epidemiological studies on hearing impairment with ...

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EPIDEMIOLOGICAL STUDIES ON HEARING IMPAIRMENT WITH REFERENCE TO GENETIC FACTORS IN SICHUAN, CHINA XUE ZHONG

Lru,

MD, PHD

RICHMOND, VIRGINIA

E.

LI RONG XU, MD

YINGHU, PHD

CHENGDU, CHINA

WASHINGTON, DC

ARISTIDES SISMANIS, MD

SI LING ZHANG, MD

YINGXU, MD

RICHMOND, VIRGINIA

CHENGDU, CHINA

CHENGDU, CHINA

WALTER

NANCE, MD, PHD

RICHMOND, VIRGINIA

Hearing impairment is the most common disorder of sensorineural function and is an economically and socially important cause of human morbidity. A large-scale epidemiological survey of hearing loss was conducted with 126,876 un selected subjects (63,741 male and 63,135 female) from Sichuan, China. The overall prevalence of hearing loss was 3.28% (4,164 of 126,876), and the prevalence increased with age, reaching 12.8% (1,465 of 11,421) at 60 years of age. In 73.03% of all cases (3,041 of 4,164), the hearing loss was sensorineural, and in 20.39% (849 of 4, 164), it was conductive; the remaining cases (6%) were mixed hearing loss. Bilateral loss was found in 74.5% of cases (3, I 03 of 4, 164). In 63.79% of cases (2,656 of 4, 164), the degree of hearing loss was less than 55 dB hearing level (HL), and in 5.67% of cases (236 of 4, 164), it was greater than 90 dB HL. The prevalence of hearing loss in childhood «15 years of age) was 0.67% (227 of 34,157), of which 57.7% of cases were conductive and 38.8% were sensorineural. The prevalence of genetic hearing loss was 0.28% (349 of 126,876). Persons who lived in the flatlands appeared to have a higher prevalence than those who lived in the hills. Several ethnic groups, including Tibetans, the Yi, and the Lisu, had a higher prevalence of hearing loss. Presbycusis, otitis media, and genetic factors were the most commonly recognized causes of hearing impairment overall, but otitis media and genetic factors were the main causes of hearing loss in children. Causes for the observed differences in prevalence and etiologic factors between China and industrialized countries will be discussed. In China, infections and genetic factors appear to be of major importance as causes of hearing loss. KEY WORDS -

Chinese, epidemiology, etiology, genetic deafness, hearing loss.

demiologists, statisticians, and computer workers collaborated on the field, clinical, or laboratory work. As part of this project, subjects with hearing impairment were surveyed, and the prevalence and causes of hearing loss in the general population were estimated.

Hearing loss is a major community health problem and a serious medico social problem. There have been many investigations on population prevalence and causes of hearing loss in industrialized countries.l> but few such studies have been conducted in developing nations, including China. However, such knowledge about the frequency and causes of hearing loss is an essential prerequisite to the rational planning of research and the provision of health care.

METHODS

Selection ofPopulation and Sampling. Sichuan is a large province in southwestern China. Ninety-seven percent of its population is Chinese (Han). The rest are Yi, Tibetan, Qiang, Lisu, and others. The referral sites were selected on the basis of a stratified random sampling method considering the density and geographic and urban-rural distribution of the population, so that the results would be as representative of the whole province as possible. The area of Sichuan is 570,000 km-, about 6% of the total area of China.

Sichuan is the most populous province in China, with 104 million people (1987). It is quite representative of all China in its economic, cultural, and demographic aspects. During 1986 and 1987, a largescale epidemiological survey of more than 100 genetic diseases was carried out.f The survey covered 100 million people, a sampling frame population of 11,168,000, and a study group of 126,876 people. More than 400 doctors, paramedical personnel, epi-

From the Departments of Human Genetics (Liu, Nance) and Otolaryngology (Liu, Sisrnanis), Medical College of Virginia, Richmond, Virginia, the Laboratory of Population Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, DC (Hu), and the Department of Otolaryngology, West China University of Medical Sciences (Liu, L. R. Xu), and the Department of Epidemiological Survey, Sichuan Family Planning Research Institute (Zhang, Y. Xu), Chengdu, China. This work is part of the project Genetico-Epidemiological Surveys of the General Population in Sichuan. The data analysis of this work was partly supported by the National Institute on Deafness and Other Communication Disorders (NIDCD R03 DC04530), the Deafness Research Foundation, the National Institutes of Health (NIH DC02530), and the Foundation Fighting Blindness. CORRESPONDENCE - Xue Zhong Liu, MD, PhD, Dept of Human Genetics, Medical College of Virginia, Sanger Hall, 1101 E Marshall SI. PO Box 980033, Richmond, VA 23298-0033.

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Liu et al, Epidemiology of Hearing Loss

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TABLE I, PROTOCOL OF HEARING SCREENING USED IN THIS SURVEY Stage

First

Second

Third

Methods Used

Aims

Questionnaires Whispered voice Behavioral test History-taking otolaryngological examinations Otoscopy Tuning fork tests Pure tone audiometry Otoimmittance if available Examination by other specialists Nonaudiological tests if necessary Establish pedigrees of unknown cases Repeat examinations used at second stage for available family members Population genetic analysis

Geographically, Sichuan consists of the West Sichuan Plateau, with an average altitude of more than 3,000 m, and the Sichuan Basin, below which lies Chengdu Plain. The land slopes gradually downward from northwest to southeast. Three land types - mountainous, hilly, and flat - can be distinguished. Its population distribution is uneven, with the urban-rural ratio about I :4. Each referral site consisted of 2 to 4 neighboring villages or residents' committees (in towns) with about 3,000 people or 500 to 600 families. Selected population groups, such as army units, schools, colleges, and sites with massive emigration in the past 20 to 30 years, were excluded. Forty-two villages or towns were chosen to be referral sites and were compatible with the above requirements.

Screening Procedure. A 3-stage protocol was adopted in.the current survey (Table I). In the first stage, all inhabitants of a referral site were questioned and examined by means of a standardized comprehensive questionnaire and examination scheme by one of the team of doctors and secondary medical personnel. 6 The questionnaire used in this stage included medical and family history of all conditions investiTABLE 2. QUESTIONNAIRE FOR SCREENING OF HEARING LOSS AT FIRST STAGE For adults: Do you have any hearing impairment? How old were you when you noticed your hearing problem? Is there a history of hearing loss in your family? For parents with children: Do you think your child has normal hearing? Does your child seem startled if there is a loud noise (such as thunder or a car hom)? If you speak normally to your child, does he or she turn to look at you? Does any family member have a hearing problem? If any question above is answered positively for hearing loss, subject goes to second stage.

To screen subjects for hearing loss

To confirm diagnosis of hearing loss

To identify causes of hearing loss To ascertain genetic cases To determine inheritance modes

gated in this survey. In terms of hearing loss, special emphasis was placed on I) identifying the presence or absence of hearing loss and 2) ascertaining the age at which the hearing deficit was noticed by the patient or by his or her parents, as well as the age at which the problem was diagnosed. The questionnaire used for hearing screening is shown in Table 2. The examinations designed to screen for hearing loss in this stage included whispered voice testing (>6 years of age) and behavioral tests «6 years of age). In the second stage, patients in whom hearing loss was suspected were referred to otologists and other specialists (including a pediatrician, an obstetrician, an ophthalmologist, a dermatologist, a neurologist, a surgeon, and an internist) to evaluate the causes of hearing loss and to identify associated organ abnormalities. This entailed a careful history-taking, clinical investigations, and laboratory tests that would indicate exogenous factors or identify a genetic cause. A detailed history regarding age at onset and knowledge of pathogenesis (infection, drugs, etc) was obtained. Nonaudiological examinations included triiodothyronine and thyroxine levels, urine tests for proteinuria and hematuria, electrocardiography, skull radiography, and chromosomal analysis. The last stage involved investigating patients in whom no environmental factors were identified that would be responsible for hearing impairment. A detailed medical history was obtained, with an emphasis on a family history of hearing loss and other associated congenital anomalies, and a pedigree including at least 3 generations was established. Routine otologic examinations (including pure tone and oto-immittance audiometry) and physical examinations were carried out on all available family members. Finally, a segregation analysis as described by Vogel and Motulsky 7 was applied to determine the inheritance modes of hearing loss in these patients. In our study,



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TABLE 3. DISTRIBUTION OF HEARING LOSS BY AGE IN 4,164 CASES

TABLE 5. PREVALENCE OF HEARING LOSS IN DIFFERENT ETHNIC GROUPS

No. With Hearing Loss

Prevalence

Ethnic Group

Total No. Examined

Han (Chinese) Yi Tibetan Lisu Others

116,534 2,964 2,933 1,968 2,477

3,726 164 129 95 50

3.20 5.53 4.40 4.83 2.02

Patients With Hearing Loss Age (y)

Total No. Examined

8,915 0-4 5-9 8,826 10-14 16,416 Total children 34,157 15-29 38,231 30-44 26,613 16,454 45-59 11,421 60+ Total adults 92,719 Total 126,876

No. of Cases

Prevalence Percentage

(%)

20 57 150

0.48 1.37 3.60

0.22 0.65 0.91

511 953 1,008 1,465

12.27 22.89 24.21 35.18

1.34 3.58 6.12 12.83

4,164

100.00

3.28

the proportion of autosomal recessive (AR) to autosomal dominant (AD) nonsyndromic cases in the genetic group was determined by segregation analysis. This statistical technique estimates the segregation ratio, proportion of sporadic cases, and ascertainment probability. This method assumes complete ascertainment, which is appropriate because all affected individuals in the referral sites were ascertained. Analysis o~ multiplex sibships (more than 1 affected sibling) with unaffected parents gave a segregation ratio of 0.27.±0.07, compatible withAR inheritance. The proportion of nongenetic cases was estimated from the proportion of simplex (1 affected) to multiplex families.f

Audiological Assessment. Pure tone audiometry (Danplex AS 72 audiometer, air conduction and bone conduction with masking, if necessary) was undertaken whenever possible. Air conduction thresholds were measured at 250 and 500 Hz and at 1 2 6 and 8 kHz. Bone conduction thresholds were d~te~ined to identify the type of hearing loss. Oto-immittance measurements were carried out in some patients, and all were examined otoscopically. Individuals with a hearing loss averaging 27 dB hearing level (HL) or more in the better ear across 500, 1,000, 2,000, and 4,000 Hz were regarded as affected. The degree of hearing loss was examined in terms of mean values across the frequency range. The degree of loss was divided into the following categories: less than 55 dB HL, 56 to 90 dB HL, and more than 90 dB HL. Sensorineural hearing loss was defined as an air-bone TABLE 4. PREVALENCE OF HEARING LOSS IN DIFFERENT GEOGRAPHIC AREAS

Geographic Area Flatlands Hills Mountains

Total Subjects Examined 33,597 52,107 41,172

No. With Hearing Loss 1,291 1,541 1,332

Prevalence (%)

3.84 2.96 3.24

(%)

gap of less than 15 dB averaged over 0.5, 1, and 2 kHz. Conductive hearing loss was defined as normal bone conduction thresholds «20 dB) and an air-bone gap of greater than 15 dB averaged over 0,5, 1, and 2 kHz. Mixed hearing loss was diagnosed if there was a more than 20-dB HL bone conduction threshold, together with a IS-dB air-bone gap averaged across 0.5, 1, and 2 kHz. RESULTS

In total, 126,876 persons (63,741 male and 63,135 female) were investigated, representing 96% of the population in the referral sites. To evaluate the first stage of the screening protocol, we invited all subjects from the first referral site to undergo all of the tests from the first stage to the third stage.v Analysis of the resultin~ data showed that the initial screening test for hearmg loss had a sensitivity of 87.5% and a specificity of 93.3%. Among the 126,876 people screened at the first stage, 4,164 were identified as having hearing loss. The overall prevalence was 3.28% of the general population, with no significant difference between male (3.34% or 2,191 of 63,741) and female (3.13% or 1,973 of63,135; p > .05) subjects. The distribution of various ages for the 4,164 cases is shown in Table 3. The prevalence of hearing loss increases with age. The prevalences in various geographic areas and different ethnic groups are shown in Tables 4 and 5, respectively. The hearing loss was sensorineural in 73.03% of patients (3,041 of4, 164), conductive in 20.39% (849), and mixed conductive and sensorineural in 6.58% (274). The hearing loss was bilateral in 74.5% (3,103) and unilateral in 25.5% (1,061). The distribution and prevalences of degrees of hearing loss can be seen in Table 6. The prevalence of hearing loss was 0.67% TABLE 6. DISTRIBUTION OF HEARING LOSS BY SEVERITY IN 4,164 CASES

Hearing Threshold (dB)

No. of Cases

90 Total

2,656 1,272 236 4,164


Percentage Prevalence (o/c) 63.79 30.54 5.67 100.00

2.09 1.00 0.19 3.28

Liu et al, Epidemiology of Hearing Loss TABLE 7. DISTRIBUTION OF CAUSES IN 4,164 PATIENTS

Cause

No. of Cases

TABLE 8. DISTRIBUTION OF CAUSES OF HEARING LOSS IN CHILDREN AND ADULTS

Prevalence Percentage

Environmental 3,156 Presbycusis 1,563 Sequelae of otitis media 1,034 Noise-induced 227 Ototoxicity 121 Infections 84 Trauma 47 Sudden onset 17 Ear malformation 15 Others 48 Genetic 349 Autosomal recessive (nonsyndromic) 216 Autosomal dominant (nonsyndromic) 105 Otosclerosis 10 Familial ototoxicity 9 X-linked 5 Usher's syndrome 2 Waardenburg's syndrome I Pendred's syndrome I Chromosomal defects 3 Unknown 656 4,164 Total

(%)

75.80 37.54 24.83 5.45 2.91 2.02 1.13 0.41 0.36 1.15 8.38

2.49 1.23 0.82 0.19 0.10 0.07 0.04 0.01 0.01 0.04 0.28

5.19

0.17

2.52 0.24 0.22 0.12 0.05 0.02 0.02 0.07 15.75 100.00

0.08 0.008 0.007 0.004 27 dB for the average across the frequencies 0.5 to 4 kHz) are 665 per 100,000 and 281 per 100,000, respectively. That these prevalences are much higher than those ofWestern countries can be attributed to different criteria for hearing loss and to a higher prevalence in China of hearing loss due to otitis media. In the present series, there was a difference in prevalence among various types of hearing loss, with the highest prevalence being 2.4%, for sensorineural hearing loss. In the child group, the prevalence of conductive hearing loss (3.84%) was significantly higher than that of sensorineural hearing loss (2.58%; p < .05). Conductive hearing loss was identified in only 17.6% of adult cases, but was identified in 61.2% of child cases. These differences may reflect the fact that children are more susceptible to the factors that can cause damage to the middle ear and that conductive hearing loss is the main type of hearing impairment in children in China. For most patients (63.79% ), the degree of hearing loss is less than 55 dB HL. Only 5.67% of patients had a hearing loss of more than 90 dB HL. There have been many population-based surveys concerning the prevalence of hearing loss as a function of age, gender, hearing levels, and social class, but few reports offer the prevalence of genetic hearing impairment. In the current survey, special attention was focused on identifying genetic hearing loss at the time the data were collected and during their analysis (see Methods). The overall prevalence of genetic hearing loss was 275 per 100,000, with a high prevalence of nonsyndromic AR hearing loss (170 per 100,000; Table 7). This high prevalence may be explained in part by the high incidence of consanguinity in some population groups. Overall, consanguinity was documented in 7.4% of the AR group in this study. An estimate of the incidence of genetic hearing loss in childhood of 123 per 100,000 was obtained from this survey, which is somewhat higher than the prevalence of 88 per 100,000 claimed in the first decade of life in an age-matched population-based study. 12 To our knowledge, no epidemiological in-

formation is available on the prevalence of genetic hearing loss in adult populations, largely because of the lack of large-scale genetic-epidemiological surveys. In this study, the prevalence of genetic hearing impairment in the adult population (~15 years) was 335 per 100,000, which is higher than that in children. This result is not surprising, because genetically determined hearing impairment can develop at any age throughout life, either as the sole manifestation of the mutant genes or as part of an inherited syndrome. 13 Among syndromic hearing losses, only Waardenburg's, Usher's, and Pendred's syndromes were identified (Table 7) - compatible with the fact that they are the most frequent syndromes that include deafness.l" In terms of chromosomal defects, Down syndrome was diagnosed in 3 cases, for a prevalence of 2.37 per 100,000. Presently, there are few reports on the prevalence of hearing impairment in different geographic areas and among different ethnic groups in China. Our results showed that the population located in the flat area appeared to have a higher prevalence of hearing impairment than did people who lived in the hills and mountains (Table 4). There also appeared to be differences in the prevalence of hearing loss among different ethnic groups in Sichuan. The 3 main minorities (Tibetan, Yi, and Lisu) presented a higher prevalence than did the Chinese Han (Table 5). The reasons for the differences between geographic areas and between ethnic groups are unclear.

Causes of Hearing Loss. A number of reports appearing over the years have addressed the causes of hearing impairment in populations throughout the world. 1,3,13 However, most of the studies were carried out in industrialized countries, and there is little information on the causes of hearing loss in the developing nations. In many surveys throughout the world, the proportion of various causes of hearing impairment varies among populations. IS Probably the most important reason is the difficulty of obtaining appropriate etiologic data, arising from a lack of worldwide consensus on protocols for investigation and diagnosis. In addition, making accurate judgments about the etiologic effect of genetic factors in hearing impairment is not easy, because there is no uniform clinical terminology or set of criteria for genetic hearing loss. In our investigation, the cause of hearing impairment was clarified in 84.25% of cases; in 15.75%, the etiologic factors were unknown. As shown in Table 7, the most common causes of hearing impairment in the general population of China are presbycusis, otitis media, and genetic factors. An etiologic analysis of a profoundly deaf group has been published


Liu et ai, Epidemiology of Hearing Loss

showing genetic factors (43%) and infectious diseases (31 %) as the main causes.l'' Most conductive or mixed hearing loss (94.2% in children, 92.58% in adults) results from chronic suppurative otitis media and otitis media with effusion, from which most adult patients suffered in childhood. Among other infectious diseases, high fever (defined as hearing loss without identified cause after high fever), meningitis, and measles were other significant causes (Table 7). The proportion of middle ear infection in various age groups may reflect etiologic differences between developed countries and developing countries. In China, there is surprisingly little mention of the etiologic effect on hearing of viral factors such as congenital rubella, which is cited as a significant cause of congenital deafness. 14,15 One of the probable reasons is that few deaf children take routine serologic tests for the virus in China. However, as shown in a study on the prevalence of congenital profound deafness in this population, certain environmental factors (such as rubella) would contribute to the differences in prevalence related to different ages and seasons. 17 In our survey, presumably, cases that resulted from congenital viral infections might have been placed in the "unknown" category. It is hard to carry out a direct comparative analysis of the proportion of genetic hearing loss between 2 studies because of the wide range in criteria, definition of samples, age of subjects, and hearing levels. The estimates of the proportion of cases with genetic hearing impairment vary widely, from 3% to 78% in adults and childrenl-' and from 9% to 54% in childhood.l'' The wide variation in the percentage of hereditary hearing loss may reflect true differences in genetic expression within the various target populations. However, it is possible that the etiologic effect of genetic factors in hearing impairment has been underestimated in the literature because of I) a lack of valid epidemiological data on genetic hearing loss; 2) difficulties in distinguishing genetic hearing impairment from acquired impairment audiologically!"; and 3) the poor specificity and low sensitivity of routine audiological methods for screening the carriers of genes that cause hearing impairment.w-J There have been few surveys in China to evaluate the etiologic effects of genetic factors. In the present study, inherited hearing impairment accounted for 20.98% of the adults with sensorineural hearing loss (excluding presbycusis) and 42.6% of the children with sensorineural hearing loss. The most common forms of genetic hearing impairment were the AR forms, accounting for 62.75% of cases, and AD forms, accounting for 33.24%. X-linked inheritance was found in 1.43%, and mitochondrial transmission in

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2.58%. In another study, only 5.94% of genetically determined profound hearing loss was the AD form. 16 The high proportion of the AD mode in the current study can be attributed to the fact that cases of hearing loss ranging from mild to profound were included. Recent advances in molecular biology and genetics have made possible the isolation, sequencing, and characterization of genes that cause hearing impairment. This will provide a basis for better understanding of the molecular biochemistry and development of the auditory system. The genes for several of the most common genetic syndromes that include deafness (Waardenburg's, Usher's, and Pendred's syndromes) have been identified.V There has been substantial recent progress in nonsyndromic hearing loss, with more than 50 loci having been mapped from various populations around the world. 23 Moreover, 2 forms of genetic deafness are much more frequent than the others, accounting for at least 30% of all genetic cases in many populations. One of these genes, the connexin 26 locus (Cx26), has been found to be a major cause of nonsyndromic AR deafness in many populations.P Most interestingly, a single mutation in the connexin 26 gene, 35delG, accounts for the majority (60% to 80%) of mutant Cx26 alleles in families with nonsyndromic deafness in the United Kingdom, France, Italy, Spain, Tunisia, Lebanon, Australia, Russia, and New Zealand. The second most common form of genetic deafness is the A 1555G substitution in a mitochondrial ribosomal RNA gene, which causes increased susceptibility to aminoglycos ide antibiotic-induced deafness, as well as nonsyndromic hearing loss.24 The mitochondrial DNA (mtDNA) Al555G mutation has been reported in many ethnic groups, with more than 20% of deaf individuals carrying this mutation in some populations. 23 So far, there have been no reports regarding Cx26 mutations and mtDNA Al555G mutation or the prevalence of the 35deiG mutation in large samples of Chinese patients with nonsyndromic hearing loss. At least 8 different loci were responsible for AR profound deafness in the present population on the basis of the calculation of heterogeneity. 17 Recently, 2 Chinese families with nonsyndromic AR deafness from the current population were identified as carrying mutations in the myosin VIlA gene. 25 More recently, we have started to perform mutation analysis of the 2 most common mutations in a large number of probands with nonsyndromic hearing loss from this population. We found that 30% of the probands carried the mtDNA Al555G mutation. Surprisingly, the 35deiG mutation in Cx26 was not found in any of these cases (Liu et al, unpublished data). A variety of commonly used drugs have ototoxic properties. The most common ototoxic drugs in China



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are aminoglycoside antibiotics (such as streptomycin, kanamycin, and gentamicin). The incidence of aminoglycoside-induced deafness has increased in recent years and is one of the major causes of hearing impairment in China. Some investigations based in schools for the deaf have indicated that 12.8% to 66.1 % of cases of profound deafness resulted from aminoglycoside antibiotics, with a population prevalence of 0.035%.9 In our survey, the prevalence of drug-induced deafness was 0.103% and accounted for 8.8% of sensorineural hearing loss (excluding presbycusis) and for 20.45% of sensorineural hearing loss in children. Among the 130 cases of pharmacological ototoxicity, 6.92% had a positive family history, yielding a prevalence of recognizable familial cases of 0.007%. The matrilineal transmission of aminoglycoside-induced deafness in the Chinese population was first reported in isolated pedigrees in the early 1990s, and mutations in the mtDNA were suggested as the likely cause. 26 .27 The identification of the mtDNA A1555G mutation in a large proportion of families with nonsyndromic deafness in our sample provides a molecular explanation for the high prevalence of aminoglycoside-induced hearing loss in the Chinese population. Presbycusis, the hearing loss associated with aging, is the most common etiologic form of hearing loss in all studied populations. It affects more than 27% of persons over the age of 65 years and 50% of those 80 years of age or 0Ider.2,4 Because of the lack of worldwide diagnostic criteria for presbycusis and difACKNOWLEDGMENTS -

ferent socioeconomic conditions, we defined cases as presbycusis using the following criteria: 1) age of hearing impairment greater than 55 years; 2) symmetric bilateral sensorineural hearing loss without known causes; and 3) negative family history of hearing loss. In the present study, presbycusis accounted for 37.54% of all cases, and affected 9.99% of those more than 55 years of age. CONCLUSION

Individuals with hearing impairment were investigated in the general population of Sichuan. The total prevalence (3.28%) of hearing impairment obtained from this study is significantly lower than that in industrialized nations, but the prevalence in children (0.665%) is significantly higher than that in reports from Western countries, mainly because of a higher prevalence of otitis media in China. There is a significant difference in the proportion of the types of hearing loss between children and adults. The prevalences of genetic hearing loss in children (0.11%) and in adults (0.33%) were higher than those in previous reports. The high proportions of infections in the middle ear and aminoglycoside-induced hearing loss reflect differences in causes of hearing impairment between developed countries and developing ones. Presbycusis and sequelae of otitis media were the main causes of hearing impairment in adults; otitis media and genetic factors were the main causes in children. It is suggested that the effect of genetic factors in the general population should be emphasized.

We thank all of the medical personnel from the II prefectures of Sichuan who aided in the field, clinical, and

laboratory work.

REFERENCES I. Davis AC. Hearing disorders in the population: first phase findings of the MRC National Study of Hearing. In: Lutman ME, Haggard MP, eds. Hearing, science and hearing disorders. New York, NY: Academic Press, 1983:35. 2. Dawson DA. National Center for Health Statistics: current estimates from the National Health Interview Survey, 1989. Vital and Health Statistics, Series 10. No. 176. 3. Davidson J, Hyde ML, Albert pw. Epidemiology of hearing impairment in childhood. Scand Audiol 1988;30:13-20. 4. Davis AC. The prevalence of hearing impairment and reported hearing disability among adults in Great Britain. Int J EpidemioI1989;18:911-7. 5. Davis AC, Parving A. Towards appropriate epidemiology data on childhood hearing disability: a comparative European study of birth-cohorts 1982-1988. J Audiol Med 1994;3:35-47. 6. Zhang SL, Tang XD, Zhang SZ. Genetico-epidemiological survey of the general population in Sichuan. Chengdu, China: CST University Press, 1990: 10-58. 7. Vogel F, Motulsky AG. Human genetic problems and approaches. New York, NY: Springer-Verlag, 1979:530-98. 8. Liu XZ, Xu LR. Sensorineural hearing loss: a segregation analysis. J Chin Med Genet 1988;5: 193-5.

9. Hu DN, Qiu WQ, Wu BT, et al. Prevalence and genetic aspects of deaf mutism in Shanghai. J Med Genet 1987;24:58992. 10. Jiang SZ, Wang SL, Liu PI. The survey of hearing loss in Nangton County, China. Chin J Otolaryngol 1988;23:282-3. II. Parving A, Hein HO, Suadicani P, Ostri B, Gyntelberg F. Epidemiology of hearing disorders: some factors affecting hearing. The Copenhagen male study. Scand Audiol 1993;22: 101-7. 12. Parving A. Hearing disability in childhood - a crosssectional and longitudinal investigation of causative factors. Int J Paediatr Otorhinolaryngol 1993;27: 101-11. 13. Gorlin RJ. Genetic hearing loss with no associated abnormalities. In: Gorlin RJ, Toriello HV,Cohen MM, eds. Hereditary hearing loss and its syndromes. Oxford, England: Oxford University Press, 1995:43-61. 14. Fraser GR. The causes of profound deafness in children. Baltimore, Md: Johns Hopkins University Press, 1976. 15. Williamson I, Steel K. The aetiology of hearing impairment. Hereditary Deafness Newsletter 1990;5:7-/6. 16. Liu XZ, Xu LR, Zhang SL, Xu Y. Prevalence and aetiology of profound deafness in the general population of Sichuan, China. J Laryngol Otol 1993; 107:990-3.


Liu et ai, Epidemiology of Hearing Loss 17. Liu XZ, Xu LR, Zhang SL, Xu Y. Epidemiological and genetic studies of congenital profound deafness. Am J Med Genet 1994;53: 192-5. 18. Parving A. Epidemiology of genetic hearing impairment. In: Martini A, Read A, Stephens D, eds. Genetics and hearing impairment. London, England: Whurr Publishers, 1996:73-81. 19. Liu X, Xu L. Nonsyndromic genetic deafness: an analysis of audiograms. Ann Otol Rhinol Laryngol 1994; 103:428-33. 20. Meredith R, Stephens D, Sirimanna T, Meyer-Bisch C, Reardon W. Audiometric detection of carriers of Usher's syndrome type II. J Audiol Med 1992; I: 11-9. 21. Liu XZ, Newton VE. Distortion product emissions in normal-hearing and low-frequency hearing loss carriers of genes for Waardenburg's syndrome. Ann Otol Rhinol Laryngol1997; 106:220-5. 22. Steel K, Brown SDM. Genetics of deafness. Curr Opin

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NeurobioI1996;6:520-5. 23. Van Camp G, Smith RJH. Hereditary hearing loss homepage. Available at: http:dnalab-www.uia.ac.be/dnalab/hhh/.Accessed 1999. 24. Prezant TR, Agapian JV, Bohlmann MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibioticinduced and non-syndromic deafness. Nat Genet 1993;4:28994. 25. Liu XZ, Walsh J, Mburu P, et al. Mutations in the myosin VIlA gene cause non-syndromic recessive deafness. Nat Genet 1997;16:188-90. 26. Liu XZ, Xu LR, Yang S. Aminoglycoside-induced hearing loss: a mitochondrial inheritance. Hereditary Deafness Newsletter 1991;6: 18. 27. Hu DN, Qiu WQ, Wu BT, et al. Genetic aspects of antibiotic induced deafness: mitochondrial inheritance. J Med Genet 1991;28:79-83.
