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Genetic Hearing Loss

Editor: Matthew Ng Updated: 4/17/2023 4:25:37 PM


Hearing loss is the impairment of auditory function, which can have significant long-term consequences on social and language development. It can develop prelingually (before the acquisition of speech/language) or post-lingually (after the acquisition of speech/language). Hearing loss can be classified as conductive hearing loss (CHL), caused by the reduction of sound transmission through the external or middle ear to the inner ear, and sensorineural hearing loss (SNHL), which is caused by dysfunction of the inner ear or auditory nerve. Mixed hearing loss features both a conductive and sensorineural component. Sensorineural hearing losses can be categorized into acquired (e.g., noise-induced) and inherited (e.g., genetic). This article will focus on the genetic mechanisms, diagnosis, and management of genetic SNHL.[1]


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Genetic hearing loss accounts for 50% of all cases of hearing loss.  The remainder is due to acquired causes such as infection, trauma, noise exposure, and ototoxicity.

Inherited genetic hearing loss can be categorized as part of a syndrome (30% of inherited hearing loss) and non-syndromic (70% of inherited hearing loss). For non-syndromic hearing loss, autosomal recessive is the most common inherited form, accounting for 75 to 80% of cases. Autosomal dominant comprises approximately 20%. X-linked, Y-linked, and mitochondrial-inherited comprise the remaining 5%.[2]


Hearing loss is the most common sensory system disorder, with 1 in 1,000 children born with hearing impairment. The prevalence of SNHL continues to increase throughout childhood, reaching 2.7 per 1000 children by age 5. Currently, it is estimated that 300 million people suffer from hearing loss.[3]


Non-Syndromic Hearing Loss

Non-syndromic hearing loss accounts for the majority of hereditary hearing loss, with over 70 loci identified in its pathogenesis.[4] Each locus is identified with a specialized nomenclature. The prefix DFN (used to refer to deafness) is given to each gene locus and followed by either A for autosomal dominant or B for autosomal recessive inheritance. A number then follows the name to illustrate the order in which the gene was discovered. For example, DFNB1 is a locus responsible for non-syndromic hearing loss inherited in an autosomal recessive fashion and was the first locus to be identified. While many gene loci candidates have been identified, there are still more yet to be discovered, and the precise cause of many cases of non-syndromic deafness remains unknown.[4]

  • Autosomal recessive SNHL, where a mutation in both alleles is required to cause disease phenotype, is the most common form of non-syndrome hearing loss accounting for 75 to 80% of cases. Autosomal recessive deafness tends to be prelingual in onset, constant in nature, and severe.[5][6] To date, 71 loci have been identified as causing autosomal recessive non-syndromic hearing loss.[4] The protein products of these genes include ion channels, membrane proteins, transcription factors, and various cytoskeletal elements.
    • Connexin 26 (DFNB1) is the most common non-syndrome autosomal recessive locus, accounting for 30 to 40% of all cases of deafness.[7][8][9] Connexins are transmembrane proteins that play a role in intercellular signaling via gap junctions.
  • Autosomal dominant SNHL only requires one allele to be mutated to cause the disease phenotype. It tends to be post-lingual in onset, progressive, and milder.[5][6] To date, 54 loci have been identified which cause autosomal dominant non-syndromic hearing loss.
  • X-linked inheritance acts as a recessive trait in females who require mutations in both X alleles to cause disease phenotype. However, since males only have one X-chromosome, it behaves more as a dominant trait and manifests at a disproportionally higher rate in men than women. Five loci and three genes have been mapped for the X-linked form.
  • Mitochondrial disorders are inherited via mutations of the mitochondrial DNA and are only passed from mother to child. Seven loci and several gene point mutations have been identified for the mitochondrial form. The A1555G mutation in 12S rRNA is believed to predispose to aminoglycoside-induced deafness in addition to non-syndromic hearing loss.[10][11]

Syndromic Hearing Loss

Syndrome hearing loss is associated with a constellation of other clinical deficiencies and organ system involvement. There are over 400 syndromes associated with hearing loss. Thus, the diagnosis of hearing impairment in a child should prompt a thorough investigation to rule out a syndromic disorder. The severity of hearing loss can vary across different syndromes, ranging from mild impairment to profound loss. Similar to non-syndromic deafness, syndromic hearing loss can also be inherited in an autosomal recessive, autosomal dominant, X-linked, and mitochondrial fashion.

Autosomal Recessive Syndromic Hearing Loss

  • Pendred Syndrome is the most cause of syndromic hearing loss, accounting for 10% of all cases of hereditary hearing loss. Pendred syndrome is caused by a mutation in the gene SLC26A4, which codes for the protein pendrin, an anion transporter. Patients present with SNHL, bilateral enlarged vestibular aqueducts or Mondini dysplasia, and euthyroid goiter.[12]
  • Usher syndromes are a common cause of autosomal recessive syndromic hearing loss and the most common syndrome affecting both hearing and vision, accounting for 50% of all deafness-blindness cases.[13] There are three subtypes of Usher syndrome: USH1, USH2, and USH3. Each has varying degrees of hearing loss, vestibular dysfunction, and retinitis pigmentosa.[13]
    • USH1 has profound bilateral deafness and severe vestibular dysfunction at birth. Retinitis pigmentosa becomes apparent before age 10.
    • USH2 has moderate to severe hearing loss at birth with normal vestibular function and retinitis pigmentosa that manifests later in the teenage years.
    • USH3 has normal to near normal vestibular function and progressive hearing loss. Retinitis pigmentosa manifests later in the teenage years.[14]
  • Jervell and Lange-Nielsen syndrome (JLNS) has SNHL and prolonged QTc intervals (>500 ms). There is a predisposition for syncope from ventricular tachyarrhythmias, most notably torsades de pointes. A similar syndrome, Romano-Ward syndrome, lacks SNHL. The genetic cause of JLNS is due to genes KCNQ1 and KCNE1, which encode subunits of potassium channels in cardiac and auditory tissue. Thus, children diagnosed with sensorineural hearing loss should also be screened with an EKG to assess for prolonged QTC intervals.
  • Miller syndrome is very rare at 1 per 1,000,000 live births. It is characterized by craniofacial anomalies, limb anomalies, and conductive hearing loss due to middle ear abnormalities.[15]
  • Nager syndrome consists of facial and limb malformations, ear anomalies, and sensorineural hearing loss.[16]

Autosomal Dominant Syndromic Hearing Loss

  • Branchio-oto-renal (BOR) syndrome has a constellation of branchial arch, otologic, and renal defects and affects about 2% of profound hearing loss in children. BOR can cause sensorineural, conductive, or mixed hearing and can cause abnormalities in the external, middle, or inner ear. Patents can have preauricular pits, microtia, ossicular malformation, or cochlear hypoplasia.[17] Branchial arch anomalies include fistulae, pits, or sinuses, while renal abnormalities can range from renal hypoplasia to complete agenesis. There are three different genes – EYA1 and two additional genes, SIX1 and SIX5, responsible for BOR syndrome.
  • Waardenburg syndrome has an incidence of 1 in 40,000 live births and consists of SNHL and abnormal pigmentation of the eyes, skin, and hair. Patients can have the classic “white forelock” and iris heterochromia.[18] There are four subtypes of Waardenburg syndrome with slight variations in clinical features and different gene mutations.
  • Goldenhar syndrome (hemifacial microsomia) is predominantly inherited sporadically, although rarely, it can present in an autosomal dominant manner. It has an incidence of 1 per 5000 to 25000 live births and presents with anomalies of the face and ears with hearing loss encompassing both conductive and sensorineural ranging from mild to severe.
  • CHARGE syndrome has an incidence of 1 in 8,500 to 10,000 live births and is defined by coloboma, hearing anomalies, atresia choanalis, stunted growth, genitourinary malformations, and anomalies of the ear. Hearing impairment can occur from a range of anomalies, including stenotic external auditory canal, Mondini dysplasia, hypoplasia, agenesis of the auditory nerve, ossicular chain anomaly, and absence of middle ear structures.[19]
  • Stickler syndrome has an incidence of 1 in 7,500 to 9,000 live births and is most commonly due to mutations in the COL2A gene responsible for type II collagen formation. It is characterized by flattened facies, myopia, cleft palate, macroglossia, arthritis, scoliosis, and mitral valve prolapse. Hearing loss can be conductive due to stapes fixation or sensorineural due to collagen defect in the organ of Corti.[20]
  • Treacher Collins has an incidence of 1 per 50,000 live births and has abnormalities of the face, eyes, and ears. 40 to 50% of children have conductive hearing loss or high-frequency sensorineural hearing loss.[21] 
  • Apert syndrome occurs in 1 in 65,000 to 88,000 live births and is characterized by craniosynostosis, frontal bossing, syndactyly, and vision and hearing impairment. Patients often have bilateral conductive hearing loss from middle ear effusions or ossicular chain fixation. Sensorineural hearing loss can occur from cochlear dysplasia.[22]
  • Crouzon has an incidence of 1 in 50,000 live births with craniosynostosis, high forehead, lagophthalmos, and hearing impairment. 30% of patients have conductive hearing loss from external ear malformations, middle ear effusions, ossicular chain dysplasia, and oval window anomalies. Sensorineural hearing loss is rarely seen.[23]
  • Saethre-Chotzen syndrome has an incidence of 1 in 250,000 to 500,000 live births with brachycephaly, vertebrae anomalies, and short statures. Hearing loss is usually conductive with anomalies of the external auditory canal, stapes ankylosis, ossicular chain fixation, and middle cavity anomalies.[24]
  • Townes-Brocks syndrome has an incidence of 1 in 250,000 with anus imperforatus, external ear anomalies, and thumb anomalies.

X-Linked Recessive Syndromic Hearing Loss

  • Alport syndrome is secondary to anomalies in type IV collagen resulting in SNHL, nephritis, and ocular defects. Since type IV collagen is a significant component of the basement membrane, its mutation can lead to hematuria from glomerular basement membrane involvement. Ocular manifestations include anterior lenticonus, perimacular flecks, and corneal lesions. It is predominantly inherited in an X-linked recessive manner via gene COL4A5, which encodes the a5 chain of type IV collagen.[25] However, mutations in COL4A3 and COL4A4, which encode a3 and a4 chains, are also implicated in the pathogenesis of Alport syndrome but are transmitted by autosomal recessive inheritance
  • Mohr-Tranebjaerg syndrome presents with post-lingual SNHL, dystonia, spasticity, dysphagia, and optic atrophy. It is similar to Friedreich’s ataxia without cardiomyopathy.
  • Mitochondrial-Inherited syndromic hearing loss often presents with bilateral, high-frequency hearing loss. Syndromes include MELAS syndrome (mitochondria encephalopathy, lactic acidosis, and stroke-like episodes), Kearns-Sayre syndrome, and MERRF (myoclonic epilepsy with ragged red fibers).

History and Physical

Children with hearing loss should undergo a complete clinical history, including perinatal details to help identify any environmental influences such as intrauterine infections, trauma, medications, and other medical conditions during pregnancy. A thorough family history should be obtained to assess for any genetic history of hearing loss. The results of newborn hearing screening testing should be ascertained.

A physical exam for childhood hearing loss should include a complete head-to-toe exam to assess for any syndromic features. Key organ systems commonly associated with hearing loss include ophthalmologic, endocrine, renal, and cardiac systems.


Newborn hearing screening: The universal newborn hearing screening program (UNHS) has significantly improved the diagnosis of childhood hearing loss and reduced the average age of diagnosis from 24-30 months to 2-3 months. The screening utilizes an otoacoustic emissions (OAE) test, and children who fail will undergo a repeat test in several weeks. If the child continues to fail the hearing tests, auditory brainstem evoked (ABR) testing is required to confirm the hearing loss. The use of evoked otoacoustic emissions and auditory brainstem response testing has substantially increased the number of children identified to have hearing loss and reduced the number of infants falsely identified as having a hearing impairment.[26]

Genetic testing: 50% of all childhood hearing loss and 66% of prelingual hearing loss result from genetic causes. Current hearing screening programs can only detect hearing loss beyond 35 dB. Thus, genetic screening can help identify children with mild SNHL that are missed with conventional screening. Clinicians should aim to answer three key questions: is there an environmental cause? Is there a constellation of signs and clinical features to suggest a syndrome? Is there a family history with similar patterns of onset and type of hearing loss?

After ruling out environmental causes, genetic mutation testing for DFNB1 in the gene GJB2 is recommended as it is the most common cause of non-syndrome hearing loss. For children in whom syndromic hearing loss is suspected, gene-specific mutation screening should be performed to confirm the syndrome. Genetic screening for mitochondrial A1555G can also help minimize hearing loss by protecting them against aminoglycoside antibiotics. Additionally, genetic tests will depend on the pedigree constructed by the medical geneticist. It is important to note that a negative genetic test does not rule out a genetic cause for hearing loss.[27][28]

Computed tomography (CT): CT scans can be used to visualize the temporal bones, mastoid, otic capsule, and middle ear for any anatomical anomalies responsible for hearing loss. One of the most common CT findings of SNHL is Mondini dysplasia, which is the hypoplasia of the cochlear basal turn, leading to progressive SNHL. In cases of dilated vestibular aqueducts, genetic screening for Pendred syndrome is warranted.[29]

Magnetic resonance imaging (MRI): Nuclear MRI with high resolution can detect deformities of the membranous labyrinth, internal auditory canal, and cerebellopontine angle. Scheibe dysplasia or cochleosaccular dysplasia affects the pars inferior. Alexander malformation affects the cochlear duct and the basal turn of the cochlear, leading to high-frequency hearing loss. MR imaging is also useful to identify any cochlear nerve dysplasia or aplasia that might be responsible for sensorineural hearing loss.[29][30]

Electrocardiogram: It is recommended due to the remote possibility of Jervell and Lange-Nielsen syndrome.

Treatment / Management

Treatments for significant hearing loss include hearing aids, cochlear implants, and implantable bone-conduction devices. 

Conventional hearing aids are electronic devices that amplify sound to the ears. Generally, they are beneficial for patients with mild to severe sensorineural hearing loss with good to excellent speech recognition ability and hearing clarity. Hearing aids come in three different styles: behind the ear (BTE), in the ear (ITE), and canal types (either in the canal (ITC) or completely in the canal (CIC). Most children are fit with BTE hearing aids which facilitates long-term use as the hearing aid molds can be readily fashioned for the growing child while keeping the same hearing aid housing. The non-BTE hearing aids provide the advantage of being less visible. 

Patients with severe to profound hearing loss with minimal to no benefit from hearing aids are candidates for cochlear implantation. A cochlear implant is an internally implantable electronic device that works in conjunction with an externally worn sound processor that stimulates the afferent fibers of the auditory nerve with electrical current. Although they do not replace acoustic hearing, they can provide access to a wider frequency range and improve speech understanding with habilitation and practice.[31][32](B3)

Cochlear implants in children born with deafness have been shown to significantly benefit speech and language development, with earlier younger implantation leading to greater vocabulary. The best cochlear implant results are obtained in post-lingual deafness and those with early-identified deafness (younger than the age of 2 years ) with early cochlear implant intervention. The FDA has now approved cochlear implantation for infants as young as 9-months old who meet the criteria. Cochlear implantation has been found to be effective in CHARGE syndrome, Jervell, and Lange-Neilsen syndrome, Waardenburg syndrome, Usher syndrome, and Pendred syndrome.[33][34][35](B2)

Implantable bone-conduction hearing devices are utilized for patients with conductive hearing loss, mixed hearing loss, or single-sided hearing loss. The external and middle ear are bypassed, with sound being transmitted to the cochlea via bone conduction. Bone conduction devices are either percutaneous (skin-penetrating) or transcutaneous (implanted under the scalp). Bone-conduction devices can be particularly beneficial in patients with anatomic abnormalities of the external or middle ears not amenable to reconstructive ear surgery. Bone conduction devices have demonstrated effectiveness for patients with Treacher Collins, BOR, Nager, and Goldenhar syndromes.[36][37]

Differential Diagnosis

The differential diagnosis of hearing loss should include all genetic and acquired causes. Aside from genetic causes, as previously mentioned, other congenital forms can be caused by prenatal infections, anatomic malformations, and ototoxic medications.

Treatment Planning

Because of the variable genetic mechanisms of sensorineural hearing loss, the best prevention is achievable by appropriately screening potential parents with familial history of hearing loss.  As discussed, autosomal recessive forms of hearing loss are generally from asymptomatic parents, thus, a thorough genetic screening of couples with a history of familial hereditary hearing impairment is warranted.

The timing of initiation of rehabilitation is also critical. Hearing amplification should be instituted as soon as possible. The Joint Committee on Infant Hearing recommended in 2007 the initiation of rehabilitation no later than six months of age to minimize the impact on language development.[38] Studies have also documented that earlier cochlear implantation (under 18 months) results in markedly improved performance than children implanted later in life.[39]


Genetic SNHL can have significant social, economic, and medical repercussions. Prognosis is dependent on the etiology and can be improved with early diagnosis and intervention.[39] The longer the time from diagnosis to intervention, the poorer the speech and language outcomes will become, as well as poorer cognitive development. [40] Simultaneous exposure to more than one spoken language in the home is also associated with worse outcomes.[41]

As advancements are made in genetic testing and therapy, there will continue to be an improvement in the diagnosis of syndromic hearing loss with the potential for restoring hearing function in patients with certain syndromes.[42][43]


Delayed diagnosis and treatment of hearing loss can have lifelong consequences on verbal and spoken-language communication and social development. Children can suffer speech delay, impaired communication with their peers, social withdrawal, decreased self-esteem, and fewer educational and job opportunities.


Due to the multifactorial nature of hearing loss, the evaluation of a child with significant hearing loss should ideally take place by a multidisciplinary team involving geneticists, audiologists, otolaryngologists, pediatricians, speech and language pathologists, psychologists, early childhood special needs educators, social workers, and any other medical professionals depending on any syndromic findings.

Because many deaf infants are born to non-deaf parents, it is crucial to ensure accurate and updated information is delivered by the most qualified health care professional to parents. It is advisable to consult a medical geneticist who can accurately relay recurrence risk to the parents in these circumstances.

Deterrence and Patient Education

Since most prelingually deaf children are born to hearing parents, oral/verbal communication is usually preferred over visual sign-language communications. However, some parents favor signing because they are either deaf themselves or wish to preserve the communication culture of the deaf community. Clinicians should be aware of this dynamic but also provide patients and their families with all the information regarding assistive hearing devices.  

Parents will need to be informed of the treatment options and given realistic expectations of hearing improvement. Depending on the etiology of hearing loss, the timing of diagnosis, and selected treatments, hearing outcomes can vary substantially. Parents should be encouraged to maintain a key role in their children’s rehabilitation and be guided on the financial implications of their local health insurance system.[41] Access to rehabilitation services is expensive and can hinder optimal remediation even in developed countries.

Enhancing Healthcare Team Outcomes

Patients diagnosed with hearing loss should be managed by a multidisciplinary team of otolaryngologists, audiologists, speech-language pathologists, pediatricians, and primary care physicians. Children with suspected hearing loss should be immediately referred for proper hearing screening, genetic testing, and hearing augmentation with hearing assistive devices and/or speech rehabilitation to promote long-term speech and language outcomes.

Long-term monitoring of childhood development should be undertaken by the pediatrician by regular follow-up with audiology for routine hearing aid and audiogram assessments. Formal peer support groups with hearing loss can aid children and parents in addressing their concerns. The school system should also provide an optimal learning environment in the classroom for children with hearing impairments.



Liang B, Huang H, Zhang J, Chen G, Kong X, Zhu M, Wang P, Tang L. Case Report: Chanarin-Dorfman Syndrome: A Novel Homozygous Mutation in ABHD5 Gene in a Chinese Case and Genotype-Phenotype Correlation Analysis. Frontiers in genetics. 2022:13():847321. doi: 10.3389/fgene.2022.847321. Epub 2022 Mar 28     [PubMed PMID: 35419035]

Level 3 (low-level) evidence


Morikawa S, Blacher L, Onwumere C, Urano F. Loss of Function of WFS1 Causes ER Stress-Mediated Inflammation in Pancreatic Beta-Cells. Frontiers in endocrinology. 2022:13():849204. doi: 10.3389/fendo.2022.849204. Epub 2022 Mar 25     [PubMed PMID: 35399956]


Hu Y, Lauffer P, Stewart M, Codner G, Mayerl S, Heuer H, Ng L, Forrest D, van Trotsenburg P, Jongejan A, Fliers E, Hennekam R, Boelen A. An animal model for Pierpont syndrome: a mouse bearing the Tbl1xr1Y446C/Y446C mutation. Human molecular genetics. 2022 Aug 25:31(17):2951-2963. doi: 10.1093/hmg/ddac086. Epub     [PubMed PMID: 35416977]

Level 3 (low-level) evidence


Schrijver I. Hereditary non-syndromic sensorineural hearing loss: transforming silence to sound. The Journal of molecular diagnostics : JMD. 2004 Nov:6(4):275-84     [PubMed PMID: 15507665]


Van Camp G, Willems PJ, Smith RJ. Nonsyndromic hearing impairment: unparalleled heterogeneity. American journal of human genetics. 1997 Apr:60(4):758-64     [PubMed PMID: 9106521]


Hildebrand MS, Kahrizi K, Bromhead CJ, Shearer AE, Webster JA, Khodaei H, Abtahi R, Bazazzadegan N, Babanejad M, Nikzat N, Kimberling WJ, Stephan D, Huygen PL, Bahlo M, Smith RJ, Najmabadi H. Mutations in TMC1 are a common cause of DFNB7/11 hearing loss in the Iranian population. The Annals of otology, rhinology, and laryngology. 2010 Dec:119(12):830-5     [PubMed PMID: 21250555]


Zelante L, Gasparini P, Estivill X, Melchionda S, D'Agruma L, Govea N, Milá M, Monica MD, Lutfi J, Shohat M, Mansfield E, Delgrosso K, Rappaport E, Surrey S, Fortina P. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Human molecular genetics. 1997 Sep:6(9):1605-9     [PubMed PMID: 9285800]


Denoyelle F, Marlin S, Weil D, Moatti L, Chauvin P, Garabédian EN, Petit C. Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling. Lancet (London, England). 1999 Apr 17:353(9161):1298-303     [PubMed PMID: 10218527]

Level 2 (mid-level) evidence


Dodson KM, Blanton SH, Welch KO, Norris VW, Nuzzo RL, Wegelin JA, Marin RS, Nance WE, Pandya A, Arnos KS. Vestibular dysfunction in DFNB1 deafness. American journal of medical genetics. Part A. 2011 May:155A(5):993-1000. doi: 10.1002/ajmg.a.33828. Epub 2011 Apr 4     [PubMed PMID: 21465647]

Level 2 (mid-level) evidence


Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature genetics. 1993 Jul:4(3):289-94     [PubMed PMID: 7689389]

Level 2 (mid-level) evidence


Estivill X, Govea N, Barceló E, Badenas C, Romero E, Moral L, Scozzri R, D'Urbano L, Zeviani M, Torroni A. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides. American journal of human genetics. 1998 Jan:62(1):27-35     [PubMed PMID: 9490575]


Dror AA, Brownstein Z, Avraham KB. Integration of human and mouse genetics reveals pendrin function in hearing and deafness. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2011:28(3):535-44. doi: 10.1159/000335163. Epub 2011 Nov 18     [PubMed PMID: 22116368]

Level 3 (low-level) evidence


Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches. Current opinion in neurology. 2012 Feb:25(1):42-9. doi: 10.1097/WCO.0b013e32834ef8b2. Epub     [PubMed PMID: 22185901]

Level 3 (low-level) evidence


Bonnet C, Grati M, Marlin S, Levilliers J, Hardelin JP, Parodi M, Niasme-Grare M, Zelenika D, Délépine M, Feldmann D, Jonard L, El-Amraoui A, Weil D, Delobel B, Vincent C, Dollfus H, Eliot MM, David A, Calais C, Vigneron J, Montaut-Verient B, Bonneau D, Dubin J, Thauvin C, Duvillard A, Francannet C, Mom T, Lacombe D, Duriez F, Drouin-Garraud V, Thuillier-Obstoy MF, Sigaudy S, Frances AM, Collignon P, Challe G, Couderc R, Lathrop M, Sahel JA, Weissenbach J, Petit C, Denoyelle F. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. Orphanet journal of rare diseases. 2011 May 11:6():21. doi: 10.1186/1750-1172-6-21. Epub 2011 May 11     [PubMed PMID: 21569298]

Level 2 (mid-level) evidence


Delb W, Lipfert S, Henn W. Mandibulofacial dysostosis, microcephaly and thorax deformities in two brothers: a new recessive syndrome? Clinical dysmorphology. 2001 Apr:10(2):105-9     [PubMed PMID: 11310989]

Level 3 (low-level) evidence


Herrmann BW, Karzon R, Molter DW. Otologic and audiologic features of Nager acrofacial dysostosis. International journal of pediatric otorhinolaryngology. 2005 Aug:69(8):1053-9     [PubMed PMID: 16005346]

Level 2 (mid-level) evidence


Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM Jr, Brophy PD, Berkman J, Gattas M, Hyland V, Ruf EM, Schwartz C, Chang EH, Smith RJ, Stratakis CA, Weil D, Petit C, Hildebrandt F. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proceedings of the National Academy of Sciences of the United States of America. 2004 May 25:101(21):8090-5     [PubMed PMID: 15141091]


Zhang H, Chen H, Luo H, An J, Sun L, Mei L, He C, Jiang L, Jiang W, Xia K, Li JD, Feng Y. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II. Human genetics. 2012 Mar:131(3):491-503. doi: 10.1007/s00439-011-1098-2. Epub 2011 Oct 1     [PubMed PMID: 21965087]

Level 3 (low-level) evidence


Blake KD, Prasad C. CHARGE syndrome. Orphanet journal of rare diseases. 2006 Sep 7:1():34     [PubMed PMID: 16959034]


Nowak CB. Genetics and hearing loss: a review of Stickler syndrome. Journal of communication disorders. 1998 Sep-Oct:31(5):437-53; 453-4     [PubMed PMID: 9777489]


Marszałek-Kruk BA, Wójcicki P, Dowgierd K, Śmigiel R. Treacher Collins Syndrome: Genetics, Clinical Features and Management. Genes. 2021 Sep 9:12(9):. doi: 10.3390/genes12091392. Epub 2021 Sep 9     [PubMed PMID: 34573374]


Huang F, Sweet R, Tewfik TL. Apert syndrome and hearing loss with ear anomalies: a case report and literature review. International journal of pediatric otorhinolaryngology. 2004 Apr:68(4):495-501     [PubMed PMID: 15013619]

Level 3 (low-level) evidence


Agochukwu NB, Solomon BD, Muenke M. Hearing loss in syndromic craniosynostoses: introduction and consideration of mechanisms. American journal of audiology. 2014 Jun:23(2):135-41. doi: 10.1044/2014_AJA-13-0036. Epub     [PubMed PMID: 24686979]

Level 3 (low-level) evidence


Lee S, Seto M, Sie K, Cunningham M. A child with Saethre-Chotzen syndrome, sensorineural hearing loss, and a TWIST mutation. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. 2002 Jan:39(1):110-4     [PubMed PMID: 11772178]

Level 3 (low-level) evidence


Artuso R, Fallerini C, Dosa L, Scionti F, Clementi M, Garosi G, Massella L, Epistolato MC, Mancini R, Mari F, Longo I, Ariani F, Renieri A, Bruttini M. Advances in Alport syndrome diagnosis using next-generation sequencing. European journal of human genetics : EJHG. 2012 Jan:20(1):50-7. doi: 10.1038/ejhg.2011.164. Epub 2011 Sep 7     [PubMed PMID: 21897443]

Level 3 (low-level) evidence


Norton SJ, Gorga MP, Widen JE, Folsom RC, Sininger Y, Cone-Wesson B, Vohr BR, Fletcher KA. Identification of neonatal hearing impairment: a multicenter investigation. Ear and hearing. 2000 Oct:21(5):348-56     [PubMed PMID: 11059697]


Wu CC, Hung CC, Lin SY, Hsieh WS, Tsao PN, Lee CN, Su YN, Hsu CJ. Newborn genetic screening for hearing impairment: a preliminary study at a tertiary center. PloS one. 2011:6(7):e22314. doi: 10.1371/journal.pone.0022314. Epub 2011 Jul 19     [PubMed PMID: 21811586]


Linden Phillips L, Bitner-Glindzicz M, Lench N, Steel KP, Langford C, Dawson SJ, Davis A, Simpson S, Packer C. The future role of genetic screening to detect newborns at risk of childhood-onset hearing loss. International journal of audiology. 2013 Feb:52(2):124-33. doi: 10.3109/14992027.2012.733424. Epub 2012 Nov 7     [PubMed PMID: 23131088]


Yu F, Han DY, Dai P, Kang DY, Zhang X, Liu X, Zhu QW, Yuan YY, Sun Q, Xue DD, Li M, Liu J, Yuan HJ, Yang WY. [Mutation of GJB2 gene in nonsyndromic hearing impairment patients: analysis of 1190 cases]. Zhonghua yi xue za zhi. 2007 Oct 30:87(40):2814-9     [PubMed PMID: 18167282]

Level 3 (low-level) evidence


Orzan E, Murgia A. Connexin 26 deafness is not always congenital. International journal of pediatric otorhinolaryngology. 2007 Mar:71(3):501-7     [PubMed PMID: 17222463]


Casazza G, Meier JD. Evaluation and management of syndromic congenital hearing loss. Current opinion in otolaryngology & head and neck surgery. 2017 Oct:25(5):378-384. doi: 10.1097/MOO.0000000000000397. Epub     [PubMed PMID: 28697000]

Level 3 (low-level) evidence


Rah YC, Lee JY, Suh MW, Park MK, Lee JH, Chang SO, Oh SH. Cochlear Implantation in Patients With CHARGE Syndrome. The Annals of otology, rhinology, and laryngology. 2016 Nov:125(11):924-930     [PubMed PMID: 27557911]


van Nierop JW, Huinck WJ, Pennings RJ, Admiraal RJ, Mylanus EA, Kunst HP. Patients with Pendred syndrome: is cochlear implantation beneficial? Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2016 Aug:41(4):386-94. doi: 10.1111/coa.12532. Epub 2016 Feb 8     [PubMed PMID: 26331303]


Eftekharian A, Mahani MH. Jervell and Lange-Nielsen syndrome in cochlear implanted patients: our experience and a review of literature. International journal of pediatric otorhinolaryngology. 2015 Sep:79(9):1544-7. doi: 10.1016/j.ijporl.2015.07.012. Epub 2015 Jul 14     [PubMed PMID: 26205899]


Pradhananga RB, Thomas JK, Natarajan K, Kameswaran M. Long term outcome of cochlear implantation in five children with common cavity deformity. International journal of pediatric otorhinolaryngology. 2015 May:79(5):685-9. doi: 10.1016/j.ijporl.2015.02.015. Epub 2015 Feb 24     [PubMed PMID: 25758199]

Level 2 (mid-level) evidence


Rosa F, Coutinho MB, Ferreira JP, Sousa CA. Ear malformations, hearing loss and hearing rehabilitation in children with Treacher Collins syndrome. Acta otorrinolaringologica espanola. 2016 May-Jun:67(3):142-7. doi: 10.1016/j.otorri.2015.01.005. Epub 2015 May 27     [PubMed PMID: 26025357]


Oliveira AK, Ferro LP, da Silva JN, Okada DM. Results of the implantation of bone-anchored hearing aids in patients with treacher-collins syndrome. International archives of otorhinolaryngology. 2013 Apr:17(2):222-6. doi: 10.7162/S1809-97772013000200018. Epub     [PubMed PMID: 25992018]


Joint Committee on Infant Hearing of the American Academy of Pediatrics, Muse C, Harrison J, Yoshinaga-Itano C, Grimes A, Brookhouser PE, Epstein S, Buchman C, Mehl A, Vohr B, Moeller MP, Martin P, Benedict BS, Scoggins B, Crace J, King M, Sette A, Martin B. Supplement to the JCIH 2007 position statement: principles and guidelines for early intervention after confirmation that a child is deaf or hard of hearing. Pediatrics. 2013 Apr:131(4):e1324-49. doi: 10.1542/peds.2013-0008. Epub 2013 Mar 25     [PubMed PMID: 23530178]


Kral A, O'Donoghue GM. Profound deafness in childhood. The New England journal of medicine. 2010 Oct 7:363(15):1438-50. doi: 10.1056/NEJMra0911225. Epub     [PubMed PMID: 20925546]


Yoshinaga-Itano C, Sedey AL, Coulter DK, Mehl AL. Language of early- and later-identified children with hearing loss. Pediatrics. 1998 Nov:102(5):1161-71     [PubMed PMID: 9794949]


Deltenre P, Van Maldergem L. Hearing loss and deafness in the pediatric population: causes, diagnosis, and rehabilitation. Handbook of clinical neurology. 2013:113():1527-38. doi: 10.1016/B978-0-444-59565-2.00023-X. Epub     [PubMed PMID: 23622376]


Yoshimura H, Miyagawa M, Kumakawa K, Nishio SY, Usami S. Frequency of Usher syndrome type 1 in deaf children by massively parallel DNA sequencing. Journal of human genetics. 2016 May:61(5):419-22. doi: 10.1038/jhg.2015.168. Epub 2016 Jan 21     [PubMed PMID: 26791358]


Isgrig K, Shteamer JW, Belyantseva IA, Drummond MC, Fitzgerald TS, Vijayakumar S, Jones SM, Griffith AJ, Friedman TB, Cunningham LL, Chien WW. Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome. Molecular therapy : the journal of the American Society of Gene Therapy. 2022 Feb 2:30(2):975. doi: 10.1016/j.ymthe.2022.01.026. Epub 2022 Jan 20     [PubMed PMID: 35063081]