Hereditary Hearing Loss And Deafness Overview
Summary
This overview focuses on the clinical features and molecular genetics of common syndromic and nonsyndromic types of hereditary hearing loss.
The goals of this overview on hereditary hearing loss and deafness are the following:
Goal 1.
Describe the clinical characteristics of hereditary hearing loss and deafness.
Goal 2.
Review the causes of hereditary hearing loss and deafness.
Goal 3.
Provide an evaluation strategy to identify the genetic cause of hereditary hearing loss and deafness in a proband (when possible).
Goal 4.
Inform genetic counseling of family members of an individual with hereditary hearing loss and deafness.
Goal 5.
Review management of hereditary hearing loss and deafness.
Diagnosis
Clinical Characteristics
Differential Diagnosis
In children with delayed speech development, the auditory system should be assessed.
In the presence of normal audiometry associated with progressive loss of speech and temporal lobe seizures, the diagnosis of Landau-Kleffner syndrome should be considered.
Delayed speech suggesting possible hearing loss can also be seen in young children with autism spectrum disorder or specific speech and language disorders.
In developed countries approximately 80% of congenital hearing loss is due to genetic causes and the remainder to environmental (acquired) causes (Figure 2). Acquired causes should be differentiated from genetic causes to inform the evaluation and required ancillary testing (i.e., CT, MRI, and consultation with specialists) and to inform prognosis and treatment recommendations.
Figure 2.
Causes of prelingual hearing loss in developed countries
Acquired hearing loss in children commonly results from prenatal infections from "TORCH" organisms (i.e., toxoplasmosis, rubella, cytomegalovirus, and herpes), or postnatal infections, particularly bacterial meningitis caused by Neisseria meningitidis, Haemophilus influenzae, or Streptococcus pneumoniae. Meningitis from many other organisms including Escherichia coli, Listeria monocytogenes, Streptococcus agalactiae, and Enterobacter cloacae can also cause hearing loss.
In developed countries, however, the most common environmental, non-genetic cause of congenital hearing loss is congenital cytomegalovirus (cCMV) infection. Its overall birth prevalence is approximately 0.64%; 10% of this number have symptomatic CMV, which is characterized by a variable number and degree of findings including neurologic deficits (death, seizures, cerebral palsy), hepatic insufficiency, and characteristic rash. Hearing loss affects approximately 50% of symptomatic individuals with cCMV. The remaining 90% of individuals with cCMV are considered "asymptomatic"; of these up to 15% develop unilateral or bilateral hearing loss. Thus, the majority of individuals with hearing loss due to cCMV are classified as "asymptomatic."
The diagnosis of CMV hearing loss can be difficult to make, often can go unrecognized, and is characterized by variable-severity bilateral, asymmetric, or unilateral sensorineural hearing loss [Kenneson & Cannon 2007]. Testing for cCMV requires a high degree of suspicion and should be done within 21 days of birth given the ubiquity of the virus in the environment. Several states have introduced targeted testing for cCMV for newborns who fail their newborn hearing screen. Recognizing cCMV hearing loss is increasingly important given new studies that show improvement of hearing loss with antiviral therapy for persons with symptomatic CMV [Kimberlin et al 2015]. To date, however, the use of antivirals to treat hearing loss in persons with cCMV whose only manifestation is hearing loss is experimental.
Acquired hearing loss in adults, most often attributed to environmental factors, most likely reflects environmental-genetic interactions, the most frequent of which are age-related and noise-induced hearing loss. Although both of these types of hearing loss reflect complex "environmental-genetic" hearing loss, to date variants in only a few genes have been associated with these traits [Yamasoba et al 2013].
An environmental interaction pertinent to medical care is the observation that aminoglycoside-induced hearing loss is more likely in persons with specific variants in the mitochondrial genome (mtDNA) (see Nonsyndromic Hearing Loss and Deafness, Mitochondrial).
Management
Treatment of Manifestations
Ideally, the team evaluating and treating the deaf individual should consist of an otolaryngologist with expertise in the management of early childhood otologic disorders, an audiologist experienced in the assessment of hearing loss in children, a clinical geneticist, and a pediatrician. The expertise of an educator of the Deaf, a neurologist, and a pediatric ophthalmologist may also be required.
An important part of the evaluation is determining the appropriate habilitation option. Possibilities include hearing aids, vibrotactile devices, and cochlear implantation. Cochlear implantation can be considered in children older than age 12 months with severe-to-profound hearing loss.
The ultimate goal in the evaluation and treatment of a child with hereditary hearing loss and deafness is mainstream schooling. Research shows that diagnosis by age three months and habilitation by six months makes this goal possible for children with mild-to-moderate hearing loss. Cochlear implantation in children with severe-to-profound deafness who are part of mainstream education leads to social functioning and educational attainment that is indistinguishable from normal-hearing peers [Loy et al 2010, Langereis & Vermeulen 2015].
Recent research has focused on cochlear implant performance based on the gene involved. Due to the genetic heterogeneity of deafness, large sample sizes are difficult to obtain for performance on a per-gene basis. However, the data are clear that individuals with GJB2-related hearing loss (see Nonsyndromic Hearing Loss and Deafness, DFNB1) have excellent cochlear implant outcomes that are significantly better than those of individuals with environmental causes of deafness [Yoshida et al 2013, Abdurehim et al 2017].
In adults, cochlear implant performance may be compromised when the genetic defect affects the auditory nerve itself; however, this hypothesis requires further research [Shearer et al 2017].
DFNX3 is characterized by a mixed conductive-sensorineural hearing loss, the conductive component of which is caused by stapedial fixation. In contrast to other types of conductive hearing loss, surgical correction of DFNX3-related hearing loss can compromise hearing. An abnormal communication between the cerebrospinal fluid and perilymph can lead to fluid leakage ("perilymphatic gusher") at surgery and complete loss of hearing upon fenestration or removal of the stapes footplate.
Prevention of Primary Manifestations
Whenever a child presents with progressive sensorineural hearing loss and progressive ataxia, with or without neurologic or cutaneous symptoms, biotinidase deficiency should be considered, with initiation of treatment as early as possible to prevent irreversible sequelae.
Prevention of Secondary Complications
Regardless of its etiology, uncorrected hearing loss has consistent sequelae. Auditory deprivation through age two years is associated with poor reading performance, poor communication skills, and poor speech production. Educational intervention is insufficient to completely remediate these deficiencies. In contrast, early auditory intervention is effective – whether through amplification, otologic surgery, or cochlear implantation [Smith et al 2005].
Although decreased cognitive skills and performance in mathematics and reading are associated with deafness, examination of persons with hereditary hearing loss has shown that these deficiencies are not intrinsically linked to the cause of the deafness. For example, assessment of cognitive skills in individuals with GJB2-related hearing loss reveals a normal Hiskey IQ and normal reading performance after cochlear implantation [Bauer et al 2003]. Thus, early identification and timely intervention is essential for optimal cognitive development in children with prelingual deafness.
Surveillance
Sequential audiologic examinations are essential to:
- Document the stability or progression of the hearing loss;
- Identify and treat superimposed hearing losses, such as middle ear effusion.
In a person with autosomal recessive nonsyndromic hearing loss caused by pathogenic variants in SLC26A4, the hearing loss can progress and annual audiometric testing may be warranted. Additionally, thyroid function should be followed if the diagnosis is consistent with Pendred syndrome.
Agents/Circumstances to Avoid
Noise exposure is a well-recognized environmental cause of hearing loss. Since this risk can be minimized by avoidance, persons with documented hearing loss should be counseled appropriately.
Evaluation of Relatives at Risk
At a minimum, all children at risk for hereditary deafness and hearing loss should receive screening audiometry.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.