Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss.

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.

Inner ear salivary gland choristoma extending to the middle ear with congenital profound hearing loss and facial palsy: a case report.

BACKGROUND: Salivary gland choristoma (SGCh) is a rare benign tumor reported in several unusual sites, such as the gastrointestinal tract, the optic nerve, and the internal auditory canal, but never reported in the inner ear. CASE PRESENTATION: An 8-year-old girl with a history of left profound congenital hearing loss presented to us with ipsilateral progressive severe facial nerve palsy (House-Brackmann Grade VI). The left tympanic membrane was swollen with a pulsatile tumor. Radiological investigations revealed a multilocular tumor in the inner ear extending into the middle ear and internal auditory canal (IAC). We performed a partial resection of the tumor by transmastoid approach to preserve the anatomical structure of the facial nerve. The tumor was pathologically diagnosed as SGCh. Two years after surgery, her facial function recovered to House-Brackmann Grade II and the residual tumor did not show regrowth on MRI. CONCLUSIONS: Although the natural course of this rare tumor is unknown, a partial resection is an acceptable treatment procedure when functional recovery of the facial nerve is anticipated.

Correlation of pathogenic effects of laryngopharyngeal reflux and bacterial infection in COME of children.

BACKGROUND: Bacteria infection and laryngopharyngeal reflux (LPR) were believed the important pathogenesis of chronic otitis media with effusion (COME). But no study researched the relationship between them on COME. AIMS: To confirm bacterial could arrive middle ear through LPR and produced acid metabolites to activate the pepsinogen of LPR causing COME. MATERIAL AND METHODS: Children (65) diagnosed COME with 122 middle ear effusions were included in COME group. Children (22) with congenital/acquired profound deafness with 22 middle ear lavage were included in CI group. Pepsin A concentration in the effusion and lavage fluid were measured. The DNA of the bacteria, IL-8 and TNF-α in the effusion were detected. RESULTS: The average concentration of pepsin A in the effusions and lavage were 176.65 ± 242.09 and 19 ng/ml. Bacterial infection rates were 75.76% and 24.24% in the pepsin A(+) and pepsin A(-) patients. In the bacterial (+), the patients of pepsin A(+) was 4.33 times higher than those of pepsin A(-). TNF-α in pepsin A(+) was higher than that in pepsin A(-). TNF-α and IL-8 were higher in bacteria(+) than those of bacteria(-). CONCLUSIONS: Bacterial infection and LPR might act in synergy in the pathogenesis of COME. SIGNIFICANCE: First time to propose LPR and bacterial infection might work synergistically to cause COME.

Phenotype and treatment of elderly onset compared with younger onset rheumatoid arthritis patients in international daily practice.

OBJECTIVE: To identify possible differences in baseline characteristics, initial treatment and treatment response between RA patient subgroups based on age at disease onset. METHODS: Daily practice data from the worldwide METEOR registry were used. Patients (7912) were stratified into three age-groups (age at disease diagnosis <45 years, 45-65 years, >65 years). Initial treatment was compared between the different age-groups. With Cox regression analyses the effect of age-group on time-to-switch from first to second treatment was investigated, and with linear mixed models differences in response to treatment (DAS and HAQ) between the age-groups were assessed, after correction for potential confounders. RESULTS: The >65 years age-group included more men, and more seronegative RA with somewhat higher inflammatory markers. Initial treatment choices differed only slightly between the age-groups, and the time-to-switch from initial treatment to the next was similar. DAS and HAQ improvement were dependent on the age-group, reflected by a significant interaction between age-group and outcome. The stratified analysis showed a difference of -0.02 and -0.05 DAS points and, -0.01 and 0.02 HAQ points per month in the <45 and 45-65 years age-groups as compared with the >65 year age group, a difference that did not seem clinically relevant. CONCLUSION: In this international study on worldwide clinical practice, patients with RA onset >65 years include more men and seronegative arthritis, and were initially treated slightly differently than younger patients. We observed no clinically relevant differences in timing of a next treatment step, or response to treatment measured by DAS and HAQ.

Spliceosomopathies and neurocristopathies: Two sides of the same coin?

Mutations in core components of the spliceosome are responsible for a group of syndromes collectively known as spliceosomopathies. Patients exhibit microcephaly, micrognathia, malar hypoplasia, external ear anomalies, eye anomalies, psychomotor delay, intellectual disability, limb, and heart defects. Craniofacial malformations in these patients are predominantly found in neural crest cells-derived structures of the face and head. Mutations in eight genes SNRPB, RNU4ATAC, SF3B4, PUF60, EFTUD2, TXNL4, EIF4A3, and CWC27 are associated with craniofacial spliceosomopathies. In this review, we provide a brief description of the normal development of the head and the face and an overview of mutations identified in genes associated with craniofacial spliceosomopathies. We also describe a model to explain how and when these mutations are most likely to impact neural crest cells. We speculate that mutations in a subset of core splicing factors lead to disrupted splicing in neural crest cells because these cells have increased sensitivity to inefficient splicing. Hence, disruption in splicing likely activates a cellular stress response that includes increased skipping of regulatory exons in genes such as MDM2 and MDM4, key regulators of P53. This would result in P53-associated death of neural crest cells and consequently craniofacial malformations associated with spliceosomopathies.

Hereditary Hearing Impairment with Cutaneous Abnormalities.

Syndromic hereditary hearing impairment (HHI) is a clinically and etiologically diverse condition that has a profound influence on affected individuals and their families. As cutaneous findings are more apparent than hearing-related symptoms to clinicians and, more importantly, to caregivers of affected infants and young individuals, establishing a correlation map of skin manifestations and their underlying genetic causes is key to early identification and diagnosis of syndromic HHI. In this article, we performed a comprehensive PubMed database search on syndromic HHI with cutaneous abnormalities, and reviewed a total of 260 relevant publications. Our in-depth analyses revealed that the cutaneous manifestations associated with HHI could be classified into three categories: pigment, hyperkeratosis/nail, and connective tissue disorders, with each category involving distinct molecular pathogenesis mechanisms. This outline could help clinicians and researchers build a clear atlas regarding the phenotypic features and pathogenetic mechanisms of syndromic HHI with cutaneous abnormalities, and facilitate clinical and molecular diagnoses of these conditions.

Auditory comprehension outcomes in children who receive a cochlear implant before 12 months of age.

OBJECTIVE: The U.S. Food and Drug Administration guidelines for cochlear implantation (CI) include age greater than 12 months. Studies have suggested that implantation in children younger than 12 months with congenital deafness may be associated with better spoken language outcomes. Compare auditory comprehension (AC) outcomes for children with congenital deafness who received CI less than 12 months of age to those implanted at 12 to 24 months of age. METHODS: Retrospective review of prospectively collected data in consecutively implanted patients under 2 years of age who received CI and had post-CI Preschool Language Scale (PLS)-AC scores. Receptive language was assessed with the AC subtest of the PLS. Patients without pre-CI PLS-AC scores were excluded. The association between age at implantation and post-CI PLS-AC scores up to 2 years after CI surgery was modeled using a linear mixed-effects model. Time from CI surgery, number of implants, risk factors for language delay, pre-CI PLS-AC score, and sex were included in the model. Patients implanted less than 12 months of age were compared to those implanted between 12 and 24 months. RESULTS: Twenty-nine patients who had CI surgery by 12 months and 82 who had CI surgery between 12 and 24 months were included in the analysis. Younger age at implantation and better pre-CI PLS-AC scores were significantly associated with better post-CI PLS-AC scores. CONCLUSION: Cochlear implantation in children with congenital deafness less than 12 months of age was associated with better PLS-AC than in children implanted over 12 months of age up to 2 years after implantation. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:776-781, 2020.

Outer retinal tubulation and inner retinal pseudocysts in a patient with maternally inherited diabetes and deafness evaluated with optical coherence tomography angiogram.

A 47-year-old lady (index case) with diabetes and deafness showed multiple oval circumferential areas of perifoveal atrophy in both eyes. Autofluorescence revealed areas of hypoautofluorescence. Optical coherence tomography (OCT) showed depression of inner retinal surface, inner retinal hyporeflective spaces (pseudocysts), disorganization/thinning of outer retina, outer retinal tubulation, loss of external limiting membrane, ellipsoid and interdigitation zone, and thinning of the retinal pigment epithelium and choriocapillaris. The patient was evaluated using OCT angiogram. Retinal lesions of her mother (68-year-old) were very obvious on autofluorescence imaging. The result of A3243G mutation in MTTL1 gene was positive in the index case confirming the diagnosis of maternally inherited diabetes and deafness (MIDD).

Cochlear Implantation Outcomes in Children with Agenesis of the Corpus Callosum: A Retrospective Study and A Review of the Literature.

OBJECTIVES: The aim of the present study was to analyze the outcomes of cochlear implantation (CI) in patients with agenesis of the corpus callosum (CCA). A literature review and a retrospective analysis of our cochlear implant database were performed. MATERIALS AND METHODS: To the best of our knowledge, in the English literature, there was only one case reported with CCA who had undergone CI surgery. This case had Donnai-Barrow syndrome. In the Cukurova University School of Medicine Department of Otorhinolaryngology database, 5 of the 1317 patients who underwent CI surgery who had CCA were selected. The patients' demographic characteristics, operative findings, surgical outcomes, and additional disabilities were investigated. The patients' preoperative and postoperative Listening Progress Profile (LiP) and Meaningful Auditory Integration Scale (MAIS) tests were done to analyze the auditory performances. RESULTS: The participants of the study were 5 (0.38%) individuals (2 male and 3 female patients; ages 5.5, 7.5, 8, 9, and 12 years). Two of the patients had total agenesis, and the other three had partial agenesis of the CCA. In the histories of the patients, one patient had parental consanguinity, and one had febrile convulsion. No patient had an additional disability. None had experienced device failure. No patients were non-users or limited users of cochlear implants. Postoperative LiP and MAIS test scores were improved for all patients nearly as the patients without any deformity. They showed normal auditory performance in the analysis in their postoperative 48 months of follow-up. CONCLUSION: Patients who had CCA are good candidates for CI surgery.

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases.

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel's aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations.

Detecting novel mutations and combined Klinefelter syndrome in Usher syndrome cases.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS. OBJECTIVES: This study examined the causative genes in three Chinese probands with congenital hearing loss. MATERIAL AND METHODS: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy. RESULTS: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis. CONCLUSIONS: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.

Pathogenic Variants in GPC4 Cause Keipert Syndrome.

Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type. Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features. Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities. Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome. Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.

Speech development in young children with Mondini dysplasia who had undergone cochlear implantation.

OBJECTIVE: The purpose of this study was to investigate the development of speech skills in young children with Mondini dysplasia and age-matched deaf children with radiologically normal inner ears over a period of 5 years after cochlear implantation (CI). METHODS: In total, 700 congenitally severely to profoundly deaf children (281 girls and 419 boys) participated in this study. All of the participants had undergone unilateral CI surgery before 36 months of age. The participants were categorized into two groups based on the absence or presence of Mondini dysplasia in the implanted ear, as assessed via high-resolution, thin-slice computerized tomography or magnetic resonance imaging: group A comprised 592 children with radiologically normal inner ears and group B comprised 108 children with Mondini dysplasia. The Meaningful Use of Speech Scale (MUSS) and Speech Intelligibility Rating (SIR) were used to evaluate the speech performance of all young children at various time points: pre-surgery and at 1, 3, 6, 12, 24, 36, 48, and 60 months after switch-on programming. RESULTS: The mean scores of SIR and MUSS in children from both group A and group B showed significant improvements over time. No significant differences were found in the mean scores of SIR between the two groups at any time interval during the 5-year follow-up. The mean score of MUSS was significantly different between group A and group B at 12, 24, and 36 months after implantation, whereas no obvious differences were noted pre-surgery, and at 1, 3, 6, 48, and 60 months post-operation. CONCLUSIONS: Young children with Mondini dysplasia develop their speech skills at a fast rate and achieve similar speech acquisition compared to age-matched children with radiologically normal inner ears 5 years post-operation. Therefore, CI is an effective intervention method for young children with Mondini dysplasia.

[Screening for hotspot mutations associated with genetic hearing impairment in pregnant women and subsequent prenatal diagnosis in high risk pregnancies].

Objective: To screen for hotspot gene mutations associated with genetic deafness in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis in high-risk families. Methods: Between November 2012 and October 2017, 26 117 pregnant women were screened by molecular hybridization microarray for 9 hot-spot mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191 del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G, IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype analysis was carried out in husbands of women carrying mutations, and prenatal diagnosis was carried out in the fetuses with high risk of deafness. Results: Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations, 7 with hearing impairment were affected by homozygous or compound heterozygous mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4 heterozygous mutations, and 21 carried heterozygous mutations in two genes simultaneously. In 394 families, the husbands accepted gene sequence testing, and 27 in which were determined as carriers of mutations in identical genes as their wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were diagnosed as hereditary deafness. In 9 families who did not receive prenatal diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery. Conclusion: In order to prevent birth defects with congenital hearing problems, it is effective to provide screening for hotspot mutations in pregnant women and to perform prenatal diagnosis on high risk pregnancies.

The Effects of Gusher-Related Intracochlear Pressure Changes on Hearing Preservation in Cochlear Implantation: A Comparative Series.

AIM: To investigate and compare residual hearing preservation between patients based on the presence of intraoperative gusher. METHODOLOGY: We retrospectively compared 2 cohorts of cochlear implant recipients significantly distinguished by whether or not they experienced gusher intraoperatively. Patients underwent cochlear implantation using 24-mm lateral wall electrode arrays as well pharmacologic steroid protection. All patients were assessed by a hearing implant MDT. Hearing preservation rates and speech perception outcomes were assessed at 1, 6, 12, 24, 36, 48, and 60 months. RESULTS: The patients with no gusher demonstrated complete hearing preservation. The patients with gusher demonstrated significant postoperative reduction of hearing thresholds, which declined at a significantly higher pace during follow-up. All patients demonstrated significantly better speech performance after cochlear implantation. CONCLUSION: The present study suggests that intraoperative gusher is associated with a significant drop in residual hearing, both immediately and over time, which may be related to the large change in intracochlear pressure intraoperatively.

Rare case of bilateral aural atresia and cochlear dysplasia: when cochlear implantation is not the answer.

OBJECTIVE AND IMPORTANCE: Reports of patients with concurrent middle and inner ear anomalies are rare. These patients present a surgical challenge for cochlear implantation. The surgical risk must be weighed against the predicted benefit of the patient's hearing outcome and subsequent development of speech and language as well as their quality of life. CLINICAL PRESENTATION: Thirteen-year-old boy presented to the Otology clinic for auditory rehabilitation options. He has mild developmental delay, is non-verbal and communicates via American Sign Language. He was born with bilateral aural atresia and never wore amplification. On exam he has grade 1 microtia and complete ear canal atresia bilaterally. His behavioural hearing test shows profound sensorineural hearing loss of both ears. The computed tomography scan shows bilateral underdeveloped and completely opacified mastoid and middle ear, complete bony atresia of the ear canals, and an under-partitioned cochlea with poorly defined modiolus, among other abnormalities. The patient and his family were counselled on the available options as well as the need for any further studies. INTERVENTION: Counselling of patient and family. CONCLUSION: While there have been reports in the literature of performing cochlear implantations in patients with a concurrent atresia and cochlear dysplasia, these were patients whose degree of inner ear anomalies was relatively minor and their prognosis of a good audiological outcome was favourable. The presented case is that of a patient for whom the surgical approach to the cochlea alone would be difficult. More importantly, his quality of life would not significantly improve in light of the predicted limited hearing and language development outcomes, given the severity of his inner ear abnormalities, limited communication abilities, prolonged period of deafness and developmental delays.

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent de novo mutation in the POLD1 gene.

Segmental progeroid syndromes with lipodystrophy are extremely rare, heterogeneous, and complex multi-system disorders that are characterized by phenotypic features of premature aging affecting various tissues and organs. In this study, we present a "sporadic/isolated" Japanese woman who was ultimately diagnosed with mandibular hypoplasia, deafness, progeroid features, and progressive lipodystrophy (MDPL) syndrome (MIM #615381) using whole exome sequencing analysis. She had been suspected as having atypical Werner syndrome and/or progeroid syndrome based on observations spanning a 30-year period; however, repeated genetic testing by Sanger sequencing did not identify any causative mutation related to various subtypes of congenital partial lipodystrophy (CPLD) and/or mandibular dysplasia with lipodystrophy (MAD). Recently, MDPL syndrome has been described as a new entity showing progressive lipodystrophy. Furthermore, polymerase delta 1 (POLD1) gene mutations on chromosome 19 have been identified in patients with MDPL syndrome. To date, 21 cases with POLD1-related MDPL syndrome have been reported worldwide, albeit almost entirely of European origin. Here, we identified a de novo mutation in exon 15 (p.Ser605del) of the POLD1 gene in a Japanese case by whole exome sequencing. To the best of our knowledge, this is the first identified case of MDPL syndrome in Japan. Our results provide further evidence that mutations in POLD1 are responsible for MDPL syndrome and serve as a common genetic determinant across different ethnicities.

Initial Results of a Safety and Feasibility Study of Auditory Brainstem Implantation in Congenitally Deaf Children.

OBJECTIVE: To determine the safety and feasibility of the auditory brainstem implant (ABI) in congenitally deaf children with cochlear aplasia and/or cochlear nerve deficiency. STUDY DESIGN: Phase I feasibility clinical trial of surgery in 10 children, ages 2 to 5 years, over a 3-year period. SETTING: Tertiary children's hospital and university-based pediatric speech/language/hearing center. INTERVENTION(S): ABI implantation and postsurgical programming. MAIN OUTCOME MEASURE(S): The primary outcome measure is the number and type of adverse events during ABI surgery and postsurgical follow-up, including behavioral mapping of the device. The secondary outcome measure is access to and early integration of sound. RESULTS: To date, nine children are enrolled. Five children have successfully undergone ABI surgery and postoperative behavioral programming. Three children were screen failures, and one child is currently undergoing candidacy evaluation. Expected adverse events have been documented in three of the five children who received the ABI. One child experienced a cerebral spinal fluid leak, which resolved with lumbar drainage. One child demonstrated vestibular side effects during device programming, which resolved by deactivating one electrode. One child experienced postoperative vomiting resulting in an abdominal radiograph. Four children have completed their 1-year follow-up and have speech detection thresholds of 30 to 35 dB HL. Scores on the IT-MAIS/MAIS range from 8 to 31 (out of a total of 40), and the children are demonstrating some ability to discriminate between closed-sets words that differ by number of syllables (pattern perception). CONCLUSION: ABI surgery and device activation seem to be safe and feasible in this preliminary cohort.

RETINAL VEIN OCCLUSION IN A PATIENT WITH MATERNALLY INHERITED DIABETES AND DEAFNESS.

PURPOSE: To report a case of maternally inherited diabetes and deafness complicated by branch retinal vein occlusion and cystoid macular edema. METHODS: Retrospective case report. Multimodal imaging including spectral domain optical coherence tomography, en face optical coherence tomography, and fundus autofluorescence was preformed, and the findings are presented. FINDINGS: A 58-year-old female with a history of diabetes mellitus, hearing loss, and a previous diagnosis of age-related macular degeneration presented with decreased vision in the right eye. Clinical examination and multimodal imaging demonstrated a right inferior branch retinal vein occlusion complicated by cystoid macular edema and bilateral maculopathy suspicious for maternally inherited diabetes and deafness. Genetic testing confirmed an A3243G mitochondrial mutation. CONCLUSION: Multimodal retinal imaging is a key to guide diagnosis of rare genetic diseases such as maternally inherited diabetes and deafness. We report the unusual presentation of maternally inherited diabetes and deafness complicated by branch retinal vein occlusion and cystoid macular edema.

Saving Deaf Children? Screening for Hearing loss as a Public-interest Case.

New-born screening programs for congenital disorders and chronic disease are expanding worldwide and children "at risk" are identified by nationwide tracking systems at the earliest possible stage. These practices are never neutral and raise important social and ethical questions. An emergent concern is that a reflexive professionalism should interrogate the ever earlier interference in children's lives. The Flemish community of Belgium was among the first to generalize the screening for hearing loss in young children and is an interesting case to study the public justification of early interventions for families with deaf children. This article uses a critical lens to study the archive of the government child healthcare organization in Flanders in order to uncover underlying constructions of childhood, deafness, and preventive health. We focus on two interrelated themes. The first is the notion of exclusion of the human factor through the mediation of technology. The second is the idea of deafness as endangering a healthy development, an impairment that can nevertheless be treated if detected early enough. It is argued that, since deafness cannot be viewed as a life-threatening condition, the public interest which is implicitly defended is not the rescue of deaf children rather the exclusion of otherness.