Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press The Epidemiology of Deafness Abraham M. Sheffield1 and Richard J.H. Smith2,3,4,5 1Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242 2Molecular Otolaryngology and Renal Research Laboratories (MORL), Department of Otolaryngology, University of Iowa, Iowa City, Iowa 52242 3Department of Molecular Physiology & Biophysics, University of Iowa, Iowa City, Iowa 52242 4Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242 5Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242 Correspondence: [email protected] Hearing loss is the most common sensory deficit worldwide. It affects ∼5% of the world population, impacts people of all ages, and exacts a significant personal and societal cost. This review presents epidemiological data on hearing loss. We discuss hereditary hearing loss, complex hearing loss with genetic and environmental factors, and hearing loss that is more clearly related to environment. We also discuss the disparity in hearing loss across the world, with more economically developed countries having overall lower rates of hearing loss compared with developing countries, and the opportunity to improve diagnosis, preven- tion, and treatment of this disorder. earing loss is the most common sensory refer to people with mild-to-moderate (and Hdeficit worldwide, affecting more than half sometimes severe) hearing loss, whereas the a billion people (Smith et al. 2005; Wilson et al. term “deaf” (lower case “d”) is more commonly 2017). Normal hearing is defined as having hear- reserved for those with severe or profound hear- ing thresholds of ≤25 dB in both ears. The World ing loss (Smith et al. 2005; also seewho.int/news- Health Organization (WHO) defines hearing room/fact-sheets/detail/deafness-and-hearing- loss as a speech-frequency pure tone average loss). The term “Deafness” (upper case “D”) >25 dB at 0.5, 1, 2, and 4 kHz in the better hear- describes a cultural group united by the use of ing ear (Yamasoba et al. 2013). Disabling hearing sign language for communication. People with loss is defined as hearing loss >40 dB in the better any degree of hearing loss are sometimes de- www.perspectivesinmedicine.org hearing ear in adults and >30 dB in the better scribed as “hearing impaired.” Although this hearing ear in children (see who.int/news- term is intended to be neutral, it may arouse room/fact-sheets/detail/deafness-and-hearing- negative feelings in some, especially among loss). Degrees of hearing loss are classified those in the Deaf community who do not view as mild (26 dB to 40 dB), moderate (41 dB to hearing loss as an impairment (Smith et al. 55 dB), moderately severe (56 dB to 70 dB), se- 2005). vere (71 dB to 90 dB), or profound (≥91 dB) Because of the great heterogeneity that exists, (Koffler et al. 2015). there are many ways to describe and categorize Although there is no clear demarcation, the hearing loss. These include etiology, age of onset, term “hard of hearing” is sometimes used to time of onset in relation to language develop- Editors: Guy P. Richardson and Christine Petit Additional Perspectives on Function and Dysfunction of the Cochlea available at www.perspectivesinmedicine.org Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a033258 1 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press A.M. Sheffield and R.J.H. Smith ment, clinical presentation, severity, frequency loss is subdivided into syndromic or nonsyn- loss, number of ears affected, and anatomic de- dromic, based on the presence or absence of fect. In terms of anatomic defects, there are two coinherited anomalies. Syndromic and nonsyn- broad categories: conductive hearing loss (CHL) dromic conditions are further subdivided by in- and sensorineural hearing loss (SNHL). Mixed heritance pattern: autosomal dominant, auto- hearing loss is athird type that is used to describe somal recessive, X-linked, and mitochondrial cases in which both CHL and SNHL are present (Shibata et al. 2015). Complex inheritance, in in the same ear. Etiologically based classification which there are significant contributions from of hearing loss can be broadly divided into ge- both genetic and environmental factors, will netic versus nongenetic. It is important to note also be discussed. Wewill concludewith address- that genetic hearing loss is not synonymous with ing environmental factors. congenital hearing loss. Congenital hearing loss There is significant disparity in rates of hear- simply refers to hearing loss that is present since ing loss between developed nations and devel- birth regardless of etiology. Genetic hearing loss oping nations (see Fig. 1). It should be noted that refers to a genetically inherited etiology, which data on the incidence and causes of hearing loss may be present at birth (i.e., congenital) or de- are most readily available from developed na- velop at any time thereafter (Shibata et al. 2015). tions in which there are newborn hearing screen- This review will discuss the epidemiology of ing programs. The information is not as well hearing loss. We will address genetic, as well as documented for most developing countries. environmental causes of hearing loss. Hearing We attempt to include appropriate international loss of genetic etiology can be subcategorized data where possible, but many of the epidemio- into simple Mendelian inheritance versus com- logical studies come out of the United States and plex inheritance. Mendelian inherited hearing Europe. Prevalence of disabling hearing loss by region 10% 9% 8% 7% 6% www.perspectivesinmedicine.org 5% 4% 3% Prevalence of hearing loss Prevalence 2% 1% 0% High-income Central/Eastern Sub-Saharan Middle East and South AsiaAsia Pacific Latin America and East Asia nations Europe and Central Africa North Africa Caribbean Asia Prevalence of disabling hearing loss (>30 dB) in children (<15 years old) Prevalence of disabling hearing loss (>40 dB) in adults (15+ years old) Figure 1. Prevalence of disabling hearing loss in adults (15 years and older) and children (younger than 15 years). Disabling hearing loss is defined by the World Health Organization (WHO) as thresholds >30 dB for children and >40 dB for adults. (Data based on 2018 WHO Global Estimates on Prevalence of Hearing Loss.) 2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a033258 Downloaded from http://perspectivesinmedicine.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press The Epidemiology of Deafness NONSYNDROMIC GENETIC HEARING LOSS been identified as causally related to ARNSHL OVERVIEW (see hereditaryhearingloss.org). The first causa- Approximately half of hearing loss cases have a tive locus was mapped in 1994 (Guilford et al. genetic etiology (see Fig. 2). Genetic hearing loss 1994). Three years later, the gene at this locus fi accountsforatleast50%–60%ofchildhoodhear- was identi ed as GJB2 (Kelsell et al. 1997). GJB2 ing loss cases in developed countries (Koffler encodes connexin 26, a protein that oligomer- et al. 2015). A simple Mendelian inheritance pat- izes to form a connexon. Connexons in adjacent tern is common for genetic hearing loss. Non- cells dock to form a gap junction, which are syndromic describes hearing loss of genetic eti- critical in the inner ear for recycling potassium ology with no other phenotypic manifestations. and other ions to maintain cochlear homeosta- Nonsyndromic SNHL accounts for ∼70% of sis (Mammano 2018). Mutations in GJB2 are congenital genetic hearing loss. The most com- the most common cause of severe-to-profound mon inheritance pattern of congenital nonsyn- ARNSHL, accounting for up to 50% of people dromic SNHL is autosomal recessive (∼75%– with this degree of congenital hearing loss in 80%). Autosomal dominant SNHL represents many world populations. There is great allelic ∼20%, X-linked <2%, and mitochondrial <1% heterogeneity, with >100 different deafness- fi (Shibata et al. 2015). Nonsyndromic genetic causing mutations identi ed in this single gene. loci for hearing loss are named with the conven- Notably, different mutations in GJB2 predomi- tion of DFNB# (autosomal recessive), DFNA# nate in different populations. For example, the (autosomal dominant), and DFNX# (X-linked). 35delG mutation is most common in Europeans To date, there are 157 genetic loci with 110 iden- and European-Americans and has a carrier fre- ∼ tified genes (see hereditaryhearingloss.org). quency of 2.5% in the Midwestern United States. In comparison, the 167delT mutation has a carrier frequency of ∼4% in the Ashkenazi Autosomal Recessive Nonsyndromic Jewish population and the 235delC mutation is Hearing Loss the most common GJB2 mutation in the Japa- Autosomal recessive nonsyndromic hearing loss nese (Shibata et al. 2015). (ARNSHL) is the most common type of genetic In a recent study using comprehensive ge- hearing loss. It is most often characterized by netic testing by means of targeted genomic en- prelingual onset (before speech development) richment and massively parallel sequencing and is usually severe-to-profound across all fre- (TGE+MPS) to identify the genetic etiology of quencies. According to the Hereditary Hearing hearing loss in