Jonathan M. Sherman, Eliot Shearer, Richard J.H. Smith, and Dana Suskind
Hearing loss in children is common in the United States with an estimated incidence of 1 to 2 per 1000 live births.1,2 During childhood, the prevalence increases. A 2010 report suggests that by adolescence, nearly 20% of children have a significant degree of at least unilateral hearing loss.3 This striking estimate, which has increased by a third in just a decade, places childhood hearing loss among the major public health concerns in the United States.4
Historically, delays in hearing loss diagnosis resulted in lost opportunity to intervene at a critical time in listening and spoken language development. Compelling evidence has linked timely identification and treatment to improved communication and school performance.5–7 Citing this data, the Joint Committee on Infant Hearing endorsed the concept of a Universal Newborn Hearing Screening (UNHS) in 2000.8Soon after, the U.S. Department of Health and Human Services’ initiative, Healthy People 2010, reinforced this goal, advocating nationwide UNHS by 1 month, diagnostic confirmation by 3 months, and early intervention enrollment by 6 months of age.9 UNHS expanded rapidly, and by 2005, every state had implemented a UNHS program. By 2006, approximately 95% of newborns in the United States were screened before hospital discharge.10
One of the challenges created by UNHS is that as more children are identified with hearing loss, no clear approach exists for determining the cause and identifying important associated medical conditions. In 2002, approximately 40,000 children were diagnosed each year in the United States alone, so that the classification of and medical work-up for a child identified with hearing loss is a dilemma that will be increasingly faced by not only tertiary care centers but by community otolaryngologists.11 At the same time, the number of diagnostic tests available are constantly increasing, resulting from ongoing strides in our understanding of disease pathogenesis and our ability to detect genetic determinants of disease. Experts feel that within the next decade, specific genetic testing which is being developed now will become the most important tool after history and physical examination in the work-up of a child with hearing loss, completely changing the diagnostic approach.
In this chapter we will attempt to provide a modern framework for approaching the medical work-up of a child identified with sensorineural hearing loss (SNHL).
Classifying Hearing Loss
Hearing loss is classically defined as conductive (involving the transmission of sound from the outside world to the oval window), sensorineural (involving the function of the cochlea, eighth cranial nerve, and central nervous system [CNS]), or mixed. The differential diagnosis of a child with conductive hearing loss is beyond the scope of this chapter, but it is important to recognize that conductive losses account for a substantial fraction of children identified with hearing loss. More than half of children aged 1 to 24 months, nearly a quarter of all UNHS failures, and up to 15% neonatal intensive care unit (NICU) babies with hearing loss have purely conductive loss.12
Hearing loss can also be classified as either bilateral or unilateral. While some controversy existed earlier regarding clinical significance, more than 2 decades of convincing evidence now shows that children with unilateral SNHL, such as those with bilateral disease, have significant deficits in psycholinguistic stills and school performance, as well as problems with sound localization and discerning speech-in-noise.13,14 Unilateral SNHL is caused by many of the same disease processes that lead to bilateral loss, and in fact, 20% of children identified with unilateral disease have progressive disease and 10% go on to develop hearing loss in the contralateral ear.15
Hearing loss is also characterized by the degree of severity. Like children with unilateral loss, those with mild and moderate hearing loss in one or both ears were once thought to be immune to the struggles of children with severe bilateral disease, but now several authors have shown that even mild hearing loss affects school performance, and that mild and moderate loss may be associated with learning disabilities.16,17 Severity of loss can be stable or progressive.
Etiology of Hearing Loss
In developed countries, it is estimated that two-thirds of childhood SNHL has a genetic etiology, 70% of which is not associated with any other phenotype and is therefore termed nonsyndromic hearing loss (NSHL) (Fig. 2.1).18 To date more than 59 genes have been implicated in nonsyndromic SNHL and more than 100 deafness loci have been determined where the gene has not yet been determined (http://hereditaryhearingloss.org/). SNHL that is not related to a genetic cause can be the result of prenatal and perinatal infection, exposure to ototoxic medicines in utero or in the postnatal period, NICU-related exposures and other perinatal conditions, autoimmune disease, or noise exposure (Fig. 2.1).
Genetic Nonsyndromic Hearing Loss
Eighty percent of genetic nonsyndromic hearing loss is autosomal recessive (autosomal recessive nonsyndromic hearing loss [ARNSHL], termed DFNB hearing loss), with the rest being mostly autosomal dominant (autosomal dominant nonsyndromic hearing loss [ADNSHL], termed DFNA), while X-linked and mitochondrial causes contribute less than 1%.19 Therefore, most children with genetic hearing loss otherwise appear normal and have parents with normal hearing. ARNSHL is generally prelingual and profound across all frequencies.20 To date, 38 genes and more than 60 loci have been causally implicated in ARNSHL.21 The single most common causative gene—GJB2(DFNB1), encoding gap junction protein connexin 26—accounts for approximately half of ARNSHL in many populations, and has been shown to account for approximately 25% of ARNSHL in the United States.22 Many mutations in GJB2 have been identified, including mutations that cause dominant deafness. Due to the diversity of mutations and the possibility of either other genetic or environmental modifiers, generalizations about hearing loss caused by GJB2 are difficult to make. However, it is clear that genotype-phenotype correlations exist based on the specific mutation.22–24 These data have shown that DFNB1 hearing loss is generally prelingual and ranges from mild to severe in degree.
Figure 2.1 Classification of sensorineural hearing loss (SNHL) by cause. Whereas the numbers vary from study to study, it is clear that at least two-thirds of childhood SNHL can be attributed to specific genetic causes. Clearly genetic factors also contribute to hearing loss in children with “acquired SNHL,” including susceptibility to ototoxicity of certain drugs. Regardless of the system used to classify etiologies, experts agree that the largest group among children with SNHL is inherited in an autosomal recessive pattern with no associated syndrome—children with no obvious cause by history or examination and normal hearing parents. AD, autosomal dominant; AR, autosomal recessive; CMV, cytomegalovirus.
Autosomal dominant mutations are diagnosed in a significantly smaller fraction of children with nonsyndromic SNHL. To date, 25 genes and more than 50 loci have been identified as causative for ADNSHL.21 Hearing loss in patients affected by ADNSHL is often progressive and postlingual although there are clear exceptions.
Genetic Nonsyndromic SNHL
Consider these diagnostic tests: GJB2 (connexin 26) testing, large throughput multiple gene assays in all children with SNHL with a clear family history or for whom an obvious cause is not readily apparent after physical examination, history, and audiologic evaluation (Table 2.1).
Genetic Syndromic Hearing Loss
Over 200 syndromes include hearing loss.25 Most are very rare, but several are important contributors to the overall incidence of SNHL.
Autosomal Dominant Syndromes
Some of the important autosomal dominant syndromes include branchio-oto-renal (BOR) syndrome, Waardenburg syndrome (WS), Stickler syndrome (STL), neurofibromatosis type 2 (NF2), and CHARGE (Coloboma, Heart defects, Atresia, Retardation of growth and development, Genitourinary disorders, and Ear abnormalities) syndrome.
Children with BOR syndrome have branchial cleft, otologic, and renal anomalies. Otologic findings include preauricular pits and tags and auricular abnormalities; middle ear anomalies including ossicular malformation, facial nerve dehiscence, and absence of the oval window; and inner ear anomalies including cochlear hypoplasia, lateral canal hypoplasia, or enlargement of the cochlear or vestibular aqueducts.26,27 Hearing impairment may be purely sensori-neural or conductive, but most often is mixed. BOR is most frequently caused by mutations in the EYA1 gene.
Consider these diagnostic tests: genetic consultation/testing for EYA1 mutations, renal ultrasound, urinalysis, computed tomography (CT) head in children with suggestive family history, external ear abnormalities, and branchial cleft anomalies.
Children with WS are classically described as having SNHL, a white forelock, heterochromia of the irises, and dystopia canthorum (lateral displacement of the medial canthi).28 There are four subtypes with a combined prevalence of 1:10,000. WS type 1 is classical WS, type 2 lacks the dystopia canthorum, type 3 (also called Klein-Waardenburg syndrome) has upper limb hypoplasia or contracture, and type 4 (also called Waardenburg-Shah syndrome) is associated with Hirschsprung disease. Hearing loss is usually congenital, can be bilateral, and is stable over time.29 Nearly 90% of WS type 1 is caused by mutations in PAX3; genetic contribution to the other types, however, is more uncertain.
Consider these diagnostic tests: genetic consultation/testing for PAX3 mutations in children with suggestive physical examination or family history.
STL has variable presence of SNHL, midline clefting, childhood myopia (except STL3, which is caused by mutations in COL11A2), joint hypermobility, and retinal detachment. The cluster of symptoms is related to abnormal collagen synthesis. Hearing loss is present in 40 to 60%, is often delayed in its presentation, preferentially affects high frequencies, and is most often mild. Despite this, a priority in STL (and any syndrome causing concomitant deafness and vision loss) is early identification for maximum efficacy of cochlear implantation if this becomes necessary.30
Consider these diagnostic tests: genetic consultation/testing for COL2A1 (STL1), COL11A1 (STL2), COL11A2 (STL3) mutations, ophthalmology evaluation in children with personal/family history of visual problems, craniofacial anomalies, and joint abnormalities.
NF2 is a cause of progressive SNHL characterized by the development of bilateral vestibular schwannomas. These patients often have other benign CNS tumors and posterior subcapsular lenticular opacities. Hearing loss is usually high-frequency, progressive, delayed until the second decade, and may be associated with vertigo, tinnitus, and facial nerve palsy.31
Consider these diagnostic tests: genetic consultation/testing for NF2 mutations, magnetic resonance imaging (MRI) brain, ophthalmology evaluation in children with family history, other cranial nerve abnormalities, headache, and visual complaints.
CHARGE syndrome, affecting 1 in 10,000 children, may be inherited in an autosomal dominant pattern, but the majority of cases result from de novo mutations in the chromodomain helicase DNA-binding protein-7 gene (CHD7). Typically, infants with CHARGE syndrome have bilateral mixed type hearing loss with a wedge-shaped audiogram having a flat air conduction curve intersecting at low frequencies with a descending bone conduction and have specific ear anomalies seen on imaging studies (Fig. 2.2).32
Figure 2.2 Temporal bone computed tomography scan of a child with CHARGE (Coloboma, Heart defects, Atresia, Retardation of growth and development, Genitourinary disorders, and Ear abnormalities) syndrome. Common inner ear anomalies typically seen in CHARGE syndrome include (A, B) underdevelopment or agenesis of the cochlea beyond the basal turn and (C, D) hypoplastic vestibule and semicircular canals.
Consider these diagnostic tests: genetic consultation/testing for CHD7 mutations, then pediatric cardiology, urology consultations, and CT head in children with suggestive physical examination result, growth delay, history of feeding difficulties due to choanal atresia, cryptorchidism, undescended testes, hypospadias, or external ear anomalies.
Autosomal Recessive Syndromes
Syndromes causing SNHL inherited in an autosomal recessive pattern include Pendred syndrome (PS), Usher syndrome (USH), and Jervell and Lange-Nielsen syndrome (JLNS).
PS accounts for roughly 10% of all hereditary deafness with an estimated prevalence of 1 in 10,000 individuals.33 PS is caused by a mutation in the PDS (SLC26A4) gene that encodes an anion transporter present in the inner ear and thyroid. PDS mutations are also found in 86% of patients with enlarged vestibular aqueducts (EVA), leading authors to suggest that EVA is the most consistent finding in PS. Because of this, CT scan abnormalities are often the first clue toward PS diagnosis after SNHL diagnosis (Fig. 2.3).34 In the past, a perchlorate discharge test was done to confirm PS, but low sensitivity has made genetic testing the preferred examination in suspected patients.35 Most children with PS respond to cochlear implantation favorably.36
Figure 2.3 Computed tomography scan of temporal bone of a patient with Pendred syndrome (A) shows typical enlarged vestibular aqueducts (B) bilaterally (arrowheads).
Consider these diagnostic tests: genetic consultation/testing for SLC26A4 mutations, thyroid function tests, CT head in children with EVA, cochlear anomalies on CT scan, goiter, and suggestive family history.
USH is characterized by SNHL, retinitis pigmentosa, and vestibular dysfunction, and taken together are the most common cause of deafness-blindness in the United States.37 There are three types of USH. USH1 is characterized by severe congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa developing in early childhood; USH2 has hearing loss that is moderate, no vestibular dysfunction, and later onset of retinal degeneration; and USH3 is characterized by progressive hearing loss and vestibular dysfunction with variable retinal disease. Because USH is relatively common and cannot otherwise be differentiated from ARNSHL early on, and because early bilateral implantation is critical for children with USH in light of the vision deficits, all children with bilateral SNHL and without obvious cause after history and examination should have an ophthalmological examination which may include electroretinography (ERG).
Consider these diagnostic tests: genetic consultations/testing for CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, and USH2A mutations, ophthalmology consultation, and ERG in any child with presumed bilateral, symmetric ARNSHL, or history or examination suggestive of USH.
JLNS is a form of congenital deafness that is associated with a prolonged QT interval seen on electrocardiogram. Hearing loss in children with JLNS is most commonly profound, bilateral, and present at birth. Like other long QT syndromes, syncope is sometimes present in affected children, but the presenting symptom may be ventricular arrhythmia and sudden death, thus making this condition an important one to rule out in congenitally deaf children.38
Consider these diagnostic tests: genetic testing/consultation, electrocardiography (EKG), pediatric cardiology consultation in any child with personal/family history of syncope, long QT syndrome, or family history of sudden death.
Syndromes causing SNHL inherited in an X-linked pattern include Alport syndrome (AS) and X-linked deafness syndrome.
AS is a common disease affecting renal function. Its prevalence is estimated to be 1 in 5000. This disease can be inherited in an autosomal recessive or dominant pattern, but sex-linked inheritance accounts for 80% of patients. In addition to hematuric nephritis, patients with AS suffer from congenital cataracts and progressive SNHL. The hearing loss is present in 55% of affected patients, is high-frequency, and typically presents in the second decade of life.39
Consider these diagnostic tests: genetic testing/consultation, urinalysis, renal electrolytes, complete blood count (CBC), ophthalmology consultation in children (mostly male) with hematuria, suggestive eye abnormalities, personal/family history of other renal disease, and thrombocytopenia.
DFN3, an X-linked form of deafness, is characterized by malformation of the labyrinth, creating an abnormal communication between the cerebrospinal fluid (CSF) and perilymph. The cochlea is shortened and lacks bony separation from the internal auditory canal and the facial nerve course is altered. Although patients usually have mixed hearing loss, stapes surgery is not recommended due to the risk for a perilymphatic gusher.40
X-linked Deafness Syndrome
Consider these diagnostic tests: genetic consultation, MRI in males with a suggestive family history and progressive mixed-type hearing loss.
Syndromes Related to Mitochondrial Disorders
Maintenance of ionic potentials is fundamentally important to cochlear function and the demand for energy in this tissue is high. Therefore, mitochondrial diseases can be associated with SNHL. Examples include mitochondrial encephalopathy, lactic acidosis, stroke syndrome, Kearns-Sayre syndrome (heart block and progressive ophthalmoplegia), and MERRF (myoclonic epilepsy and red ragged fibers) syndrome. Patients with these disorders are prone to late-onset, progressive, and bilateral high-frequency hearing loss.3
Consider these diagnostic tests: genetic, ophthalmology, neurology, and cardiology consultations in children with suggestive histories, retinitis pigmentosa, and suggestive family histories.
Nongenetic Hearing Loss
There are a large number of insults that occur during fetal life, in the peri- and postnatal periods, and later that cause SNHL. The largest nongenetic cause of SNHL is infection—both in children identified by failed UNHS and among children who develop hearing loss later. Cytomegalovirus (CMV) is the most common intrauterine infection and a major cause of sensorineural deafness worldwide.41,42 The prevalence of CMV infection is so high (1% of all live births in the United States) that even with only 14% of infected children developing SNHL, CMV accounts for 15 to 20% of all bilateral moderate to profound loss.43 Ten percent of CMV-infected neonates are symptomatic at birth, and most will fail UNHS. Of the remaining 90% who are normal at birth, between 7.5 and 10% will eventually develop hearing impairment. Many also eventually develop cognitive delay and other neurological disease, vision loss, growth retardation, hepatosplenomegaly, hematological abnormalities, and various cutaneous manifestations. The median age of detection is 27 months among children who originally passed newborn hearing screens.44
Consider these diagnostic tests: CMV titers in mother and child, CMV quantitative polymerase chain reaction, then CT head, infectious disease and developmental pediatric consults in any child diagnosed with SNHL presenting in the first 3 weeks of life.
Other important intrauterine infections include toxoplasmosis, rubella, and syphilis. Treatment is available and effective if administered early for many infectious causes of neonatal SNHL, making selective screening important.
Congenital TORCH Infection
Consider these diagnostic tests: toxoplasmosis, Rubella, CMV, herpes simplex virus, syphilis, vericella-zoster virus titers in neonates with suggestive physical examination results and pregnancy history.
Another important risk factor for SNHL is NICU admission. Before universal screening, directed hearing screens were administered to neonates in the intensive care unit because of their high risk status, with prevalence of 3.2%.45Several environmental risk factors and associated conditions are hypothesized as causative, including increased ambient noise, perinatal complications such as hypoxia and acidosis, inherited syndromes, hyperbilirubinemia, meningitis, extended positive pressure ventilation, extracorporeal membrane oxygenation (ECMO) requirement, and ototoxic drug administration. In a recent, large retrospective study, neonates from the NICU who failed UNHS were found to be significantly more likely to have dysmorphic features, low appearance, pulse, grimace, activity, respiration (Apgar) score at 1 minute, sepsis, meningitis, cerebral bleeding, and cerebral infarction compared with controls.46
Severe hyperbilirubinemia and the resultant kernicterus have been long established as an important cause of SNHL in neonates. The proposed mechanism of injury in this case is auditory nerve myelinopathy.47 The hearing loss that results falls into a subclass of SNHL called auditory neuropathy (AN)—an SNHL that is defined by normal outer hair cell function with an abnormal auditory brainstem response (ABR). AN is an abnormality in the neural processing of auditory stimuli. AN was first described in 1996, and since then its identification has increased dramatically. Classically, AN is diagnosed when children have speech recognition scores which are disproportionately low representing an inability to decode speech and language in the setting of normal or slightly elevated audiogram pure-tone thresholds. In fact, AN as it is defined is a group of hearing losses that are diverse in pathophysiology and treatment. Abnormalities in synchronizing inner hair cell firing and nerve conduction—now more appropriately termed “auditory dyssynchrony”—make up a form of AN for which implantation is clearly beneficial.48
The fact that children in the NICU are at higher risk for developing AN has implications for UNHS protocols. The Joint Committee on Infant Hearing in 2007 recommended screening these high-risk neonates with ABR, as AN is missed with screens that only test outer hair cell function. NICU graduates are also at increased risk for delayed, progressive hearing loss, and so they must be carefully screened for changes in hearing during childhood.
Consider these diagnostic tests: CT internal auditory canals (IACs) or MRI IACs in children with suggestive ABR or audiogram, history of NICU admission or hyperbilirubinemia and who are cochlear implant candidates.
Bacterial meningitis is the most common cause of acquired SNHL in the postnatal period. Roughly a third of affected children develop at least a mild hearing loss.46 This fact and the risk of postinfectious cochlear ossification make close audiological follow-up and early cochlear implant evaluation critical.
Ototoxic drugs can affect hearing in utero and at any point during childhood. Drugs that pose a risk include aminoglycosides, for which there is a genetic predisposition47,49; other antibiotics such as erythromycin, vancomycin, and tetracycline, which have a more pronounced ototoxic affect in children with renal impairment; certain chemotherapeutic agents, including cisplatin, 5-fluorouracil, bleomycin, and nitrogen mustard; salicylates, which cause SNHL that is completely reversible with discontinuation of the drug; and high-dose intravenous loop diuretics, in which the effect is largely temporary and potentiated by other ototoxins.50 Maternal use of alcohol and illicit drugs during pregnancy may also affect a child's ability to hear. Of all these drugs, cisplatin is generally accepted as the most ototoxic, causing hearing impairment in up to 25% of patients.51
Another important nonhereditary cause of SNHL is noise. While increased noise exposure in the NICU is one theoretical risk factor, of greater concern is noise trauma in older children. The prevalence of noise-induced hearing loss among children has increased dramatically in the last several decades, with most recent estimates approaching 20%.3,4 An increase in use of personal listening devices has been blamed. With supra-aural headphones, recommendations limit noise exposure to 1 hour daily at 60% maximal volume. These types of headphones are clearly safer than insert headphones (earbuds).52 Noise-induced hearing loss is typically sensorineural and often shows frequency dip at 4 kHz, the resonant frequency of the external canal.
Cogan's syndrome is an autoimmune rheumatic condition causing SNHL in older children and young adults. Following recovery from an influenza-like infection, affected individuals develop interstitial keratitis, vasculitis, and vestibuloauditory symptoms including progressive bilateral SNHL. No definitive test exists, but when symptoms and an elevated erythrocyte sedimentation rate (ESR), leukocytosis, and thrombocytosis are suggestive, prompt treatment should be initiated with steroids and other immunosuppressants to halt progress of hearing and vision loss.53 Other autoimmune conditions associated with SNHL—also found in older children—include systemic lupus erythematosus, juvenile rheumatoid arthritis, and juvenile diabetes.
Autoimmune-Related Childhood SNHL
Consider these diagnostic tests: ESR, antinuclear antibody, rheumatoid factor, CBC, ophthalmology consultation, glucose testing in older children with suggestive history, particularly with personal/family history of autoimmune disorders.
It is important to note that anatomic anomalies of the inner ear—often unrelated to any known underlying genetic cause—are a major cause of SNHL in children. In fact, roughly a quarter of all children with congenital SNHL have some inner ear malformation detectable by modern imaging.54,55 The most common is Scheibe dysplasia, or cochleosaccular dysplasia. The most severe bony anomaly is Michel aplasia, or complete labyrinthian aplasia. Incomplete partition, or Mondini dysplasia, is characterized by only 1.5 turns in the cochlea, is the most common congenital cochlear malformation, and is associated with PS and EVA.
Anatomical Anomalies of the Inner Ear
Consider these diagnostic tests: genetic testing/consultation, CT temporal bones in all children with SNHL for whom an obvious cause is not readily apparent after physical examination history, and audiologic evaluation and connexin 26 testing is negative.
Medical Evaluation of a Child with SNHL
Increasing numbers of children with SNHL are being identified through screening, and the tests available to classify the underlying cause of that hearing loss are growing in number and becoming more complex. In the current environment of increasingly limited resources, this has created a dilemma for which there is still no clear answer.
Each provider or institution approaches the work-up of SNHL differently. In general, a great deal of information is gained through a thorough history and physical examination including complete audiographic analysis, and some experts suggest that this is the only universally required step. Others weigh the yield of each test and the danger of a missed diagnosis against its cost, and choose from a variety of blood tests, genetic tests, imaging, other ancillary examinations and specialist consults.
In the next several years, as we have an exponentially improved understanding of the genetic determinants of hearing loss and methods for determining them, the most efficient work-up of children with SNHL will change so that genetic testing will become the most important part of a diagnostic work-up of a child with SNHL after history, physical examination, and audiometry.
A complete history is imperative and should address multiple issues including: (1) exposure to intrauterine infections (toxoplasma, rubella, CMV, herpes simplex virus, human immunodeficiency virus, and syphilis); (2) maternal and child vaccination history; (3) maternal metabolic disorders including diabetes or hyperthyroidism; and (4) the use of toxic agents during pregnancy (ethanol, tobacco, illicit drugs, ototoxic medications). The birth history should include Apgar scores, episodes of hypoxia, hyperbilirubinemia, pulmonary hypertension, low birth weight, and ECMO requirement. Any history of head trauma or noise exposure, meningitis history, fainting spells, or visual problems should also be noted.
Family history is essential and may help identify a genetic basis for the hearing loss. A history of consanguinity increases the possibility of an autosomal recessive disorder.
A thorough physical examination first must rule out conductive components to the hearing loss. Possible syndromes should be ruled out with attention to the presence of endocrine abnormalities (thyroid nodules, diabetes), visual anomalies (retinitis pigmentosa, retinal detachment), craniofacial anomalies (dystopia canthorum, aural atresia, branchial anomalies, cleft palate), cardiac anomalies, other cranial nerve palsies, and pigmentary anomalies (heterochromic irides, white forelock).
Aside from the history and physical examination a complete audiologic evaluation is the only testing that some experts feel is uniformly required in the work-up of childhood SNHL. If there is a family history of dominant hearing loss, the audiogram often displays characteristic gene-specific patterns (Fig. 2.4). For example, a “cookie-bite” pattern can be caused by mutations in COL11A2 (DFNA13), while mutations in WFS1 usually cause low-frequency hearing loss that rises to normal in the high frequencies (DFNA6/14/38). These differences are exploited by an online resource called AudioGene. AudioGene is a support vector machine trained to predict the genetic cause of hearing loss in dominant families by using pattern recognition or audioprofiling56 (Table 2.2).
The SNHL-specific diagnostic yield of laboratory testing has been shown to be as low as 0 to 2%57 and is generally not recommended. One notable exception is in the evaluation for intrauterine CMV infection. In several European countries, CMV screening is part of a routine prenatal work-up for all pregnant women, but at present, this policy has not been adapted in the United States. Because CMV is causative in 15% of bilateral hearing loss in childhood, efforts are being made to develop an acceptable neonatal CMV screen, a CMV vaccine, and CMV treatment for infected neonates.58,59 At present, CMV culture of saliva, urine, or serum can confirm CMV infection in 6% of neonates failing UNHS.60 All children presenting before 3 weeks of age should be tested for CMV titers (with maternal testing as well).
Figure 2.4 Typical audiogram appearances of selected causative mutations.
The role of EKG as a screening examination for all children after confirmed SNHL is an area of contention and most experts recommend an EKG only with a family history of syncope, arrhythmia, or sudden death.61
The role of genetic testing is growing as comprehensive testing becomes accessible and cheaper. These changes reflect the concurrent development of high-throughput genetic screening by multiple centers.62–70 At the same time, the fraction of SNHL attributed to known, testable genetic defects is growing.
Several investigators have suggested that because 20% of children with severe-to-profound bilateral SNHL have causative mutations in GJB2, a cost-effective paradigm in the face of this type of hearing loss begins with mutation screening of GJB2. The identification of mutations in this gene would obviate other ancillary tests, saving health care dollars while at the same time practicing evidence-based medicine.66 In 2007, a nationwide survey to pediatric otolaryngologists showed that nearly 70% follow this paradigm and order GJB2 testing routinely on the first visit.
In the future, the most cost-effective evaluation of childhood SNHL will likely involve a permutation of this paradigm, with more extensive genetic testing as the first test ordered. Recent advances in genetic screening methods now allow sequencing of millions of bases simultaneously thus making comprehensive genetic testing possible for deafness. The emerging screening methods are summarized in Table 2.1.63–65
The need for imaging in all patients with SNHL and the ideal imaging modality for these children remain controversial topics. Imaging is essential when a child is a candidate for cochlear implantation, and the complementary information provided by CT and MRI makes both tests helpful for treatment planning.61
High-resolution CT scanning is thought by many to be the preferred modality in evaluating nonacute SNHL as it allows for evaluation of bony abnormalities of the cochlea, vestibular apparatus, internal auditory canal, or temporal bone otherwise. A review of 351 children with SNHL in 2009 showed that 31% had abnormalities on CT, the most common being EVA (15%).54 A recent CT and MRI comparison in a series of children with unilateral and asymmetric SNHL advocated CT, as 41% of CTs showed abnormalities while only 30% of MRIs were read as abnormal.
MRI, however, offers benefits of increased soft tissue resolution, which is important in evaluating the cochlear nerve and membranous labyrinth. A 2008 retrospective evaluation of 170 children with SNHL showed that MRI demonstrated inner ear abnormalities in 38% of children with bilateral moderate to profound hearing loss and in 62% of children with unilateral disease. Absence of the cochlea nerve was seen in 21 children in this study, one-third of whom would be missed by CT. By CT size criteria, one-third of these would have been missed.67
MRI is particularly useful in patients with AN/auditory dysynchrony.68 A review of 118 children with this diagnosis demonstrated at least one MRI abnormality in two-thirds of patients. Common abnormalities that became apparent with MRI (and not with CT) in these patients were cochlear nerve deficiencies (28%), brain abnormalities (40%), and prominent temporal horns (16%).
Half of pediatric otolaryngologists order ophthalmologic consultation as part of a routine SNHL evaluation, and half order a genetic consultation.61
The role for ophthalmologic evaluation is supported by a 2002 study which reported ocular abnormalities in 31% of children referred after SNHL diagnosis. As a result of an evaluation of 49 patients, 4 children underwent nonoperative intervention, 2 had surgery, 2 received prescription lenses, and 2 received diagnosis of a hearing loss related syndrome.69 In the algorithm suggested below, only some children are referred for formal ophthalmologic consultation as a part of the diagnostic process, but all children with SNHL should undergo vision screening as part of treatment to optimize sensory input.
Otolaryngologists refer families for genetic consultation not only because such an evaluation can be helpful in identifying syndromic causes of SNHL, but also because explaining the genetics of SNHL and its implications for future children is complex. The overall recurrence chance for a normal hearing couple to have an additional child with hearing loss after the birth of one child with presumed ARNSHL is 17.5%,70 but that estimate changes in various situations, and most otolaryngologists are unable to provide accurate data to families.61,71
Suggested Algorithm for Medical Work-Up of a Child with Newly Diagnosed SNHL
All children with newly diagnosed SNHL should have a complete history (including family history), physical examination, and complete audiology evaluation (Fig. 2.5). Siblings and parents of all children without an obvious nonhereditary cause of SNHL should get audiograms, both for their own care and to aid the diagnostic process. All children identified before 3 weeks of age should be evaluated for CMV infection. If a syndrome is suggested by the basic evaluation, additional syndrome-specific testing should be considered.
If the SNHL is mild and unilateral, the child should be followed carefully for progression of the hearing loss, obtaining a CT if necessary. CT scan should be considered for fluctuating hearing loss as well. If the child has unilateral SNHL that is at least moderate in severity, MRI should be completed.
If the child has bilateral SNHL of any degree, genetic testing should be obtained. In the near future, this will include all genes known to cause nonsyndromic hearing loss. An ophthalmological examination should be completed if history, physical examination, and family history are not helpful. CT should also be considered in these children.
If the child is a candidate for cochlear implantation, both MRI and CT should be completed.
The evaluation of childhood SNHL is evolving. This change is seen most clearly in the increasing role played by genetic testing. As this type of testing becomes cheaper, it can be used as a platform from which other informed and evidence-based decisions can be made in the appropriate evaluation of the child with hearing loss.
Figure 2.5 Suggested algorithm for the work-up of children with sensorineural hearing loss. ABR, auditory brainstem response; CMV, cytomegalovirus; CT, computed tomography; MRI, magnetic resonance imaging; SNHL, sensorineural hearing loss; wk, week(s).
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