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].

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.

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.

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References

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