Education in the genetics of hearing loss: a survey of early hearing detection and intervention programs.

PURPOSE: Permanent hearing loss at birth or in early childhood is common and has many genetic and environmental causes. Advances in the identification and characterization of genetic forms, combined with the early identification of children through the implementation of state-based Early Hearing Detection and Intervention programs suggests the need for education about the causes of hearing loss among professionals who work in these programs. METHODS: An online survey was directed to state program coordinators of Early Hearing Detection and Intervention programs to identify gaps in knowledge about the genetic causes of hearing loss and to assess interest in continuing education on this topic. RESULTS: The study identified clear gaps in respondents' knowledge about genetic causes of hearing loss. Twenty percent of respondents indicated that they had received no training in genetics. When asked to rate their knowledge about the genetics of hearing loss, most rated their knowledge as "not adequate." Respondents expressed interest in genetics training through several modalities, including a distance learning format. CONCLUSION: This study provides documentation of the need for education of health care professionals involved in the early identification of hearing loss. Suggestions for suitable educational formats based on respondent needs and interests are provided.     

Outcomes of clinical examination and genetic testing of 500 individuals with hearing loss evaluated through a genetics of hearing loss clinic

Hearing loss (HL) occurs in approximately 2 out of every 1,000 births and is genetic in origin in approximately 50% of cases. This high incidence coupled with the increasing number of genes implicated in HL and the trend toward universal newborn screening led to the establishment of the Genetics of Hearing Loss Clinic at The Children's Hospital of Philadelphia to manage the diagnosis, genetic screening, and counseling of families with an affected child. To date 500 individuals have been evaluated from 1999 to 2004. To determine the cause of their HL and screen for syndromic forms of HL, individuals were offered a panel of tests. Depending on the type and severity of the HL, recommendations included GJB2 mutation analysis, renal and thyroid function studies, a CT scan of the temporal bones, an ophthalmology evaluation, an EKG, and, at times, additional genetic tests. Of the 500 patients evaluated 70 (14%) had a syndromic etiology for their HL. Twenty-eight different syndromic etiologies were identified. Enlarged vestibular aqueducts (EVAs) and/or Mondini malformations were seen in 18% of individuals with HL who had a CT or MRI of the temporal bones. Genetic testing of the GJB2 gene was completed for 310 of the 377 patients with bilateral sensorineural HL (82.2%). Nineteen different variants were identified in the GJB2 gene. Through GJB2 mutational analysis, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 110/500 (22%) of patients.     

Ageing and hearing loss

Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved.     

新生儿及疑似听力障碍儿童听力筛查的病例分析

目的1.收取本地区新生儿听力障碍发病资料;2.分析听力筛查未通过的因素及临床听力学特征。方法选取2006年5月至2007年5月出生的286例新生儿,在出院前进行新生儿听力筛查;96例转诊至我科的疑似听力障碍患儿进行诊断性听力学检查。对未通过者进行声阻抗、耳声发射、听性脑干反应、听觉稳态诱发反应全面的综合检查以确定听力损失的性质和程度,给予相应干预措施。结果286例新生儿,其中初筛有40例（13.99%）未通过筛查,42天复筛DPOAE,最后有3例需行ABR检查,经过听力学初步评估发现2例（发病率为6.99‰）有听力损失,其中正常新生儿1例（发病率为3.94‰）,高危新生儿1例（发病率为31.25‰）并作相应诊断和干预;转诊疑似听力损失患儿96例,确认听力损失78例（81.25%）,其中轻度2例（2.5%）、中度7例（9.0%）、重度25例（32.1%）、极重度44例（56.4%）,发现确诊年龄在6个月～3岁范围内。结论3个月内早期诊断和6个月内早期干预是必要的,以便尽早发现患儿及时给予干预。推行新生儿及婴幼儿听力损失的早期筛查和干预,加强耳聋知识的宣传,提高家长的防聋治聋意识是非常必要的。     

A multi-channel hearing prosthesis for profound-to-total hearing loss

A multi-channel cochlear implant hearing prosthesis providing 22 separate channels of stimulation has been developed. The electronics for the implantable receiver-stimulator have been incorporated on a single chip, using digital circuits and employing CMOS technology. The chip is enclosed in a titanium capsule with platinum/ceramic electrode feed-throughs. A pocket-sized speech processor and directional microphone extract the following speech parameters: signal amplitude, fundamental frequency and formant frequency. The fundamental frequency is coded as electric pulse rate, and formant frequency by electrode position. The speech processor has been realized using hybrid circuits and CMOS gate arrays. The multi-channel prosthesis has undergone a clinical trial on four postlingually deaf patients with profound-total hearing losses. The speech perception results indicate that they were able to obtain open-set speech recognition scores for phonetically balanced words, CID sentences and spondees. In all cases the tests showed significant improvements when using the cochlear prosthesis combined with lipreading compared to lipreading alone.     

Congenital cytomegalovirus infection and hearing loss

Sensorineural hearing loss is the most frequent sequela of congenital cytomegalovirus (CMV) infection, and epidemiological evidence also suggests that congenital CMV infection is responsible for a substantial proportion of sensorineural hearing loss in children. Hearing loss due to congenital CMV infection can be present at birth or can appear later, usually during the first year of life; it usually worsens as the infant or child ages. Follow-up of children with congenital CMV infection should include repeated audiological testing. Based on the benefits of early detection of hearing loss, one could propose screening all infants for congenital CMV infection so that those with hearing impairment can be identified as early as possible by appropriate audiological follow-up. Antiviral treatment that could improve hearing outcome, with a safety profile suitable for use in minimally ill infants, would clearly increase the benefit of universal screening for congenital CMV infection.     

Maternally inherited nonsyndromic hearing loss

In this study we characterized clinically and evaluated molecularly a large family with maternally inherited hearing impairment. Relatives were evaluated audiologically and clinically, the most likely pattern of inheritance was deduced, and molecular DNA analysis for the known mitochondrial mutations associated with hearing impairment was performed. Clinical examination of several relatives showed a normal general state of health, but in 14 of the members tested variable degrees of sensorineural hearing loss were noted. The pedigree was established and demonstrated a clear pattern of maternal inheritance, with 34 of 38 offspring of deaf mothers being hearing impaired, but none of 22 offspring of deaf fathers having any hearing impairment. Since by far the most likely explanation of such a maternal inheritance pattern is a mitochondrial mutation, molecular testing for the three known mitochondrial mutations, A1555G, A7445G, and Cins7472, was performed on 27 of the relatives. All of the individuals tested had the normal sequence at the sites tested. This family with nonsyndromic sensorineural hearing loss has an inheritance pattern strongly suggestive of a mitochondrial mutation. However, molecular testing for the three known mitochondrial mutations associated with nonsyndromic hearing impairment was negative, implying that additional molecular defects can lead to the same phenotype. The search for this novel molecular defect is underway. Am. J. Med. Genet. 84:369–372, 1999. © 1999 Wiley-Liss, Inc.     

Autosomal recessive nonsyndromic hearing loss

Nearly all genes for autosomal recessive nonsyndromal inherited hearing loss (ARNSHL) localized thus far cause prelingual severe to profound or profound hearing impairment. Of the 25 reported loci, most have been identified using single consanguineous families. Six of these genes have been cloned and encode a variety of proteins, including ion channels, extracellular matrix components, cytoskeletal components, and proteins essential for synaptic vesicular trafficking. One of these genes appears to be responsible for approximately 50% of all congenital severe to profound or profound hearing loss in many world populations, and mutations in two other genes can lead to either syndromic or nonsyndromic forms of deafness. The identification of additional genes that cause ARNSHL and elucidation of their function will refine our understanding of auditory physiology at the molecular level.     

Molecular mechanisms of age-related hearing loss

Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with aging and is the most common cause of adult auditory deficiency in the United States. Presbyacusis is defined as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. This condition affects approximately 23% of the population between 65 and 75 years of age and 40% of the population older than 75 years of age. In 1980, it was estimated that 11% of the population was 76 years or older and this number is expected to nearly double by the year 2030 [, Otolaryngol. Head Neck Surg. 100, 262]. When coupled with the fact that the population over 65 years of age is experiencing the most rapid progression of hearing loss, the potential socioeconomic ramifications are staggering. Interestingly, presbyacusis varies in its frequency across differing societies. This discrepancy has been attributed to many factors such as genetics, diet, socioeconomic factors, and environmental variables [, Otolaryngol. Head Neck Surg. 100, 266;. Scand. Audiol. 26 (1997) 133]. The purpose of this discussion is to illuminate the various molecular mechanisms underlying this age-related hearing loss and to offer insights into potential ways to mitigate the effects of aging on hearing impairment.     

Mixed hearing loss in Larsen Syndrome

A mixed bilateral hearing loss is described in a child with classical Larsen syndrome. The presence of a residual conductive loss after successful placement of ventilating tubes suggests that the conductive loss is due to an ossicular abnormality. In Larsen syndrome, characterized by multiple joint dislocations and bony malformations, the ossicular joints may also be affected.     

Susceptibility of the sympathectomized ear to noise-induced hearing loss

Unilaterally sympathectomiced rats were exposed to 100 dB L_eq frequency-modulated noise for I month. Normotensive as well as spontaneously hypertensive animals (with a blood pressure of above 200 mmHg) were investigated. Auditory sensitivity was determined by auditory brainstem responses to 1/3-octave filtered sine waves in the frequency range 0.8–20.0 kHz. In addition, a morphological analysis was carried out. It was found that the sympathetic innervation to the inner ear of the rat originated in, or passed through the ipsilateral superior cervical ganglion. Sympathectomy did not alter pre-exposure hearing thresholds nor influence the size of the noise-induced hearing loss either in 3 or 11 months old hypertensive rats, or in normotensive rats of 11 months. A slightly smaller loss was seen in the sympathectomized side in young normotensive rats. It was concluded that the sympathetic does not exert a protection of the inner ear against functional disturbances in hypertension, neither during basal metabolic condition nor during extreme conditions, i.e. during noxious noise exposure.     

感音神经性耳聋分子机制的研究进展

感音神经性耳聋主要表现为声波感受障碍引起的听力损失,与耳蜗感觉上皮和螺旋神经元的结构及功能受 损密切相关,但具体的病理机制尚不确切。细胞、分子水平的研究证明细胞凋亡、氧化应激损伤、免疫炎症、代 谢障碍、基因突变可能参与多种因素引起的内耳细胞损伤或死亡,引起听力损失。本文将围绕上述细胞、分子过 程在多种因素引起的感音神经性耳聋内耳细胞损伤和存活中的调控机制进行综述,以帮助研究人员识别关键分子 靶点,为干预、治疗感音神经性耳聋新策略提供参考。