Genetic Sensorineural Hearing Loss

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Of the more than 4000 infants born deaf each year, more than half have a hereditary disorder. Hereditary disorders must be differentiated from acquired hearing losses. Not all hereditary hearing loss is present at birth; some children inherit the tendency to develop hearing loss later in life.

Genetic sensorineural hearing loss (SNHL) includes a broad range of disorders that affect infants, children, and adults. Affected individuals may have unilateral or bilateral hearing loss ranging from mild to profound. This article, like most related discussions, focuses on childhood hearing loss, with consideration of a few forms of adult-onset hearing loss.

Volumes of texts and journals are dedicated to the pathophysiology of genetic hearing loss and can not be easily summarized in a few paragraphs. Interestingly, note that as our understanding of the molecular basis of genetic hearing loss increases, so does our understanding of the molecular basis of hearing itself, although it remains still largely unsolved. ^{[1, 2]}

First, we must understand that genetic hearing loss seems to breach all categories of hearing loss, including the following: congenital, progressive, and adult onset; conductive, sensory, and neural; syndromic and nonsyndromic; high-frequency, low-frequency, or mixed frequency; and mild or profound. Genetic hearing loss may show patterns of recessive, dominant, or sex-linked inheritance and may be a result in mutation of both cellular or mitochondrial DNA (and RNA, in the case of mitochondrial genes). Genetic hearing loss may be subject to environment and aging, such as noise-induced or age-induced hearing loss.

New genetic mutations are linked to hearing loss every year. More than 100 loci have been identified involving genes that code for proteins involved in the structure and function of hair cells, supporting cells, spiral ligament, stria vascularis, basilar membrane, spiral ganglion cells, auditory nerve, and virtually every structural element of the inner ear. ^[3]

See the image below.

Dysfunctional proteins have been identified in the impaired molecular-physiologic processes of potassium and calcium homeostasis, ^[4] apoptotic signaling, ^[5] stereocilia linkage, ^[6] mechanicoelectric transduction, electromotility, and other processes. ^[1] Eisen and Ryugo provide an excellent review of the molecular pathophysiology of genetic hearing loss. ^[1]

United States

According to the National Institute on Deafness and Other Communication Disorders (NIDCD), hearing loss affects approximately 28 million Americans and approximately 17 in 1000 children and adolescents younger than 18 years. The average incidence of hearing loss in neonates in the United States is 1.1 per 1000 with variability among states ranging between 0.22 and 3.61 according to Mehra et al. ^[7] In the study by Mehra et al, the prevalence of childhood and adolescent hearing loss was 3.1%, with higher rates in Hispanic Americans and in families with lower incomes. ^[7]

Congenital hereditary hearing loss must be differentiated from acquired hearing loss. More than half of all cases of prelingual deafness are genetic. The remaining 40-50% of all cases of congenital hearing loss are due to nongenetic effects, such as prematurity, postnatal infections, ototoxic drugs, or maternal infection (with cytomegalovirus [CMV] or rubella). Most cases of genetic hearing loss are autosomal recessive and nonsyndromic. Hearing loss that results from abnormalities in connexin 26 and connexin 30 proteins likely account for 50% of cases of autosomal recessive nonsyndromic deafness in American children.

The incidence of hearing loss increases with age. Loss affects 314 in 1000 people older than 65 years and 40-50% of people aged 75 years or older. Adult-onset hearing loss can be attributed to normal aging processes and environmental triggers. However, an individual’s genetic predisposition should not be underestimated, as illustrated by aminoglycoside-induced ototoxicity and the predisposition to noise-induced hearing loss.

Current statistics can be found on the Early Hearing Detection & Intervention (EHDI) Program Web site published by the Centers for Disease Control and Prevention.

International

Genetic sensorineural hearing loss (SNHL) appears to occur twice as often in developed countries as in underdeveloped countries. Hearing impairment affects up to 30% of the international community, and estimates indicate that 70 million persons are deaf. In addition to ancestry and race, the proportions of hereditary versus acquired and syndromic versus nonsyndromic hearing losses across populations is highly variable and is heavily influenced by multiple factors, some likely not yet identified, including drift of populations, frequency of consanguinity, and health status.

Estimating the prevalence of hereditary hearing loss in populations across the world is very difficult because access to health care, poor health conditions, and a low level of awareness of hearing loss is compounded by a higher frequency of complicating risk factors such as neonatal distress, prematurity, high fever, otitis media, meningitis, ototoxic medications, and illnesses such as rubella. ^[8]

An estimated 30,000 infants are born with sensorineural hearing loss each year in China, which has a population of about 1.3 billion, but the percentage of these hearing losses attributable to heredity is not known. ^[9] Saunders et al demonstrated a prevalence of significant hearing loss of 18% in a group of school-aged children in rural Nicaragua with a familial history of hearing loss in 24% of the children with hearing loss .  ^[8] Large-scale epidemiologic studies are needed and will become more feasible as molecular testing is made available to the world’s populations.

The 350,000 individuals who are profoundly deaf in the United States earn approximately 30% less than the general population. Among school-aged children with hearing loss, approximately 52,000 attend schools or programs for the deaf, 100,000 are enrolled in special deaf-education classes, and 250,000 participate in standard public school settings. The overall cost for deafness education is estimated to be $121 billion.

Genetic hearing loss does have significant ethnic links. Angeli recently reviewed the ethnic variability of DGNB1 and showed greater allelic variability in Hispanics. ^[10] Schimmenti et al showed a lower prevalence of connexin-related hearing loss in Hispanic infants. ^[11]

Before universal hearing screening for newborns, less than 50% of children who had hearing impairment were identified before the age of 3 years. Detection of risk factors (eg, prematurity, low birth weight, low Apgar scores) helps in identify less than 50% of infants who have or who are at risk for hearing loss. In one study, 78% of infants identified with hearing loss were in the well-baby nursery and not the neonatal intensive care nursery. ^[12] This finding emphasized the ineffectiveness of screening on the basis of risk identification alone. Thirty-six states now mandate universal screening of newborns resulting in earlier identification and treatment. Hereditary hearing loss may also be progressive or adult in onset.

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Stephanie A Moody Antonio, MD Associate Professor, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School

Stephanie A Moody Antonio, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, Virginia Society of Otolaryngology-Head and Neck Surgery, American Neurotology Society, American Medical Association

Disclosure: Nothing to disclose.

Barry Strasnick, MD, FACS Chairman, Professor, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School

Barry Strasnick, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Auditory Society, American College of Surgeons, American Medical Association, American Tinnitus Association, Ear Foundation Alumni Society, Norfolk Academy of Medicine, North American Skull Base Society, Society of University Otolaryngologists-Head and Neck Surgeons, Vestibular Disorders Association, Virginia Society of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ted L Tewfik, MD Professor of Otolaryngology-Head and Neck Surgery, Professor of Pediatric Surgery, McGill University Faculty of Medicine; Senior Staff, Montreal Children’s Hospital, Montreal General Hospital, and Royal Victoria Hospital

Ted L Tewfik, MD is a member of the following medical societies: American Society of Pediatric Otolaryngology, Canadian Society of Otolaryngology-Head & Neck Surgery

Disclosure: Nothing to disclose.

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;Preacute Population Health Management;The Physicians Edge<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; for: Rxblockchain;Bridge Health.

Robert A Battista, MD, FACS Assistant Professor of Otolaryngology, Northwestern University, The Feinberg School of Medicine; Physician, Ear Institute of Chicago, LLC

Robert A Battista, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, Illinois State Medical Society, American Neurotology Society, American College of Surgeons

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Karen K Hoffmann, MD, to the development and writing of this article.

Genetic Sensorineural Hearing Loss

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