Congenital Hearing Impairment Research Articles

Neonatal hearing screening model: An Italian regional experience

Objective. To produce a model for routine centralized hearing screening including all aspects of the screening, from diagnosis to psychological counseling and early rehabilitation.Methods. A prospective observational study on a geographically defined pediatric population (Liguria region, northwestern Italy) and data collection in a data bank. The model proposed was created for the audiological screening of all newborns of the Liguria region. The model includes four phases: (1) preliminary identification of contractual, administrative, legal aspects; (2) screening for identification of congenital hearing impairment; (3) therapy and rehabilitation of identified subjects and genetic analysis; (4) epidemiology, data management, and workload management. To test the feasibility of the model proposed and to establish the workload required according to the resources available in the regional health plan, we performed a pilot study on all infants born in four of the 13 regional birth centers of Liguria region from 1 April 2001 to 30 September 2001.Results. Out of the 3268 newborns enrolled during the 6-month pilot study, 3238 (99.1%) were screened with otoacoustic emissions (OAE), while screening was refused in 30 newborns (0.9%). OAE resulted in a ‘pass’ for 3180 newborns (98.2%) and a ‘refer’ in 58 (1.8%). The standard auditory brainstem response (ABR) test was performed in 156 newborns, 58 of them as a result of the ‘refer’ at the second OAE and 98 others at audiological risk. Results were positive or uncertain at first ABR in 45 patients. Workload was calculated on the basis of the data obtained in the pilot study to allocate financial and organizational resources.Conclusions. The results of the pilot study allowed project planning. We think that the screening model proposed is an example of how a regional organization can deliver improved quality care through a rationalization and optimization process.

Myosin-7A Mutation Screening in Patients with Prelingual Non-Syndromic Hearing Impairment

ObjectiveTo screen for mutations in myosin-7A gene (MYO7A) in patients with prelingual nonsyndromic hearing impairment. Methods 31 sporadic patients with congenital hearing impairment and 65 patients from 34 families with prelingual hereditary hearing impairment in China were tested in this study, and 100 hearing normal individuals were used as control. Genomic DNA isolated from whole blood of all subjects was subjected to polymerase chain reaction(PCR) to amplify selected exons of MYO7A gene. The PCR products were subsequently screened using single strand conformational polymorphism analysis(SSCP) and direct sequencing when the fragments showed an abnormal electrophoretic pattern. ResultsGgA transition at position 617 in exon 7, which would produce an A206G amino acid substitution, was detected in two patients but in none of the unaffected members in the families. This heterozygous missense mutation happened within a highly conserved heptapeptide sequence of MYO7A protein, and is closely relevant to preligual nonsyndromic deafness. ConclusionsThe A206G substitution is possibly a new mutation to cause preligual nonsyndromic hearing impairment. Our results provide evidence that exon 7 of MYO7A is a mutational hotspot in genetic hearing impairment.

GJB2 mutation spectrum in deaf population in a typical southeastern area of China

Mutations inGJB2gene are the most frequently found mutations in patients with nonsyndromic hearing impairment. However, the spectrum and prevalence of mutations in this gene vary among different ethnic groups. In China, 30,000 infants are born with congenital hearing impairment annually. In order to provide appropriate genetic testing and counseling to the families, we investigated the molecular etiology of nonsyndromic deafness in 103 unrelated school children attending Nantong School for the Deaf and Mute in Jiangsu Province, China. The coding exon of theGJB2gene was PCR amplified and sequenced. Sixty twoGJB2mutant alleles were identified in 35.9% (37/103) of the patients. Twenty five patients carried two pathogenic mutations and 12 patients carried one mutant allele. The 235delC was the most common mutation accounting for 69.4% (43/62) ofGJB2mutant alleles. TheGJB2mutant alleles accounted for 30.1% (62/206) of all chromosomes responsible for nonsyndromic hearing impairment. Testing of the 3 most prevalent deleterious frame shift mutations in this cohort detected 100% of allGJB2mutant alleles. These results demonstrate that an effective genetic testing of GJB2 gene for patients and families with nonsyndromic hearing impairment is possible.

Neonatal hearing screening: modelling cost and effectiveness of hospital- and community-based screening

BackgroundChildren with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values.MethodsDesign: Clinical effectiveness analysis using a Markov Model. Outcome measure: quality weighted detected child months (QCM).ResultsBoth hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of £3,690,000 per 100,000 screened children in hospital and £3,340,000 in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community.ConclusionThis modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings.

Brainstem auditory evoked potentials in the diagnosis of congenital hearing impairment

Brainstem auditory evoked potentials in the diagnosis of congenital hearing impairment

Usher syndrome with psychotic symptoms: Two cases in the same family

Usher syndrome is a heterogeneous autosomal recessive disorder characterized by hearing and visual sensory impairment. Retinitis pigmentosa is essential for its diagnosis. There are only a few reports describing patients with Usher syndrome presenting with psychotic features and the etiology of its psychiatric manifestation is still unknown. Herein, the authors report variable congenital hearing impairment and progressive visual loss occurring in five of seven family members and two of them meeting the diagnostic criteria of Usher syndrome with psychotic features. Furthermore, the authors compare their psychiatric symptoms with other reports and the possible etiologies of psychotic symptoms are discussed.

Postnatal Risk Factors of Congenital Hearing Impairment: Otitis Media, Head Injuries and Convulsions

KEYWORDS Sensorineural; hearing loss; Otitis media; congenital ABSTRACT Hearing impairment is the most prevalent sensory disability and is caused by a variety of genetic and environmental factors. Many studies have proposed otitis media, head injury, convulsions, respiratory problems and infections to the infants as the important antecedents of neonatal deafness or hearing impairment. A prospective etiological study of adverse postnatal conditions leading to bilateral sensorineural neonatal hearing impairment was conducted. In this study 1076 children below 14 years of age with congenital hearing loss were investigated. The results showed adverse postnatal history in 20.26% (218) of the cases out of 1076. High risk factors included otitis media, head injury and convulsions and respiratory distress. Majority (126/11.71%) of the cases showed otitis media followed by head injury in 4.83% (52) of the cases, convulsions in 2.78% (30) of the cases and respiratory problems in 0.92% (10) of the cases. It can be concluded that careful monitoring of the child during the first few years and vaccination against all the infections is necessary.

Mitochondrial 12S rRNA A827G mutation is involved in the genetic susceptibility to aminoglycoside ototoxicity

We have analyzed the clinical and molecular characterization of a Chinese family with aminoglycoside-induced and non-syndromic hearing impairment. Clinical evaluations revealed that only those family members who had a history of exposure to aminoglycoside antibiotics subsequently developed hearing loss, suggesting mitochondrial genome involvement. Sequence analysis of the mitochondrial 12S rRNA and tRNA Ser(UCN) genes led to the identification of a homoplasmic A827G mutation in all maternal relatives, a mutation that was identified previously in a few sporadic patients and in another Chinese family with non-syndromic deafness. The pathogenicity of the A827G mutation is strongly supported by the occurrence of the same mutation in two independent families and several genetically unrelated subjects. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly conserved in mammals. It is possible that the alteration of the tertiary or quaternary structure of this rRNA by the A827G mutation may lead to mitochondrial dysfunction, thereby playing a role in the pathogenesis of hearing loss and aminoglycoside hypersensitivity. However, incomplete penetrance of hearing impairment indicates that the A827G mutation itself is not sufficient to produce clinical phenotype but requires the involvement of modifier factors for the phenotypic expression. Indeed, aminoglycosides may contribute to the phenotypic manifestation of the A827G mutation in this family. In contrast with the congenital or early-onset hearing impairment in another Chinese family carrying the A827G mutation, three patients in this pedigree developed hearing loss only after use of aminoglycosides. This discrepancy likely reflects the difference of genetic backgrounds, either mitochondrial haplotypes or nuclear modifier genes, between two families.

Postnatal Risk Factors of Congenital Hearing Impairment: Otitis Media, Head Injuries and Convulsions

Postnatal Risk Factors of Congenital Hearing Impairment: Otitis Media, Head Injuries and Convulsions

Goitrous Congenital Hypothyroidism and Hearing Impairment Associated with Mutations in the TPO and SLC26A4/PDS Genes

Pendred syndrome (PS) and thyroid peroxidase (TPO) deficiency are autosomal-recessive disorders that result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and an iodide organification defect as common features. Whereas the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses. The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss, and PS was suspected. We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro. Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The mutant pendrin (p.R776C) retained its ability to transport iodide in vitro. These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.

The mapping of DFNB62, a new locus for autosomal recessive non‐syndromic hearing impairment, to chromosome 12p13.2‐p11.23

Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common form of prelingual inherited hearing impairment (HI). Here is described the mapping of a novel ARNSHI locus in a consanguineous Pakistani family with profound congenital HI. Two-point and multipoint linkage analyses were performed for the genome scan and fine mapping markers. Haplotypes were constructed to determine the region of homozygosity. At theta = 0, the maximum two-point LOD score of 4.0 was obtained at marker AAC040. A maximum multipoint LOD score of 5.3 was derived at marker D12S320, with the three-unit support interval demarcated by D12S89 and D12S1042. The region of homozygosity is flanked by markers D12S358 and D12S1042, which corresponds to 22.4 cM according to the Rutgers combined linkage-physical map of the human genome and spans 15.0 Mb on the sequence-based physical map. A novel ARNSHI locus DFNB62 was mapped to chromosome 12p13.2-p11.23. DFNB62 represents the second ARNSHI locus to map to chromosome 12.

The Economic Costs of Congenital Bilateral Permanent Childhood Hearing Impairment

The objective of this study was to estimate the economic costs of bilateral permanent childhood hearing impairment (PCHI) in the preceding year of life for children aged 7 to 9 years. A cost analysis was conducted by using a birth cohort of children born between 1992 and 1997 in 8 districts of Southern England, of which half had been born into populations exposed to universal newborn screening (UNS). Unit costs were applied to estimates of health, social, and broader resource use made by 120 hearing-impaired children and 63 children in a normally hearing comparison group. Associations between societal costs per child and severity of hearing impairment, language ability score, exposure to UNS, and age of confirmation were analyzed, including adjustment for potential confounders in a linear regression model. The mean societal cost in the preceding year of life at 7 to 9 years of age was 14092.5 pound sterling for children with PCHI, compared with 4206.8 pound sterling for the normally hearing children, a cost difference of 9885.7 pound sterling. After adjusting for severity and other potential confounders in a linear regression model, mean societal costs among children with PCHI were reduced by 2553 pound sterling for each unit increase in the z score for receptive language. Using similar regression models, exposure to a program of UNS was associated with a smaller cost reduction of 2213.2 pound sterling, whereas costs were similar between children whose PCHI was confirmed at <9 or >9 months. CONCLUSIONS. The study provides rigorous evidence of the annual health, social, and broader societal cost of bilateral PCHI in the preceding year of life at 7 to 9 years of age and shows that it is related to its severity and has an inverse relationship with language abilities after adjustment for severity.

SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations

Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.

Congenital hearing impairment

Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling. High-resolution CT and MRI have contributed to the evaluation and management of hearing impairment. In addition, with the identification of innumerable genetic loci and genetic defects involved in hearing loss, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment. Some of the common forms of congenital hearing loss are reviewed and their imaging features illustrated.

Role of intrauterine Rubella infection in the causation of congenital deafness

Background : Rubella is a contagious viral infection associated with rash. 10-15% of women are susceptible to this infection in their childbearing years and the disease is usually transmitted to the developing fetus causing abortion or stillbirth or congenital Rubella syndrome (CRS). Sensorineural hearing loss is one of the most common abnormalities associated with CRS. Aims : The study was undertaken to determine the prevalence of Rubella induced congenital deafness in south India. Materials and Methods : The present study is carried out on 1076 hearing impaired children below 14 years of age to determine etiological factors for congenital hearing impairment. Various audiometric tests such as PTA, OAE and BERA were carried out to know the type and degree of hearing impairment. Development histories including the prenatal, perinatal and postnatal histories were collected using a standard questionnaire. Results : The results indicated very less percentage (1.57%) of cases with the history of maternal Rubella infection indicating a significant reduction of Rubella-induced deafness in the developing countries. Conclusions : The main reason behind the low percentage of children with rubella- induced hearing impairment may be due to appropriate immunization of mothers to the rubella infection during their child bearing years. The increasing awareness in the developing countries of this infection and its consequences is another important reason behind the low percentage of the affected population.

Waardenburg syndrome

Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.

Usherin, the defective protein in Usher syndrome type IIA, is likely to be a component of interstereocilia ankle links in the inner ear sensory cells

Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing impairment and retinitis pigmentosa. It is the most common genetic form of USH. USH2A encodes usherin, which was previously defined as a basement membrane protein. A much larger USH2A transcript predicted to encode a transmembrane (TM) isoform was recently reported. Here, we address the role of TM usherin in the inner ear. Analysis of the usherin alternative transcripts in the murine inner ear revealed the existence of several predicted TM usherin isoforms with modular ectodomains of different lengths. In addition, we identified in the usherin cytoplasmic region a predicted 24 amino acid peptide, derived from a newly defined exon that is predominantly expressed in the inner ear but not in the retina. In mouse and rat inner ears, we show that TM usherin is present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. The usherin immunolabeling is transient in the hair bundles of cochlear hair cells (HCs), but persists in mature hair bundles of vestibular HCs. Several lines of evidence support the involvement of TM usherin in the composition of the ankle links, a subset of filamentous lateral links connecting stereocilia at the base. By co-immunoprecipitation and in vitro binding assays, we establish that the usherin cytodomain can bind to whirlin and harmonin, two PDZ domain-containing proteins that are defective in genetic forms of isolated deafness and USH type I, respectively. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. Our results strongly suggest that congenital deafness in USH type I and type II shares similar pathogenic mechanisms, i.e. the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles.

Evaluation of the Austrian Newborn Hearing Screening Program

Universal Neonatal Hearing Screening (UNHS) has been gradually implemented since the mid-nineties in Austrian maternity wards and neonatal intensive care units. This study evaluated the effect of UNHS on reducing age at identification as well as age of intervention for children with congenital and perinatal sensorineural hearing impairment. This was a retrospective analysis of clinical data of 394 Austrian children diagnosed with an at least mild degree (> 20 dB hearing level) of permanent sensorineural hearing loss. Age at identification and age at intervention were compared between children who underwent UNHS ('with UNHS') and those who did not undergo UNHS ('without UNHS'). The median of age of identification was 37.6 months in children without UNHS, and 3.9 months in children with UNHS. By six months of age, 69% of hearing-impaired children who underwent UNHS, were identified but only 6% of those without UNHS. At one year, the corresponding percentages are 80% and 12%, respectively. In children without UNHS, the degree of hearing loss was the most predictive factor of age at identification (median of age at diagnosis for profound hearing loss: 15 months; severe: 26 months; moderate: 52 months; mild: 73 months). In children with UNHS, age of identification was unrelated to degree of hearing loss (medians between 3.7 and 4.4 months). In the majority of children intervention began within one month after diagnosis, regardless of whether or not the child was identified by UNHS. UNHS greatly increases the proportion of children whose hearing impairment is diagnosed before six months of age. However, in some 20% of children, hearing impairment was diagnosed later than one year of age, despite having failed the screening. Additionally, data from this study suggest that about 15% of childhood hearing losses manifest themselves after the hearing screening period. Efforts are thus required for the early detection of these children as well.

Kongenitale Schwerhörigkeit

About 50% of congenital non-syndromic hearing impairment is caused by genetic factors. Research on the genetics of deafness has revealed a vast number of relevant genes. Mutations in the GJB2 gene have been shown to be the most common in several populations. Mutation analysis of the genes for connexin 26, 30 and 31 (GJB2, GJB6 and GJB3) was performed in 67 patients with profound hearing loss. Of the participants, 9% had two pathogenic mutations in the GJB2 gene. Pedigree information indicates that in these families further offspring have a 25% to a 100% chance of having hearing impairment. Patients with non-syndromic hearing impairment should be offered molecular diagnostics of the GJB2 gene. Genetic counseling is mandatory for mutation carriers in order to advise them on the individual consequences of the gene test results.

Ten-year outcome of newborn hearing screening in Austria

Current health care standards recommend that congenital hearing loss be confirmed before age three months and intervened for before age six months. This study evaluated to what extent the Austrian universal neonatal hearing screening (UNHS) program achieves this goal. The Austrian UNHS program is a hospital-based, two-stage screen based on transient oto-acoustic emissions, as promoted in 1995 in a position paper of the Austrian ENT Society. Retrospective chart review and data analysis. All Austrian institutions engaged in the diagnosis and treatment of childhood hearing loss were requested to provide their data on children with permanent congenital sensorineural hearing impairment registered since 1990. Children who had undergone hearing screening, were compared to those who had not. Main outcome measures were age at confirmation of and age at intervention for the hearing loss. In each group, the percentage of children, whose hearing loss was confirmed by age three months, and intervened for by age six months, was determined. Data from 321 hearing-impaired children were useable. Of these children, 167 were screened and 154 were not. At age three months, a hearing loss was diagnosed in 35% of screened children, but in only 2% of unscreened. These percentages rose to 69% and 6%, respectively, at age six months and to 81% and 12%, respectively, at age one year. Intervention mostly started within less than one month after diagnosis. At age six months, 61% of screened children, but only 4% of unscreened children, had undergone intervention. Hearing screening enormously increases the number of early-detected children. However, in quite a few screened children hearing loss is neither confirmed within three months after birth, nor intervened for within six months after birth. Reasons for the delay must be paid attention in order to warrant that UNHS can be as effective as possible.