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Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge.


The correct and timely diagnosis of hearing loss in children is a relevant topic as, if not properly recognized, hearing disorders may harmfully impact children development and on quality of life [1]. Universal newborn hearing screening (UNHS) represents a critical instrument for the early detection of hearing loss in infants at birth [1-4]. However, not all cases of hearing loss can be identified by UNHS, especially as late onset or progressive forms of hearing disorders are not evident at birth. Therefore, it is necessary to monitor carefully every child presenting pre-, peri-, and post-natal risk factors for hearing impairment, as already suggested by the Joint Committee on Infant Hearing in 2007 [1].

The accurate diagnosis of hearing loss in children and the appropriate rehabilitation is challenging; it is often necessary a stepwise multidisciplinary approach in which several specialists are involved, such as otolaryngologists, audiologists, pediatricians, neonatologists, geneticists, neuroradiologists, speech therapists [5]. It is mandatory to recognize hearing impairment in children, even a moderate loss, as early as possible, and to provide the proper therapeutical and rehabilitative program, in order to guarantee the best opportunities to adequately develop language, cognitive, and relational skills [1].


The PubMed, Embase, and Cinahl databases were searched for the last 5 years (from January 2012 up to December 2016). Full-text articles were obtained in cases where the title, abstract, or keywords suggested that the study may be eligible for this review. The medical subject heading (MeSH) terms used included: hearing loss, children, universal newborn hearing screening, cytomegalovirus (CMV), hearing rehabilitation, language development, and hearing aids.

The search was conducted also according to PRISMA criteria/guidelines ( it was carried out independently and restricted to articles in English (Table 1). Initially, the total number of article identified was 617; other 26 articles were also identified from references in the published literature when all authors agreed about the reliability and importance of these manuscripts, for a total of 643 articles. Inclusion criteria were clinical series and review articles. Exclusion criteria were no availability of a full text, manuscripts not being in the English language, and case reports.

Therefore, authors critically evaluated the 146 selected articles, by reading abstracts and/or texts, to decide whether the identified articles were relevant to this search or not. In this case, inclusion criteria were: for clinical series, articles with an adequate group of patients studied (n>20); for reviews, articles published on relevant journals and articles showing a rigorous methods and rigorous reporting. Finally, 86 articles resulted appropriate for this review according to all authors.


Hearing loss in children is a relevant health issue, both for its prevalence and for the related social and personal impact. Epidemiologic data reported in literature about the wide prevalence of hearing loss in children, and this fact is due to different reasons, such as dissimilar criteria used to define hearing disorders, different instruments used to define hearing loss, and divergent groups of children considered. However, the reported worldwide prevalence of hearing loss in infancy is 1.12/1000 newborns, considering the congenital forms, and 1.33/1000, also considering those acquired and those with late onset [6].

In 2007, the Joint Committee on Infant Hearing updated the principles of UNHS, which represents the first step of the diagnostic work-up of hearing loss in children, within the first month of life [1]. UNHS allows to identify not only those affected by profound hearing loss but also those affected by moderate-severe hearing loss. When a child fails the UNHS, he/she has to be addressed to an audiological evaluation, in order to organize a proper and individualized diagnostic work-up[1,2]. Unfortunately, the late onset and the progressive forms of hearing disorders are not evident at birth and cannot be identified at the UNHS [7]. For this reason, the Joint Committee on Infant Hearing proposed a list of risk factors associated to permanent form of childhood hearing loss, suggesting that every child presenting pre-, peri-, and post-natal risk factors and/or other listed characteristics has to be carefully monitored through audiological assessments within the first years of life (at least until the age of 24-30 months, and of 6 years in case of congenital CMV infection particularly) [1, 8, 9].

Etiopathogenesis of Moderate-Severe Hearing Loss in Infancy

Moderate-severe hearing loss can be congenital or acquired and further classified in pre-, peri-, and post-natal, considering its period of occurrence. Neonatal hearing loss can be due to problems correlated to pregnancy, delivery, and/or the immediate post-natal period [10-13].

Pre-natal hearing loss

During the embryological period, the auditory system is reported to be particularly vulnerable to toxic and teratogenic agents: ototoxic drugs (i.e., aminoglycosides, chemioterapics) used during gestation or drugs/alcohol abuse can be responsible of inner ear alterations, such as mother metabolic disorders (i.e., renal or liver failure, diabetes mellitus) [10, 14]. In particular, fetal alcohol syndrome is a consequence of the alcohol teratogenic effect during pregnancy, and it is characterized by a growth defect, typical facies, microcephaly, skeletal anomalies, mild-moderate mental retardation, behavioral anomalies, congenital heart condition, and hearing loss also [15]. Ototoxicity occurs due to cochlear hair cells and irreversible death; it may also become evident in case of low hematic drug concentration and short therapies for a particular genetic predisposition (a mitochondrial DNA mutation) [16]. Furthermore, ototoxicity increases when other drugs are used in association [17]. Also, gestational infections represent a pre-natal cause of congenital hearing impairment; in particular, CMV infection can be responsible also for late onset of sensorineural hearing loss (SNHL) [18].

Peri- and Post-Natal Hearing Loss

Among peri- and post-natal conditions at risk for neonatal hearing loss, NICU (Neonatal Intensive Care Unit) hospitalization . 5 days plays an important role, as it is reported to increase hearing loss incidence by about 5-10 times, if compared with general newborn population [17]. It may be related not only to NICU equipment environmental noise but also to therapies used, such as ototoxic drugs, or mechanical ventilation for more than 5 days. Prematurity is not reported to be a risk factor itself, but the association of several risk factors may represent a predisposition to develop hearing impairment [17]: very low birth weight (<1.500 g), peri-natal asphyxia, jaundice [1]. Numerous congenital infections have been linked to hearing loss, mono or bilateral, sometimes progressive [10]. Viral infections, such as varicella, herpes, influenza, and mumps, may be responsible for SNHL as much as a bacterial meningitis (Streptococcus pneumoniae, Neisseria meningitidis) [10]. The most frequent congenital infection is CMV, as vaccines have reduced the incidence of rubella, mumps, and measles. Congenital CMV infection prevalence is estimated in about 0.64% children at birth [19]. It can be a primary or a recurrent infection; only 10% of infected children are symptomatic at birth, and hearing loss may be present in about half of the cases. CMV-related sensorineural hearing defect may be of mild-moderate degree, mono- or bilateral, typically fluctuating and, for most of the cases, with a delayed onset [18-22]. Also, many cases of idiopathic hearing loss in children with a late diagnosis are consequences of an unknown congenital CMV infection. In 2009, Boudewyns et al. [23] tested, through real-time PCR, DNA obtained from neonatal Guthrie cards of infants who failed UNHS and children with non-congenital SNHL, searching for CMV DNA. They found CMV-positive results in 7.3% of the children of the two study groups.

Trauma represents another acquired post-natal etiology of hearing loss; generally, a post-traumatic labyrinth damage can be responsible of a monolateral conductive, sensorineural, or mixed hearing defect [24, 25].

However, about 60% of congenital hearing loss is genetic and it can be syndromic (30% of cases) or non-syndromic (70% of cases) [26-29].

In the last 20 years, genetic diagnosis has experimented many progresses [30]. In particular, the introduction of NGS (next-generation sequencing) and MPS (massive parallel sequencing) for the molecular testing of hearing loss has allowed the examination of large gene panels [31, 32]. Because of the improved diagnostic techniques, about 160 genes have been linked to hearing impairment so far. Many genes have been discovered to be involved in auditory function: mutations of proteins implicated in adhesion between hair cells, ionic transport, neurotransmitter release, and cytoskeletons of inner ear cells may be linked to cochlear disorders [33]. An updated official database of recognized monogenic non-syndromic types of hearing loss is available at the Hereditary Hearing Loss Homepage (http://hereditaryhearingloss. org/) [34]. Every non-syndromic hearing loss (NSHL) is classified considering the time of its discovery and its transmission model. Most cases of NSHL have a recessive transmission model (about 80%); the remaining cases are autosomal dominant, X-linked, and mitochondrial [18, 35-40].

The most frequent recessive form of SNHL (more than 50% of cases and 20%-25% of all causes of congenital hearing disorder [41]) is known as ARNSHL DFNB1A, according to the classification in Hereditary Hearing Loss Homepage [34]; it is linked to mutation of GJB2 (gap junction beta-2) gene, coding for a transmembrane protein called connexin 26 [5, 37, 42-44]. Also, mutation of GJB6, coding for connexin 30, has been reported to be associated to hearing dysfunction (ARNSHL DFNB1B). Generally, GJB2 and GJB6 hearing defects are mild-to-profound SNHL, bilateral, and not necessarily preverbal [45-47].

It has also been reported that some genes, such as GJB2, may have a different pattern of inheritance according to the specific mutation: a particular mutation of GJB2 is linked to an autosomal dominant form of hearing impairment (DFNA3A) [34]. Moreover, some other genes may occur as either non-syndromic or syndromic, such as SLC26A4, which is responsible of a non-syndromic autosomal recessive hearing loss (DFNB4), the second most frequently found after GJB2 [48]. Other common causative genes for autosomal recessive hearing disorder are MYO15A (encoding for myosin XV), OTOF (encoding for otoferlin, whose mutations are linked to an auditory neuropathy/dissynchorny), and CDH23 (encoding cadherin-23, whose mutations may also be responsible of Usher syndrome type 1D) [41, 49].

Hearing loss associated with autosomal dominant and X-linked transmission method are typically postverbal, with a variable hearing loss, generally progressive [30, 50, 51]. These forms can also be easily detected while studying the family tree. Among the most frequently identified genes related to hearing loss with autosomal dominant inheritance, there are: WFS1, TECTA, COCH, and KNCQ4 [41]. POU3F4 is the most frequent genetic mutation related to X-linked non-syndromic hearing impairment commonly associated with cochlear hypoplasia and a bulbous malformation of the internal auditory canal [41].

Mitochondrial mutations are mainly related to moderate-severe hearing loss; the phenotypic expression may be extremely variable, often multisystemic, considering other different factors, genetic, and not [36, 52].

Syndromic hearing loss is associated with dimorphisms and/or signs/symptoms/malformations of other organs [53, 54]. More than 400 syndromes linked to hearing loss have been described so far, but the diagnosis may be difficult as: (i) the genetics of these syndromes is heterogeneous and with a variable penetrance and (ii) different mutations of the same gene may be linked to both non-syndromic and syndromic hearing loss [55]. Waardenburg syndrome (characterized by mono- or bilateral mild-to-severe SNHL, associated with typical hair, skin, and eyes dyschromic manifestations) and branchio-oto-renal (BOR) syndrome (involving branchial arch anomalies; inner, middle, and external ear malformations; hearing loss; and kidney defects [56]) are among the most frequent causes of autosomal dominant syndromic hearing loss.

Pendred syndrome is the most common autosomal recessive syndrome of hearing impairment [55]. It is due to PDS gene mutation, encoding for a protein called pendrin (also known as SLC26A4, solute carrier family 26, member 4), involved in calcium and iodine transport; it has a recessive autosomal transmission modality. Pendred syndrome is characterized by congenital or generally preverbal bilateral profound SNHL, associated with non-endemic goiter, temporal bone anomalies, enlarged vestibular aqueduct, and, sometimes, mental retardation and cerebellar signs. Usher syndrome, with autosomal recessive inheritance, represents the most common form of hearing impairment and vision loss during infancy [55].

Diagnostic Work-Up of Moderate-Severe Hearing Loss in Children

The diagnostic work-up of hearing loss in children is often difficult and requires a multidisciplinary approach [5, 57-60].

Particularly, the identification of the hearing impairment etiology, when possible, is important. After an accurate personal and familiar history taking and an otoscopic evaluation, a complete physical examination is the first step in the approach to the diagnosis of hearing loss in children [1, 61-63]. In case of external ear malformations (i.e., auricle abnormalities, external auditory canal atresia, or stenosis) which may be isolated or associated with other physical anomalies (therefore configuring a syndrome), it is mandatory to evaluate the auditory function. In presence of preauricular pit or tag, which can occur sporadically or inherited, and can be associated with a syndrome (such as BOR syndrome), the assessment of hearing function is still controversial [64]; audiometric testing has been recommended in case of syndromic forms, but there is no consensus on hearing investigation in sporadic cases, as the role of isolated preauricular pits as a risk factor for auditory impairment is still unclear [65-67].

During the general evaluation, it is also important to evaluate the presence of other abnormalities, such as skin dyschromia, eye irregularities, renal dysfunction, particularly when suspecting syndromic forms and in case of familiarity for hearing loss [1, 2, 68].

Family history of hearing impairment represents a risk factor to be considered during the diagnostic work-up [69]; a history of hearing impairment is mentioned as risk factor for both congenital and post-natal hearing loss by the Joint Committee on Infant Hearing [1, 70]. It has been recommended to accurately analyze at least three generations in the family tree, especially in the suspicion of an autosomal dominant hearing loss [67, 71].

Likewise, a genetic assessment is important, as about 60% of cases has a genetic origin. Even more important is the genetic investigation in case of hearing loss occurring in an inbred family, as it increases the prevalence of recessive forms [30]. The genetic evaluation is often long and difficult and it is based on genetic tests performed in programmed stages, on the basis of clinical suspects [18, 36, 72, 73]. The first step is always represented by a clinical genetic evaluation; therefore, in order to plan the appropriate molecular studies, auxologic parameters and family tree are registered [69]; facial dysmorphisms and major (such as labiopalatoschisis) and minor anomalies (such as little auricle, fifth finger clinodactily, pit, tag, renal malformations, branchial arch development anomalies) are searched [18, 36]. Frequently, a diagnosis is suggested by facial features, typical phenotypes of syndromic dysmorphisms [74]. Also, a unilateral hearing loss could suggest a genetic etiology [75, 76]. For every child with a negative GJB2/GJB6 mutation or a negative CMV test, a clinical follow-up has been recommended in order to assess periodically potential dismorphological patterns that could relate to a particular syndrome [74].

The NGS and MPS technology has improved the genetic approach to hearing loss [77]. There are important factors to be considered when choosing a genetic test, such as patient's history and phenotype [78]. The identification of a genetic hearing disorder is important as it may improve prognostic accuracy and may allow a correct genetic counseling for the affected patient and relatives at risk [79, 80]. Also, the genetician may provide information to parents among inheritance modalities and the pre-natal diagnosis if available [81, 82].

Neuroradiologic examination is another necessary diagnostic stage: temporal bone CT (computed tomography) scans and brain, brainstem, pontocerebellar angle, inner ear and central auditory system MRI (magnetic resonance imaging) are recommended in all permanent hearing loss in children and, frequently, they are complementary examinations [83]. CT scans are essential in case of cranial trauma, but also in case of pre-surgical evaluation before cochlear implant surgery, in case of cholesteatoma, or in case of suspected middle ear malformation [84-86]. MRI has a high degree of definition of labyrinth fluid contents; it is suitable in the inner ear and central auditory system evaluation [83].

A serological assessment is always important; when a congenital CMV infection is suspected, also, a retrospective diagnosis is possible through viral DNA PCR research in Guthrie card blood spots or in urine sample. In order to differentiate a pre-natal CMV infection from a peri- or post-natal infection (which are not associated to a significant risk of hearing impairment), the CMV DNA research has to be performed within two weeks of birth [23, 87, 88]. An early diagnosis of congenital CMV infection is fundamental in order to set up the appropriate antiviral therapy [89-91]. Anti-CMV vaccine is currently under evaluation and may become available in the future.

Other important examinations that can facilitate the identification of hearing loss etiology are electrocardiogram and QT evaluation, thyroid and kidney function tests, and echography and ophthalmologic assessment [68, 92].

The definition of the hearing threshold level is mandatory since the first evaluation of the child. Audiometric tests are chosen on the basis of patient age [1, 2]. From birth to up to 4 to 6 months, objective tests are preferred: (i) otoacoustic emission (OAE), in association with automatic ABR (auditory brainstem response) in children at risk for hearing loss; (ii) ABR with threshold assessment and, when possible, (iii) ASSR (auditory steady-state responses) evaluation, which can provide useful threshold information among middle frequencies; (iv) tympanometry and acoustic reflex threshold; (v) electrocochleography, in selected cases and when available. From the age of 6 to 7 months, subjective audiometric tests (behavioral tests), such as COR (conditioned orientation reflex) and VRA (visual reinforcement audiometry), can be used with a variable level of reliability. From the age of 2 to 3 years, testing with play audiometry and peep show can be performed; in this period of life, in case of collaborative children and without particular comorbidities, a pure tone laminar audiometry and a vocal audiometry with age-appropriate verbal sets can be tempted [1, 2].

Hearing and Speech Therapy Rehabilitation

Within the first 2 years, neuroplasticity increases rapidly and continues until the age of 3 to 4 years. As a consequence of a cochlear damage during infancy (and, above all, during the first 6 to 8 months), the development of auditory pathways and cortical areas can be impaired [93-95]. If an adequate auditory stimulation is restored (i.e., by hearing aids, to rehabilitate a moderate-severe hearing loss), a reactivation of the neural synaptic connections may be possible, ensuring a regular auditory pathway development [93]. Hence, the early identification of hearing impairment in children and in particular within the first 3 months of life, is really important in order to set the proper and earliest therapeutical-rehabilitative plan [1, 96, 97]. If hearing loss is not recognized and corrected, it has been reported that scholastic learning and social activities may also be compromised, as well as emotional and psychological development [1, 98].

The efficacy of hearing aids is related to their fitting and particularly to the quantity of speech and spectral information transmitted to the central auditory system [99]. Since (i) the earliest diagnosis of hearing disorders, and (ii) the availability innovative technologies (particularly in terms of advanced hearing aids solutions), a progressive improvement of the rehabilitative results achieved in children affected by moderate-severe hearing loss has been observed in the last years [37]. Hearing aids in infancy have been recommended in case of bilateral SNHL, and in case of persistent conductive or mixed hearing loss [1, 96, 100, 101]. Increasing evidences suggest a benefit of hearing aids use also in children with unilateral SNHL[102, 103] and in some cases of auditory neuropathy [104].

A tight audiological follow-up of the hearing-impaired children then allows (i) to fit hearing aids amplification at best, each time, and therefore (ii) to achieve the best verbal perception conditions [1, 105, 106]. Also, a periodic evaluation by speech therapists could help in defining the development of verbal language milestones [1, 2, 107]. Specific attention should be paid to bilingual children, as they are exposed to different language stimuli and have to learn different perceptive characteristics and rules [108, 109].


Hearing loss in children represents a diagnostic and rehabilitative challenge. Its early identification is crucial not only to ensure an adequate language development of children but also to allow the development of their cognitive, relational, social, and even scholastic skills [1, 98, 99, 107]. The diagnostic work-up is often complicated either in order to define the hearing threshold level, either to the identification of the hearing loss etiology, when possible [1, 110]; the latter could indicate, more appropriately and when possible, the best therapeutical-rehabilitative process. For this reason, a stepwise approach to the diagnosis hearing loss during infancy often requires a multidisciplinary team and may involve specialists such as otolaryngologists, audiologists, pediatricians, neonatologists, geneticists, neuroradiologists, and speech therapists [5].

It is otherwise important to remember that not all children with a language disorder present a concomitant hearing defect; sometimes, language skills deterioration may be the sign of a neurological condition, such as an autism spectrum disorder [111]. Also, epileptic encephalopathies, a group of severe cerebral diseases, characterized by epilepsy which may be responsible of a psychomotor regression and, in particular, of a cognitive and communicative impairment should be ruled out [112].

A tight audiological follow-up of children affected by moderate-severe hearing loss is always recommended in order (i) to verify constantly hearing threshold levels as well as the improvement of auditory and perceptive abilities, and (ii) to fit consequently hearing aids at best [1, 105-107].

Peer-review: Externally peer-reviewed.

Author contributions: Concept - A.C., C.A.; Design - A.C., C.A.; Supervision -C.A.; Resource - V.C., L.N.; Materials - C.B., R.T.; Data Collection and/or Processing - L.N., R.T., C.B.; Analysis and/or Interpretation - C.B., A.C.; Literature Search - C.B., V.C.; Writing - V.C., A.C.; Critical Reviews - A.C., C.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.


[1.] American Academy of Pediatrics, Joint Committee on Infant Hearing. Year 2007 position statement: Principles and guidelines for early hearing detection and intervention programs. Pediatrics 2007; 120: 898-921. [CrossRef]

[2.] Harlor AD Jr, Bower C, Committee on Practice and Ambulatory Medicine, Section on Otolaryngology-Head and Neck Surgery. Hearing assessment in infants and children: recommendations beyond neonatal screening. Pediatrics 2009; 124: 1252-63. [CrossRef]

[3.] Rowe A, Gan R, Benton C, Daniel M. Screening for hearing loss in children. J Paediatr Child Health 2016; 26: 26-30. [CrossRef]

[4.] Dimitriou A, Perisanidis C, Chalkiadakis V, Marangoudakis P, Tzagkaroulakis A, Nikolopoulos TP. The universal newborn hearing screening program in a public hospital: The importance of the day of examination. Int J Pediatr Otorhinolaryngol 2016; 91: 90-3. [CrossRef]

[5.] Hart CK, Choo DI. What is the optimal workup for a child with bilateral sensorineural hearing loss? Laryngoscope 2013; 123: 809-10. [CrossRef]

[6.] Fortnum HM, Summerfield AQ, Marshall DH, Davis AC, Bamford JM. Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study. BMJ 2001; 323: 536-40. [CrossRef]

[7.] Minami SB, Mutai H, Nakano A, Arimoto Y, Taiji H, Morimoto N, et al. GJB2-associated hearing loss undetected by hearing screening of newborns. Gene 2013; 532: 41-5. [CrossRef]

[8.] Kennedy C, McCann D, Campbell MJ, Kimm L, Thornton R. Universal newborn screening form permanent childhood hearing impairment: an 8-year follow-up of a controlled trial. Lancet 2005; 366: 660-2. [CrossRef]

[9.] Nunez-Batalla F, Trinidad-Ramos G, Sequi-Canet JM, Alzina De Aguilar V, Jaudenes-Casaubon C. Risk factors for sensorineural hearing loss in children. Acta Otorrinolaringol Esp 2012; 63: 382-90. [CrossRef]

[10.] Kenna MA. Acquired Hearing Loss in Children. Otolaryngol Clin North Am 2015; 48: 933-53. [CrossRef]

[11.] Grindle CR. Pediatric hearing loss. Pediatr Rev 2014; 35: 456-63. [CrossRef]

[12.] Alzahrani M, Tabet P, Saliba I. Pediatric hearing loss: common causes, diagnosis and therapeutic approach. Minerva Pediatr 2015; 67: 75-90.

[13.] Kraft CT, Malhotra S, Boerst A, Thorne MC. Risk indicators for congenital and delayed-onset hearing loss. Otol Neurotol 2014; 35: 1839-43. [CrossRef]

[14.] Lee JW, Pussegoda K, Rassekh SR, Monzon JG, Liu G, Hwang S, et al. Clinical practice recommendations for the management and prevention of ciplastin-induced hearing loss using pharmacogenetic markers. Ther Drug Monit 2016; 38: 423-31. [CrossRef]

[15.] O'Leary CM. Fetal alcohol syndrome: diagnosis, epidemiology, and developmental outcomes. J Pediatr Child Health 2004; 40: 2-7. [CrossRef]

[16.] Jing W, Zongjie H, Denggang F, Na H, Bin Z, Aifen Z, et al. Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis. J Med Genet 2015; 52: 95-103. [CrossRef]

[17.] Cristobal R, Oghalai JS. Hearing loss in children with very low birth weight: current review of epidemiology and pathophysiology. Arch Dis Child Fetal Neonatal 2008; 93: 462-8. [CrossRef]

[18.] Morton CC, Nance WE. Newborn hearing screening - a silent revolution. N Engl J Med 2006; 354: 2151-64. [CrossRef]

[19.] Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. Hearing loss in children with congenital cytomegalovirus infection in relation to the maternal trimester in which the maternal primary infection occurred. Pediatrics 2008; 122: 1123-7. [CrossRef]

[20.] Nassetta L, Kimmberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies. J Antimicrob Chemother 2009; 63: 862-7. [CrossRef]

[21.] Bilavsky E, Shahar-Nissan K, Pardo J, Attias J, Amir J. Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. Arch Dis Child 2016; 101: 433-8. [CrossRef]

[22.] Karltorp E, Hellstrom S, Lewensohn-Fuchs I, Carlsson-Hansen E, Carlsson PI, Engman ML. Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology. Acta Paediatr 2012; 101: e357-62. [CrossRef]

[23.] Boudewyns A, Declau F, Smets K, Ursi D, Eyskens F, Van den Ende J, et al. Cytomegalovirus DNA detection in Guthrie cards: role in the diagnostic work-up of childhood hearing loss. Otol Neurotol 2009; 30: 943-9. [CrossRef]

[24.] Schell A, Kitsko D. Audiometric Outcomes in Pediatric Temporal Bone Trauma. Otolaryngol Head Neck Surg 2016; 154: 175-80. [CrossRef]

[25.] Dunklebarger J, Branstetter B 4th, Lincoln A, Sippey M, Cohen M, Gaines B, et al. Pediatric temporal bone fractures: current trends and comparison of classification schemes. Laryngoscope 2014; 124: 781-4. [CrossRef]

[26.] Declau F, Boudewyns A, Van den Ende J, Peeters A, van den Heyning P. Etiologic and audiologic evaluation after universal neonatal hearing screening: analysis of 170 referred neonates. Pediatrics 2008; 121: 1119-26. [CrossRef]

[27.] Linden Phillips L, Bitner-Glindzicz M, Lench N, Steel KP, Langford C, Daw son SJ, et al. The future role of genetic screening to detect newborns at risk of childhood-onset hearing loss. Int J Audiol 2013; 52: 124-33. [CrossRef]

[28.] Carey JC, Palumbo JC. Advances in the understanding of the genetic causes of hearing loss in children inform a rational approach to evaluation. Indian J Pediatr 2016; 83: 1150-6. [CrossRef]

[29.] Parker M, Bitner-Glindzicz M. Genetic investigations in childhood deafness. Arch Dis Child 2015; 100: 271-8. [CrossRef]

[30.] Avraham KB, Kanaan M. Genomic advances for gene discovery in hereditary hearing loss. J Basic Clin Physiol Pharmacol 2012; 23: 93-7. [CrossRef]

[31.] Chen S, Dong C, Wang Q, Zhong Z, Qi Y, Ke X, et al. Targeted Next-Generation Sequencing Successfully Detects Causative Genes in Chinese Patients with Hereditary Hearing Loss. Genet Test Mol Biomarkers 2016; 20: 660-5. [CrossRef]

[32.] Kim SY, Kim AR, Kim NK, Lee C, Kim MY, Jeon EH, et al. Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not? Medicine (Baltimore) 2016; 95: e3029. [CrossRef]

[33.] Egilmez OK, Kalcioglu MT. Genetics of Nonsyndromic Congenital Hearing Loss. Scientifica (Cairo) 2016; 2016: 7576064.

[34.] Van Camp G, Smith RJH. Hereditary Hearing Loss Homepage; URL: http://hereditary

[35.] Jiang H, Chen J, Shan XJ, Li Y, He JG, Yang BB. Prevalence and range of GJB2 and SLC26A4 mutations in patients with autosomal recessive non-syndromic hearing loss. Mol Med Rep 2014; 10: 379-86. [CrossRef]

[36.] Nance WE. The genetics of deafness. Ment Retard Dev Disabil Res Rev 2003; 9: 109-19. [CrossRef]

[37.] Smith RJ, Bale JF Jr, White KR. Sensorineural hearing loss in children. Lancet 2005; 365: 879-90. [CrossRef]

[38.] Xia W, Liu F, Ma D. Research progress in pathogenic genes of hereditary non-syndromic mid-frequency deafness. Front Med 2016; 10: 137-42. [CrossRef]

[39.] Masoudi M, Ahangari N, Poursadegh Zonouzi AA, Poursadegh Zonouzi A, Nejatizadeh A. Genetic Linkage Analysis of DFNB3, DFNB9 and DFNB21 Loci in GJB2 Negative Families with Autosomal Recessive Non-syndromic Hearing Loss. Iran J Public Health 2016; 45: 680-7.

[40.] Stelma F, Bhutta MF. Non-syndromic hereditary sensorineural hearing loss: review of the genes involved. J Laryngol Otol 2014; 128: 13-21. [CrossRef]

[41.] Chang KW. Genetics of hearing loss - nonsyndromic. Otolaryngol Clin North Am 2015; 48: 1063-72. [CrossRef]

[42.] Mielczarek M, Zakrzewska A, Olszewski J. GJB2 sequencing in deaf and profound sensorineural hearing loss children. Otolaryngol Pol 2016; 70: 21-5. [CrossRef]

[43.] Banjara H, Mungutwar V, Swarnkar N, Patra P. Detection of Connexion 26 GENE (GJB2) Mutations in Cases of Congenital Non Syndromic Deafness. Indian J Otolaryngol Head Neck Surg 2016; 68: 248-53. [CrossRef]

[44.] Wingard JC, Zhao HB. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness. Front Cell Neurosci 2015; 9: 202. [CrossRef]

[45.] Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabedian EN, Petit C. Clinical features of prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet 1999; 353: 1298-303. [CrossRef]

[46.] Cohn ES, Kelley PM. Clinical phenotype and mutations in connexin 26 (DFNB1/GJB2), the most common cause of childhood hearing loss. Am J Med Genet 1999; 89: 130-6. [CrossRef]

[47.] Minami SB, Mutai H, Nakano A, Arimoto Y, Taiji H, Morimoto N, et al. GJB2-associated hearing loss undetected by hearing screening of newborns. Gene 2013; 532: 41-5. [CrossRef]

[48.] Fang Y, Gu M, Wang C, Suo F, Wang G, Xia Y. GJB2 as Well as SLC26A4 Gene Mutations are Prominent Causes for Congenital Deafness. Cell Biochem Biophys 2015; 73: 41-4. [CrossRef]

[49.] Venkatesh MD, Moorchung N, Puri B. Genetics of non syndromic hearing loss. Med J Armed Forces India 2015; 71: 363-8. [CrossRef]

[50.] Stanton SG, Griffin A, Stockley TL, Brown C, Young TL, Benteau T, et al. X-linked hearing loss: two gene mutation examples provide generalizable implications for clinical care. Am J Audiol 2014; 23: 190-200. [CrossRef]

[51.] Groh D, Seeman P, Jilek M, Popelar J, Kabelka Z, Syka J. Hearing function in heterozygous carriers of a pathogenic GJB2 gene mutation. Physiol Res 2013; 62: 323-30.

[52.] Yelverton JC, Arnos K, Xia XJ, Nance WE, Pandya A, Dodson KM. The clinical and audiologic features of hearing loss due to mitochondrial mutations. Otolaryngol Head Neck Surg 2013; 148: 1017-22. [CrossRef]

[53.] Lammens F, Verhaert N, Desloovere C. Syndromic disorders in congenital hearing loss. B-ENT 2013; 21: 45-50

[54.] Bolz HJ. Hereditary Heraing Loss and Its Syndromes Third Edition. Eur J Genet 2016; 24: 1650. [CrossRef]

[55.] Koffler T, Ushakov K, Avraham KB. Genetics of Hearing Loss: Syndromic. Otolaryngol Clin North Am 2015; 48: 1041-61. [CrossRef]

[56.] Huang BY, Zdanski C, Castillo M. Pediatric sensorineural hearing loss, part 2: syndromic and acquired causes. AJNR Am J Neuroradiol 2012; 33: 399-406. [CrossRef]

[57.] Prosser JD, Cohen AP, Greinwald JH. Diagnostic Evaluation of Children with Sensorineural Hearing Loss. Otolaryngol Clin North Am 2015; 48: 975-82. [CrossRef]

[58.] Zazove P, Atcherson SR, Moreland C, McKee MM. Hearing Loss: Diagnosis and Evaluation. FP Essent 2015; 434: 11-7.

[59.] Deklerck AN, Acke FR, Janssens S, De Leenheer EM. Etiological approach in patients with unidentified hearing loss. Int J Pediatr Otorhinolaryngol 2015; 79: 216-22. [CrossRef]

[60.] Forli F, Giuntini G, Bruschini L, Berrettini S. Aetiologic diagnosis of hearing loss in children identified through newborn hearing screening testing. Acta Otorhinolaryngol Ital 2016; 36: 29-37.

[61.] Paludetti G, Conti G, DI Nardo W, DE Corso E, Rolesi R, Picciotti PM, et al. Infant hearing loss: from diagnosis to therapy Official Report of XXI Conference of Italian Society of Pediatric Otorhinolaryngology. Acta Otorhinolaryngol Ital 2012; 32: 347-70.

[62.] Elziere M, Roman S, Nicollas R, Triglia JM. Value of systematic aetiological investigation in children with sensorineural hearing loss. Eur Ann Otorhinolaryngol Head Neck Dis 2012; 129: 185-9. [CrossRef]

[63.] Chen MM, Oghalai JS. Diagnosis and Management of Congenital Sensorineural Hearing Loss. Curr Treat Options Pediatr 2016; 2: 256-65. [CrossRef]

[64.] Tan T, Constantinides H, Mitchell TE. The preauricular sinus: A review of its aetiology, clinical presentation and management. Int J Pediatr Otorhinolaryngol 2005; 69: 1469-74. [CrossRef]

[65.] Kugelman A, Hadad B, Ben-David J, Podoshin L, Borochowitz Z, Bader D. Preauricular tags and pits in the newborn: the role of hearing tests. Acta Paediatr 1997; 86: 170-2. [CrossRef]

[66.] Firat Y, Sireci S, Yakinci C, Akarcay M, Karakas HM, Firat AK, et al. Isolated preauricular pits and tags: is it necessary to investigate renal abnormalities and hearing impairment? Eur Arch Otorhinolaryngol 2008; 265: 1057-60. [CrossRef]

[67.] An SY, Choi HG, Lee JS, Kim JH, Yoo SW, Park B. Analysis of incidence and genetic predisposition of preauricular sinus. Int J Pediatr Otorhinolaryngol 2014; 78: 2255-7. [CrossRef]

[68.] Bitner-Glindzicz M. Hereditary deafness and phenotyping in humans. Br Med Bull 2002; 63: 73-94. [CrossRef]

[69.] Driscoll C, Beswick R, Doherty E, D'Silva R, Cross A. The validity of family history as a risk factor in pediatric hearing loss. Int J Pediatr Otorhinolaryngol 2015; 79: 654-9. [CrossRef]

[70.] Sutton G, Wood S, Feirn R, Minchom S, Parker G, Sirimanna T, Newborn Hearing Screening and Assessment: Guidelines for Surveillance and Audiological Referral of Infants & Children Following the Newborn Hearing Screen 2012. Retrieved from h

[71.] Cohen M, Phillips JA 3rd. Genetic approach to evaluation of hearing loss. Otolaryngol Clin North Am 2012; 45: 25-39. [CrossRef]

[72.] Ma D, Zhang, J, Luo C, Lin Y, Ji X, Hu P, et al. Genetic counselling for patients with nonsyndromic hearing impairment directed by gene analysis. Mol Med Rep 2016; 13: 196-74. [CrossRef]

[73.] Jecmenica J, Bajec-Opancina A, Jecmenica D. Genetic hearing impairment. Childs Nerv Syst 2015; 31: 515-9. [CrossRef]

[74.] Alford RI, Arnos KS, Fox M, Lin JW, Palmer CG, Pandya A, et al. American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss. Genet Med 2014; 16: 347-55. [CrossRef]

[75.] Haffey T, Fowler N, Anne S. Evaluation of unilateral sensorineural hearing loss in the pediatric patient. Int J Pediatr Otorhinolaryngol 2013; 77: 955-8. [CrossRef]

[76.] Dodson KM, Georgolios A, Barr N, Nguyen B, Sismanis A, Arnos KS, et al. Etiology of unilateral hearing loss in a national hereditary deafness repository. Am J Otolaryngol 2012; 33: 590-4. [CrossRef]

[77.] Idan N, Brownstein Z, Shivatzki S, Avraham KB. Advances in genetic diagnostics for hereditary hearing loss. J Basic Clin Physiol Pharmacol 2013; 24: 165-70.

[78.] Sloan-Heggen CM, Smith RJ. Navigating genetic diagnostics in patients with hearing loss. Curr Opin Pediatr 2016; 28: 705-12. [CrossRef]

[79.] Xiong W, Wang D, Gao Y, Gao Y, Wang H, Guan J, et al. Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment. Sci China Life Sci 2015; 58: 829-38. [CrossRef]

[80.] Rodrigues F, Paneque M, Reis C, Venancio M, Sequeiros J, Saraiva J. Non-syndromic sensorineural prelingual deafness: the importance of genetic counseling in demystifying parents' beliefs about the cause of their children's deafness. J Genet Couns 2013; 22: 448-54. [CrossRef]

[81.] Yin A, Liu C, Zhang Y, Wu J, Mai M, Ding H, et al. Genetic counseling and prenatal diagnosis for hereditary hearing loss in high-risk families. Int J Pediatr Otorhinolaryngol 2014; 78: 1356-9. [CrossRef]

[82.] Chen Y, Liu Y, Wang B, Mao J, Wang T, Ye K, et al. Development and validation of a fetal genotyping assay with potential for noninvasive prenatal diagnosis of hereditary hearing loss. Prenat Diagn 2016; 36: 1233-41. [CrossRef]

[83.] Huang BY, Zdanski C, Castillo M. Pediatric sensorineural hearing loss, part 1: practical aspects for neuroradiologists. AJNR Am J Neuroradiol 2012; 33: 211-7. [CrossRef]

[84.] Vaid S, Vaid N. Imaging for cochlear implantation: structuring a clinically relevant report. Clin Radiol 2014; 69: e9-e24. [CrossRef]

[85.] Barath K, Huber AM, Stampfli P, Varga Z, Kollias S. Neuroradiology of cholesteatomas. AJNR Am J Neuroradiol 2011; 32: 221-9. [CrossRef]

[86.] Dougherty W, Kesser BW. Management of Conductive Hearing Loss in Children. Otolaryngol Clin North Am 2015; 48: 955-74. [CrossRef]

[87.] Ross SA, Ahmed A, Palmer AL, Michaels MG, Sanchez PJ, Stewart A, et al. Urine collection method for the diagnosis of congenital Cytomegalovirus infection. Pediatr Infect Dis J 2015; 34: 903-5. [CrossRef]

[88.] Smiechura M, Struzycka M, Konopka W. Congenital and acquired cytomegalovirus infection and hearing evaluation in children. Otolaryngol Pol 2014; 68: 303-7. [CrossRef]

[89.] Harrison GJ. Current controversies in diagnosis, management, and prevention of congenital cytomegalovirus: updates for the pediatric practitioner. Pediatr Ann 2015; 44: e115-25. [CrossRef]

[90.] James SH, Kimberlin DW. Advances in the prevention and treatment of congenital cytomegalovirus infection. Curr Opin Pediatr 2016; 28: 81-5. [CrossRef]

[91.] Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 2003; 143: 16-25. [CrossRef]

[92.] Sanecka A, Biernacka EK, Szperl M, Sosna M, Mueller-Malesinska M, Kozicka U, et al. QTc prolongation in patients with hearing loss: Electrocardiographic and genetic study. Cardiol J 2016: 23: 34-41.


[93.] Bilecen D, Seifritz E, Radu EW, Schmid N, Wetzel S, Probst R, et al. Cortical reorganization after acute unilateral hearing loss traced by fMRI. Neurology 2000; 54: 765-7. [CrossRef]

[94.] Cardon G, Campbell J, Sharma A. Plasticity in the Developing Auditory Cortex: Evidence form Children with sensorineural Hearing Loss and Auditory Neuropathy Spectrum Disorder. J Am Acad Audiol 2012; 23: 396-411. [CrossRef]

[95.] Kral A, O'Donoghue GM. Profound deafness in childhood. N Engl J Med 2010; 363: 1438-50. [CrossRef]

[96.] Walker EA, Holte L, McCreery RW, Spratford M, Page T, Moeller MP. The influence of hearing aid use on outcome of children with mild hearing loss. J Speech Lang Hear Res 2015; 58: 1611-25. [CrossRef]

[97.] Deltenre P, Van Maldergem L. Hearing loss and deafness in the pediatric population: causes, diagnosis, and rehabilitation. Handb Clin Neurol 2013; 113: 1527-38. [CrossRef]

[98.] Vohr B, Topol D, Girard N, St Pierre L, Watson V, Tucker R. Language outcomes and service provision of preschool children with congenital hearing loss. Early Hum Dev 2012; 88: 493-8. [CrossRef]

[99.] Stevenson J, McCann D, Watkin P, Worsfold S, Kennedy C, Hearing Outcomes Study Team. The relationship between language development and behavior problems in children with hearing loss. J Child Psychol Psychiatry 2010; 51: 77-83. [CrossRef]

[100.] Porter H, Sladen DP, Ampah SB, Rothpletz A, Bess FH. Developmental outcomes in early school-age children with minimal hearing loss. Am J Audiol 2013; 22: 263-70. [CrossRef] 101. Gan R, Rowe A, Benton C, Daniel M. Management of hearing loss in children. J Paediatr Child Health 2016; 26: 15-20. [CrossRef]

[102.] McCreery RW, Brennan MA, Hoover B, Kopun J, Stelmachowicz PG. Maximizing audibility and speech recognition with nonlinear frequency compression by estimating audible bandwidth. Ear Hear 2013; 34: e24-7. [CrossRef]

[103.] Paludetti G, Conti G, Di Nardo W, De Corso E, Rolesi R, Picciotti PM, et al. Infant hearing loss: from diagnosis to therapy Official Report of XXI Conference of Italian Society of Pediatric Otorhinolaryngology. Acta Otorhinolaryngol Ital 2012; 32: 347-70.

[104.] Fernandes NF, Yamaguti EH, Morettin M, Costa OA. Speech perception in users of hearing aid with auditory neuropathy spectrum disorder. Codas 2016; 28: 22-6.[CrossRef] 105. Bagatto MP, Moodie ST, Seewald RC, Bartlett DJ, Scollie SD. A critical review of audiological outcome measures for infants and children. Trends Amplif 2011; 15: 23-33. [CrossRef]

[106.] Rissatto MR, Novaes BC. Hearing aids in children: the importance of the verification and validation processes. Pro Fono 2009; 21: 131-6. [CrossRef]

[107.] Joint Committee on Infant Hearing of the American Academy of Pediatrics, Muse C, Harrison J, Yoshinaga-Itano C, Grimes A, Brookhouse PE, Epstein S, et al. Supplement to the JCIH 2007 position statement: principles and guidelines for early intervention after confirmation that a child is deaf on hard of hearing. Pediatrics 2013; 131: 1324-49. [CrossRef]

[108.] Bunta F, Douglas M. The effects of dual-language support on the language skills of bilingual children with hearing loss who use listening devices relative to their monolingual peers. Lang Speech Hear Serv Sch 2013; 44: 281-90. [CrossRef]

[109.] Crowe K, McKinnon DH, McLeod S, Ching TY. Multilingual children with hearing loss: Factors contributing to language use at home and in early education. Child Lang Teach Ther 2013; 29: 111-29. [CrossRef]

[110.] Liming BJ, Carter J, Cheng A, Choo D, Curotta J, Carvalho D, et al. International Pediatri Otolaryngology Group (IPOG) consensus recommendations: hearing loss in the pediatric patient. Int J Pediatr Otorhinolaryngol 2016; 90: 251-8. [CrossRef]

[111.] Machado FP, Palladino RR, Damasceno LL, Cunha MC. Appropriateness of Using Autism Spectrum Disorders Screening Tools in a Hearing Evaluation Service. Folia Phoniatr Logop 2016; 68: 60-6. [CrossRef]

[112.] Shao LR, Stafstrom CE. Pediatric Epileptic Encephalopathies: Pathophysiology and Animal Models. Semin Pediatr Neurol 2016; 23: 98-107. [CrossRef]

Andrea Ciorba, Virginia Corazzi, Laura Negossi, Rita Tazzari, Chiara Bianchini, Claudia Aimoni

Department of Ear, Nose and Throat and Audiology, University Hospital of Ferrara, Ferrara, Italy

ORCID IDs of the authors: C.A. 0000-0003-3455-2295; C.V. 0000-0002-3189-6247

Cite this article as: Ciorba A, Corazzi V, Negossi L, Tazzari R, Bianchini C, Aimoni C. Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge. J Int Adv Otol 2017; 13: 407-13.

Corresponding Address: Andrea Ciorba E-mail:

Submitted: 16.07.2017 * Revision Received: 04.09.2017 * Accepted: 19.11.2017

DOI: 10.5152/iao.2017.4162
Table 1. Literature evaluation and selection, according to PRISMA
criteria (

Total number of articles obtained by PubMed, Embase, and  617
Cinahl search
Other papers from references in the published literature   26
Total number of papers identified                         643
Paper excluded (1)                                        479
Article assessed for eligibility                          146
Paper excluded (2)                                         60
Total number of papers finally identified                  86

(1) Inclusion criteria were: clinical series, review papers. Exclusion
criteria were: not availability of a full text; manuscripts not in the
English language; case reports.
(2) Inclusion criteria were: for clinical series, papers with an
adequate group of patients studied (n>20); for reviews, papers
published on relevant journals and papers showing a rigorous methods
and rigorous reporting.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

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Author:Ciorba, Andrea; Corazzi, Virginia; Negossi, Laura; Tazzari, Rita; Bianchini, Chiara; Aimoni, Claudia
Publication:The Journal of the International Advanced Otology
Date:Dec 1, 2017
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