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Congenital Deafness

Congenital deafness (CD) is a condition of impaired hearing due to genetic or pregnancy-related causes in infants with a highly variable onset of initial symptoms. Genetic CD is most probably related with pathological gene mutations while acquired CD normally correlates with irregularities during pregnancy. Thorough screening for temporal bone malformations and a detailed family background check in combination with molecular genetic tests yield a reliable diagnosis. A multidisciplinary team of medical professionals and educators is necessary to support infant patients and their parents.


Presentation

Most generally speaking, failure to reach language learning and noise response milestones in infants may indicate a possible case of congenital deafness (CD) and motivate further examinations [1].

CD appears as an isolated symptom in eighty percent of all reported cases of genetic CD. So far, genetic CD has been shown to be passed on in either an autosomal dominant, autosomal recessive or in an X-linked manner. Three out of four CD cases can be rationalized with an autosomal recessive inheritance mechanism. An example of an autosomal dominant presentation of nonsyndromic genetic CD involves a mutation in type XI collagen [1] [2].

In twenty percent of diagnosed genetic CD cases, CD presents together with a plethora of other symptoms in the context of highly complex disorders. Most frequent syndromes related with genetic CD are the Alport Syndrome, the Brancio-Oto-Renal Syndrome, the X-linked dominant Charcot Marie Tooth disease, X-linked hereditary axonal neuropathies, autosomal recessive demyelinating neuropathy, autosomal dominant hereditary neuropathies type I and II [3], Goldenhar Syndrome [4], Jervell and Lange-Nielsen Syndrome, X-linked recessive Mohr-Tranebjaerg Syndrome, Norrie Disease, Pendred Syndrome, Stickler Syndrome, Treacher Collins Syndrome, Waardenburg Syndrome, Usher Syndrome and in some cases mitochondria-related syndromes [5] [6] [7].

In twenty percent of overall cases, CD presents as an acquired disorder. Cochlear malformations are usually the main culprits for this manifestation of CD. A premature halt in cochleal development in embryos is often the starting point for Mondini dysplasia [8]. In a related anomaly, the CHARGE association (short-hand for "Coloboma, Heart disease, choanal Atresia, Retarded development, Genital hypoplasia, Ear anomalies") features hypoplasia of the external ear and progressive deafness. CHARGE patients suffer from a Mondini type deformity and an absence of semicircular canals [9]. Enlarged Vestibular Aqueduct Syndrome may also present with a fluctuating sensorineural loss of hearing [10].

Delayed Speech Development
  • Differential Diagnosis of Hereditary Hearing Loss and Deafness In children with delayed speech development, the auditory system should be assessed.[ncbi.nlm.nih.gov]
  • If an individual or the parents of a child raise concern about the possibility of hearing loss or, if the child is young, and there is concern regarding delayed speech development or poor social interaction, the initial evaluation should include a detailed[nature.com]
Family History of Deafness
  • history of deafness or those born with low birth weight, birth asphyxia, jaundice or meningitis, for early assessment of hearing, to ensure prompt diagnosis and appropriate management, as required; Identification and management Early detection and intervention[who.int]
  • Risk factors Family history of deafness. Infection: congenital (eg, rubella), mumps, meningitis. Ototoxic medications: in utero or postnatal. Low birth weight, prematurity, low birth Apgar scores, prolonged mechanical ventilation.[patient.info]
  • The subsequent offspring of a hearing couple with one deaf child and an otherwise negative family history of deafness have an 18% empiric probability of deafness in future children [ Green et al 1999 ].[ncbi.nlm.nih.gov]
Fishing
  • Mapping of the deletion was performed using fluorescence in situ hybridization (FISH) analysis with region-specific yeast artificial chromosome (YAC) clones.[ncbi.nlm.nih.gov]
Microdontia
  • We present an 8-year-old boy with folate receptor alpha (FRα) defect and congenital deafness with labyrinthine aplasia, microtia and microdontia (LAMM syndrome).[ncbi.nlm.nih.gov]
  • Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706[ncbi.nlm.nih.gov]
Hearing Impairment
  • Two boys who both had a profound bilateral hearing impairment met at a specialized sign preschool.[ncbi.nlm.nih.gov]
  • Newborns (born during 2016 and 2017) from across Victoria diagnosed with permanent hearing impairment in both ears of moderate or greater severity are being offered genomic sequencing in addition to their usual care.[melbournegenomics.org.au]
  • Three of 39 hearing impaired subjects were excluded; one due to insufficient information on the probable cause of the hearing impairment and the other two due to a non-genetic origin of the hearing deficit.[nature.com]
  • In type I, there is both hearing impairment and vestibular impairment. In type II, there is hearing impairment without vestibular impairment. In type III, there is variable amounts of vestibular impairment.[american-hearing.org]
Hearing Problem
  • While these signs don't necessarily mean that your child has a hearing problem, they could be indicators of one.[pamf.org]
  • Problems Fungal Ear Infections Outer Ear Infections Middle Ear Infections Tinnitus Can You Prevent Tinnitus Links Between Hearing Loss And Tinnitus Tinnitus Causes Tinnitus Explained Tips For Dealing With Tinnitus About About Us What Makes Us Different[hiddenhearing.co.uk]
  • Screening tests for the GJB2 gene are available for at risk individuals to help them determine their risk of having a child with hearing problems. Patient Health Home Copyright 2018 American Academy of Otolaryngology–Head and Neck Surgery.[entnet.org]
  • Some of the many genetic disorders that can cause hearing loss include osteogenesis imperfecta, Trisomy 13 (Patau syndrome) and Treacher Collins syndrome prenatal exposure to disease – a baby will be born deaf or with hearing problems if they are exposed[betterhealth.vic.gov.au]
Vocal Tic
  • His tic disorder rapidly accelerated from the age of seven over a six-month period and soon sign language was incorporated into tics as complex "vocal" tics.[ncbi.nlm.nih.gov]

Workup

An audiometric test is the logical starting point to build a diagnosis. Patients with slowly progressing hearing loss should be checked for Alport Syndrome, Stickler Syndrome and Pendred Syndrome with a particular focus on a computed tomography (CT) investigation of the temporal bone. In infants, which are nonresponsive to noise, an auditory brainstem response (ABR) test should be considered. If hearing loss occurs as an isolated symptom, CD may be genetically caused. In this case, a thorough analysis of the patient's family history is highly recommended. In order to identify the specific mutation causing genetic CD, molecular genetic tests can screen for pathological mutations [11] [12].

If the cause of a diagnosed hearing loss remains unidentified, a clinical examination of the ear anatomy and other features linked to syndromic deafness is necessary. Checks should mainly focus on branchial cleft pits, cysts, preauricular pits, telecanthus, white forelock, pigmentary anomalies, goiter, craniofacial anomalies, heterochromia iridis and pigmentary retinopathy [13].

Fast or slowly progressing hearing loss can be caused by temporal bone anomalies, neoplasms, immunology-related deafness, trauma, infections (syphilis, Lyme disease) and other disturbances. A temporal bone CT scan will be able to detect malformations of the inner ear like Mondini deformities, Michel aplasia, a dilated vestibular aqueduct and a dilation of the internal auditory canal. If a CT scan of the temporal bones reveals an enlarged/dilated vestibular aqueduct or Mondini dysplasia, screening for pathogenic variants of SLC26A4 is advisable [13].

In families accumulating autosomal dominant CD, it may be useful to devise computer algorithms to screen for candidate mutations by selective audioprofiling [14]. High-throughput multi-gene assays may also provide a useful and time-efficient means for a reliable diagnosis [15].

A histological examination of the temporal bone may also be taken into consideration as a last resort.

Nephrolithiasis
  • Her past medical history was significant for an open operation for left nephrolithiasis five months before admission. She had no history of congenital heart defect, intravenous drug use or central venous line insertion.[ncbi.nlm.nih.gov]

Treatment

Treatment of CD typically involves an expert team of specialized otolaryngologists, audiologists, clinical geneticists and pediatricians. It is also recommended to consult neurologists, pediatric ophthalmologists and sign language educators in selected cases. CD patients should be provided with hearing aids, if necessary. In severe cases of hearing loss in the pre-lingual stage, cochlear implants are highly advisable for children older than twelve months [16] [17].

In case of a diagnosed Pendred Syndrome with abnormal thyroid function, a thyroid hormone replacement therapy should be prescribed [13]. Young CD patients with moderate hearing loss and their families should take lip-reading and sign language classes as soon as possible to maintain active communication. Students suffering from CD will likely require special attention of their teachers [13].

Semiannual audiometric checks and consultations with an otolaryngologist are reasonable to track the stability and/or progression of CD.

Prognosis

A proper treatment of CD starting as early as possible is the best guarantee for a life without social restrictions.

Untreated CD in children may lead to difficulties in sound localization and in discerning sounds from background noise. In severe cases, children will suffer a life-long limitation of their language, reading and math skills. These children face an increased risk of school failure, language barriers, fewer opportunities for success and financial wealth and, therefore, a significantly reduced quality of life [13].

Etiology

While CD can be caused by a variety of genetic mutations, there are also nongenetic factors that involve pre-, peri- and postnatal irregularities, which account for up to twenty percent of diagnosed CD cases. So far, the following pregnancy-related causes have been identified: maternal infections with rubella, cytomegalovirus, syphilis, HIV or herpes simplex, infant prematurity, low birth weight, birth injuries, severe hyperbilirubinaemia and sepsis, maternal drug (cocaine, streptomycine) and/or alcohol consumption during pregnancy, Rhesus factor complications during birth, jaundice, maternal diabetes as well as toxemia and anoxia in utero [18].

Genetic CD has been traced back to a large but still incomplete set of protein mutations. In the majority of cases, mutations of the gap junction proteins connexin-26 and connexin-30 encoded in the gene GJB2 and GJB6, respectively, are responsible for the manifestation of genetic CD [18]. A comprehensive review of currently known CD-related mutations can be retrieved from the Hereditary Hearing Loss platform [19].

Epidemiology

CD has a prevalence of 1 in 2 000 infants. Genetic CD with autosomal recessive inheritance is the most frequent manifestation. Non-inherited abnormalities of the inner ear account for roughly 20% of all CD cases. Genetic CD affects different ethnicities with different mutations. For instance, connexin-related hearing loss in Hispanic infants has been reported to be less frequent than in other ethnic groups [20]. Male infants have a larger probability to suffer from the autosomal dominant manifestation of genetic CD [21].

Sex distribution
Age distribution

Pathophysiology

In genetic CD, mutations of the connexin protein family have a detrimental effect on the temporal bone and on structural elements of the inner ear leading to a large set of abnormalities. Partial or complete loss of hair cells, and impaired functions of supporting cells, spiral ligaments, stria vascularis, the basilar membrane, spiral ganglion cells and of the auditory nerve have been reported in histological studies [19] [22]. In many cases, CD is caused by an impaired or completely absent mechanical excitability of audiosensitive hair cells [23].

CD can also progress with age or as a consequence of environmental influences such as excessive noise exposure.

Prevention

A healthy maternal lifestyle during pregnancy is a major factor to prevent acquired CD. Prenatal audiometric tests may be an option. In genetic CD, parents should be aware of their family disease history and should immediately seek medical advice, if the infant does not respond to sounds and noises appropriately. Ignoring the early onset of symptoms will likely have disadvantageous long-term consequences for the child.

In case of diagnosed CD with professional support providing adequate hearing aids, patients are strongly advised to avoid noisy environments and loud music at any time in order to preserve hearing function.

Summary

Congenital deafness is either genetically caused or acquired in utero through maternal lifestyle and/or infection. The earliest symptom in infants is an impaired sound response and can start at any time in the pre-lingual phase. In the majority of cases, Congenital Deafness is caused by a genetic mutation of the connexin protein family. Diagnosis should start with an audiometric test. A detailed analysis of the family history and CT scans of the temporal bone as well as molecular genetic tests are strongly recommended. A multidisciplinary team of experts will be necessary to consult on adequate treatments (e.g. cochlear implants) and training (e.g. sign language classes) for the child and its whole family.

Patient Information

Congenital deafness can occur in infants and children at any age and is characterized by a reduced noise response that can lead to increased social isolation and lack of success at school. Parents are strongly advised to be aware of their family history of deafness and immediately consult a medical professional, if their child does not appropriately respond to noise. You may need to learn sign language in order to be able to communicate with your child, if the disorder is progressing fast. Avoiding loud noises is imperative to stabilize hearing functions, but not a guarantee.

References

Article

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  2. De Leenheer EM, Kunst HH, McGuirt WT, et al. Autosomal dominant inherited hearing impairment caused by a missense mutation in COLA11A2 (DFNA13). Arch Otolaryngol Head Neck Surg. 2001; 127(1):13-17.
  3. Stojkovic T, Latour P, Vandenberghe A, Hurtevent JF, Vermersch P. Sensorineural defaness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q). Neurology. 1999; 52:1010-1014.
  4. Scholtz AW, Fish JH III, Kammen-Jolly K, et al. Goldendar’s syndrome: congential hearing deficit of conductive or sensorineural origin?. Otology Neurotol. 2001; 22:501-505.
  5. Sue CM, Lipsett LJ, Crimmins DS, et al. Cochlear origin of hearing loss in MELAS syndrome. Ann Neurol. 1998; 43:350-359.
  6. Yamasoba T, Tsukuda K, Oka Y, Kobayashi T, Kaga, K. Cochlear histopathology associated with mitochondrial transfer RNA (leu-UUR) gene mutation. Neurology. 1999; 52:1705-1707.
  7. El-Schahawi M, Lopez de Munain A, Sarrazin AM, et al. Two large Spanish pedigrees with nonsyndromic sensorineural deafness and the mtDNA mutation at nt 1555 in the 12S rRNA gene. Evidence of heteroplasmy. Neurology. 1997; 48:453-456.
  8. Strome SE, Baker KB, Langman AW. Imaging case of the month: Inner ear malformation. Am J Otol. 1998; 19:396-397.
  9. Wiener-Vacher SR, Denise P, Narcey P, Manach Y. Vestibular function in children with the CHARGE association. Arch Otolaryngol Head Neck Surg. 1999; 125(3):342-347.
  10. Murray LN, Tanaka GJ, Cameron DS, Gianoli GJ. Coronal computed tomography of the normal vestibular aqueduct in children and young adults. Arch Otolaryngol Head Neck Surg. 2000; 126(11):1351-1357.
  11. Usami S, Nishio SY, Nagano M, Abe S, Yamaguchi T, Deafness Gene Consortium. Simultaneous Screening of Multiple Mutations by Invader Assay Improves Molecular Diagnosis of Hereditary Hearing Loss: A Multicenter Study. PLOS ONE. 2012; 7(2):e31276.
  12. Vore AP, Chang EH, Hoppe JE, et al. Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness. Arch Otolaryngol Head Neck Surg. 2005; 131(12):1057–1063.
  13. Alasti F, Van Camp G, Smith RJH. Pendred Syndrome/DFNB4. In: Pagon RA, Adam MP, Ardinger HH, et al eds. GeneReviews(R). Seattle, WA: University of Washington. 1993-2017. Chapter 158. Available online: https://www.ncbi.nlm.nih.gov/books/NBK1467/. Accessed April 25, 2017.
  14. Hildebrand MS, Tack D, McMordie SJ, et al. Audioprofile-directed screening identifies novel mutations in KCNQ4 causing hearing loss at the DFNA2 locus. Genet Med. 2008; 10(11):797–804.
  15. Shearer AE, DeLuca AP, Hildebrand MS, et al. Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci U S A. 2010; 107(49):21104–21109.
  16. Bauer PW, Geers AE, Brenner C, Moog JS, Smith RJ. The effect of GJB2 allele variants on performance after cochlear implantation. Laryngoscope. 2003; 113(12):2135–2140.
  17. Smith RJ, Bale JF Jr, White KR. Sensorineural hearing loss in children. Lancet. 2005; 365(9462):879–890.
  18. Eisen MD, Ryugo DK. Hearing molecules: contributions from genetic deafness. Cell Mol Life Sci. 2007; 64(5):566-580.
  19. Van Camp G, Smith R. Cloned genes for nonsyndromic hearing loss. Hereditary Hearing Loss Homepage. Available at http://hereditaryhearingloss.org/main.aspx?c=.HHH&n=86163. Accessed April 25, 2017.
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  23. Brini M, Di Leva F, Domi T, Fedrizzi L, Lim D, Carafoli E. Plasma-membrane calcium pumps and hereditary deafness. Biochem Soc Trans. 2007; 35(5):913-918.

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