiologist

  • Audiologists assist in selecting the most appropriate hearing aid for the patient. Selection of the appropriate aid is critical and is usually the responsibility of the audiologist.

  • Systematic monitoring is necessary to ensure proper function of the device while monitoring speech and language development.

• Speech and language pathologist

  • Patients' linguistic and communicative skills must be analyzed while understanding that language capability, and not the hearing level, is the final indication of a successful habilitative program.

  • Normally, language should first be presented to children who are hearing impaired through all available inputs, including auditory, visual, and tactile stimuli.

• Ophthalmologist: Consider consultation to assess visual acuity and to evaluate any possible ocular components of syndromic hearing loss.

See the list below:

• Otologist

  • Patients should see an otologist on an annual and as-needed basis. Systematic otologic and audiologic follow-up leads to significant findings in up to 58% of children.

  • Frequent findings include problems with hearing aids, diseases of the external or middle ear, and progressive hearing losses.

• Audiologist

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

  • Hearing aids should be calibrated periodically and new molds fitted 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.

  • Follow-up must also reassess the accuracy of the initial diagnosis, and appropriate modifications to the habilitative plan must be implemented. Assessment of effectiveness of the educational program is critical to follow-up evaluations.

Instruct patients to avoid ototoxic medications and loud noise exposure without hearing protection.

With proper amplification, speech and language therapy, and educational programs, a patient with SNHL can fully participate in the totality of adult life, including social activities and work.

See the list below:

• Numerous educational methods are currently used for children with hearing impairment. These methods include auditory-oral training, cued speech, and total communication.

  • Auditory-oral training stresses acquisition of speech and language through enhancement of residual hearing. Lipreading skills, along with appropriate amplification, are heavily emphasized.

  • The cued speech approach is a visual-oral system that uses hand cues to supplement information received from lipreading. Hand cues alone are ambiguous, necessitating development of appropriate lipreading skills for language comprehension.

  • Manualism is a system of communication that stresses use of the manual alphabet (fingerspelling) and sign language for communication. American Sign Language (Ameslan) has been the language of the deaf population in the United States for more than a century. Ameslan does not follow English grammatical rules and has its own semantic system. Signed English uses syntax compatible with English grammar, giving people who are deaf knowledge of proper structure and usage of English.

  • The total communication method emphasizes manual, oral, and aural modes of communication. This method urges early use of residual hearing while accepting sign language as a normal means of communication. Speech and use of spontaneous expression are also encouraged.

• Educators, individuals with hearing impairment, and parents still disagree on the most advantageous method of communication. The method selected has a profound influence on a child's ability to someday fully participate in the totality of adult life, including social activities and work. No single educational program is correct for all children with hearing impairment, but, rather, decisions should be individualized for each child.

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