Sensorineural deafness in purebred white Devon Rex cats.

BACKGROUND: Data regarding congenital sensorineural deafness (CSD) in client-owned, white Devon Rex cats is limited because most of the information on this disease comes from experiments on mixed-breed cats. OBJECTIVES: Provide data on the occurrence of CSD in a population of client-owned purebred white Devon Rex cats. ANIMALS: Forty client-owned, purebred, white Devon Rex cats examined at 2 different facilities. Median age of the examined cats was 19 weeks. METHODS: Hearing status was defined by use of brainstem auditory evoked responses. RESULTS: The occurrence of sensorineural deafness in the studied population of Devon Rex cats was estimated at 10%. Unilateral and bilateral deafness occurred equally often, with 2 individuals having each (ie, 5.0%). No association between the occurrence of CSD and sex could be found, χ2 (1, n = 40) = 0.001 (P > .99). No association between blue irises and deafness was noted in the studied population, χ2 (1, n = 40) < 0.01 (P > .99). CONCLUSIONS: The occurrence of CSD in a population of client-owned, white Devon Rex cats was found to be lower compared with data obtained in previously conducted studies of deafness in purebred cats. In the studied population of Devon Rex cats, no association between blue irises and CSD was found.

Vaccine value profile for cytomegalovirus.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Imaging in children with hearing loss. / Bildgebende Diagnostik bei Schwerhörigkeit im Kindesalter.

BACKGROUND: Since the introduction of hearing screening in Germany in 2009, pediatric hearing disorders are detected at an early stage. Early therapy is essential for language development. Imaging plays a central role in diagnosis and therapy planning. METHOD: Imaging findings of the most relevant causes of pediatric hearing disorders are presented. Specific attention is given to the method used in each case - CT or MRI. RESULTS AND CONCLUSIONS: While CT is the method of choice for conductive hearing loss, a combination of CT and MRI with high-resolution T2-3D sequences has been established as the best diagnostic method for sensorineural hearing loss. The most common causes of conductive hearing loss in childhood are chronic inflammation and cholesteatoma. Congenital malformations of the outer or middle ear are less frequent. In the case of sensorineural hearing loss, the cause is located in the inner ear and/or the cochlear nerve or the cerebrum. In these cases, congenital malformations are the most common cause. KEY POINTS: · CT and MRI are necessary to identify morphological causes of hearing disorders and to clarify the possibility of hearing-improving ear surgery or cochlear implantation.. · Contraindications for surgical procedures must be excluded.. · Anatomical variants that may be risk factors for surgery must be described.. CITATION FORMAT: · Sorge I, Hirsch F, Fuchs M et al. Imaging diagnostics for childhood hearing loss. Fortschr Röntgenstr 2023; 195: 896 - 904.

Postnatal genetic umbilical cord analysis for earliest possible detection of inherited hearing impairment.

INTRODUCTION: The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient. METHODS: We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible. RESULTS: 49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery. CONCLUSION: This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.

Long-term outcome of vestibular function and hearing in children with congenital cytomegalovirus infection: a prospective cohort study.

PURPOSE: Congenital cytomegalovirus infection (cCMV) is the most frequent nonhereditary cause for sensorineural hearing loss (SNHL) in children. Data on vestibular function in children with cCMV are, however, scarce, although some evidence for cCMV-associated vestibular dysfunction exists. In this prospective cohort study, we evaluated long-term vestibular function and hearing outcomes in a cohort of children with cCMV. METHODS: Participants were 6-7-year-old children with cCMV from a large population-based screening study. Controls were age and gender matched healthy children, who were CMV-negative at birth. Hearing was examined with pure tone audiometry. Definition of hearing loss was pure-tone average > 20 dB. Vestibular function was assessed using the video head impulse test that provides a measure of semicircular canal function. Definition of vestibular dysfunction was lateral semicircular canal gain < 0.75. RESULTS: Vestibular dysfunction occurred in 7/36 (19.4%) of children with cCMV and in 1/31 (3.2%) of controls (p = 0.060). SNHL was recorded in 4/38 (10.5%) of children with cCMV and in 0/33 of controls (p = 0.118). Hearing loss was unilateral in all cases. In cCMV group, the two children with bilateral vestibular dysfunction also had SNHL, whereas those with unilateral vestibular dysfunction (n = 5) had normal hearing. CONCLUSIONS: In this cohort of children with cCMV identified using newborn screening, vestibular dysfunction was more common than SNHL at 6 years of age. Vestibular dysfunction occurred both in children with and without SNHL. Based on these data, inclusion of vestibular tests in follow-up protocol of cCMV should be considered.

Targeted screening for congenital cytomegalovirus infection: clinical, audiological and neuroimaging findings.

OBJECTIVE: To evaluate clinical, audiological and neuroimaging findings in a cohort of infants diagnosed with congenital cytomegalovirus (cCMV) infection after failure at newborn hearing screening. METHODS: A prospective observational study in the Netherlands, using the existing newborn hearing screening infrastructure for well babies. Between July 2012 and November 2016, cytomegalovirus (CMV) PCR testing of neonatally obtained dried blood spots (DBS) was offered to all infants who failed newborn hearing screening. Clinical, neuroimaging and audiological data were collected. RESULTS: DBS of 1374 infants were successfully tested and 59 were positive for CMV (4.3%). Data of 54 infants were retrieved. Three were small for gestational age and six had microcephaly. Forty-eight (89%) had sensorineural hearing loss (SNHL), of whom half had unilateral SNHL. In both unilaterally and bilaterally affected children, the majority of the impaired ears had severe or profound hearing loss. Neuroimaging abnormalities were found in 40 of 48 (83%) children who had evaluable cranial ultrasound and/or cerebral MRI. The abnormalities were mild in 34, moderate in 3 and severe in 3 infants. The degree of SNHL and the severity of neuroimaging abnormalities were found to be correlated (p=0.002). CONCLUSIONS: The yield of targeted cCMV screening following newborn hearing screening failure was eight times higher than the estimated national birth prevalence of cCMV. The majority of this cohort of infants with clinically unsuspected cCMV disease had confirmed SNHL, neuroimaging abnormalities and lower than average birth weights and head circumferences. Newborns who fail newborn hearing screening should be tested for CMV to ensure appropriate clinical, neurodevelopmental and audiological follow-up.

Late-onset and congenital hearing loss detected using AABR due to congenital cytomegalovirus infection that improved with valganciclovir.

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss and an important cause of neurodevelopmental disabilities. Auto auditory brainstem response (AABR) is a simple hearing test and used for the purpose of neonatal hearing screening, but can use it for early detection hard of hearing within the study age of the model. We experienced two case of asymptomatic CMV infection in which congenital and late-onset hearing loss were diagnosed early with AABR, and hearing loss improved with valganciclovir.

De-novo and genome-wide meta-analyses identify a risk haplotype for congenital sensorineural deafness in Dalmatian dogs.

Congenital sensorineural deafness (CSD) has been reported to affect up to 30% of Dalmatian dogs world-wide and while unilaterally deaf dogs can live a close to normal life, dogs suffering bilateral deafness are frequently euthanized. Extreme-white coat patterning as encoded by the gene Melanocyte Inducing Transcription Factor (MITF) has long been postulated as the major risk factor for CSD in the Dalmatian breed. While attempts to identify causative risk variants associated with CSD have been numerous, no genome-wide association study has positively identified MITF as a risk locus for either bilateral or unilateral deafness in the Dalmatian breed to date. In this study, we identified an association with CSD on CFA20 in the vicinity of MITF within Australian Dalmatian dogs. Although not genome-wide significant, the association signal was validated by reanalysing publicly available data and merging the wider data resource with the local data to improve statistical power. The merged data, representing three major global populations of Dalmatian dogs, enabled us to identify a single, well-defined genome-wide significant risk haplotype for CSD. The haplotype was formed by three genome-wide significant associated markers (BICF2G630233852T>C, BICF2G630233861T>C, BICF2G630233888G>A) on CFA20 with 62% of bilaterally deaf dogs homozygous for the risk haplotype (CCA), while 30% of bilaterally deaf and 45% of hearing dogs carried one copy of the risk haplotype. Animals homozygous or heterozygous for the low-risk haplotype were less likely to be unilaterally deaf. While the association between the risk haplotype and deafness is incomplete, animals homozygous for the risk haplotype were 10-times more likely to be bilaterally deaf. Although the underlying causative variants are yet to be discovered, results from this study can now assist with reducing deafness in Dalmatian dogs.

Congenital cytomegalovirus infection diagnostics and management.

PURPOSE OF THE REVIEW: Congenital cytomegalovirus infection (cCMV) is the most frequent congenital infection and a leading nongenetic cause of sensorineural hearing loss (SNHL) and brain disease. The purpose of this review is to highlight recent developments in the diagnosis and management of children with cCMV. RECENT FINDINGS: Progress is being made in the efforts to identify more infants with cCMV, especially those with asymptomatic infection. Largely due to efforts by various advocacy/parent groups, a number of states in the United States and many hospital systems have implemented hearing targeted CMV screening and mandated education of pregnant women about CMV. SUMMARY: cCMV is an important cause of SNHL and neurologic morbidity worldwide. Early identification of infected children is critical to improve outcomes by providing timely interventions and guidance for long-term follow up. The fact that most infants with cCMV have no abnormal clinical findings, and the need to obtain samples for diagnosis within the first 2-3 weeks of life, makes it challenging to identify a majority of infants with cCMV without universal newborn CMV screening.

Universal newborn hearing screening with automated auditory brainstem response (AABR) in Hungary: 5-year experience in diagnostics and influence on the early intervention.

PURPOSE: In 2015 a new regulation and guidelines for the universal newborn hearing screening by AABR measurement have been implemented in Hungary. The aim of our study was to analyse (1) the past 5 years of data from our diagnostic centre about the incidence and types of congenital hearing losses, and (2) the first experiences with the National Newborn Hearing Screening Registry, started in 2019, and (3) the influence of the screening on the pediatric cochlear implant program. METHODS: 1269 children referred to our diagnostic centre between 2017 and 2021 were investigated. A third AABR measurement and full audiological evaluation were performed. Furthermore, one-year period data of the screening registry, and the number of implanted children at or under the age of 3 were analysed using the national databases. RESULTS: Altogether 276 newborns (22% of the referred cases after the two-stage screening) had hearing loss, 134 (49%) out of them was conductive origin, almost twice frequent in male as in female. Permanent sensorineural hearing impairment was found in 142 (51%), 58 (40%) of them had bilateral, severe to profound hearing loss, occurring more frequently in male as in female. The national digital registration of the screening data within 12 months concerned 68%. The number of early cochlear implantation in one year increased from 1 to 23 children in the past 15 years. CONCLUSION: A third AABR after the two-stage screening increased the efficiency and filtered the 78% false-positive cases. The audiological diagnostics verified and typed the hearing losses ensuring the early intervention.

Three Years of Vestibular Infant Screening in Infants With Sensorineural Hearing Loss.

OBJECTIVES: Although vestibular deficits are more prevalent in hearing-impaired children and can affect their development on many levels, a pediatric vestibular assessment is still uncommon in clinical practice. Since early detection may allow for timely intervention, this pioneer project has implemented a basic vestibular screening test for each six-month-old hearing-impaired infant in Flanders, Belgium. This study aims to report the vestibular screening results over a period of three years and to define the most important risk factors for abnormal vestibular screening results. METHODS: Cervical Vestibular Evoked Myogenic Potentials with bone-conduction were used as a vestibular screening tool in all reference centers affiliated to the Universal Newborn Hearing Screening Program in Flanders. From June 2018 until June 2021, 254 infants (mean age: 7.4 months, standard deviation: 2.4 months) with sensorineural hearing loss were included. RESULTS: Overall, abnormal vestibular screening results were found in 13.8% (35 of 254) of the infants. The most important group at risk for abnormal vestibular screening results were infants with unilateral or bilateral severe to profound sensorineural hearing loss (20.8%, 32 of 154) (P < .001, odds ratio = 9.16). Moreover, abnormal vestibular screening results were more prevalent in infants with hearing loss caused by meningitis (66.7%, 2 of 3), syndromes (28.6%, 8 of 28), congenital cytomegalovirus infection (20.0%, 8 of 40), and cochleovestibular anomalies (19.2%, 5 of 26). CONCLUSIONS: The vestibular screening results in infants with sensorineural hearing loss indicate the highest risk for vestibular deficits in severe to profound hearing loss, and certain underlying etiologies of hearing loss, such as meningitis, syndromes, congenital cytomegalovirus, and cochleovestibular anomalies.

Cytomegalovirus variation among newborns treated with valganciclovir.

Congenital cytomegalovirus (cCMV) infection is the leading non-genetic cause of long-term neurological and sensory sequelae, the most common being sensorineural hearing loss (SNHL). Standard therapy for infants with symptomatic cCMV is valganciclovir for six months. However, little is known about the effects of antiviral therapy on CMV diversity while patients are on treatment. In this study, CMV variation was analyzed from urine specimens isolated from two patients with cCMV shortly after birth and at seven months. One was treated with valganciclovir for six weeks and the other for six months. In order to track these variants a novel bioinformatic approach was employed to analyze changes in low frequency variants over time. In the infant receiving antivirals for only six weeks, there was a fourfold increase in variation in UL97 from the seven month specimen. Furthermore, an eightfold increase in variation was seen in UL83 (pp65) with seven potential escape mutations occurring, and a twofold increase in UL73 (gN). In contrast variation did not increase or was reduced in these coding regions in the infant receiving valganciclovir for six months. However, there were increases in other CMV regions in samples isolated from both patients indicating further longitudinal studies are warranted to better understand the interplay between CMV diversity, antiviral therapy and patient outcome.

Hearing outcome in congenitally CMV infected children in Finland - Results from follow-up after three years age.

OBJECTIVES: Cytomegalovirus (CMV) is the most common congenital infection affecting about 0.6% of all newborns in developed countries. Vertical transmission to fetus can take place either after maternal primary or non-primary CMV infection during pregnancy. It is the most common infectious agent for sensorineural hearing loss (SNHL) in young children. The hearing loss after congenital CMV (cCMV) may be present at birth, or may develop after months or even years. In this study, we evaluated hearing outcome at 3-4 years of age in children (n 32) with cCMV identified in universal saliva CMV-PCR-based screening. METHODS: Study population consisted of mainly asymptomatic children (median age 3.1 years) with cCMV identified in newborn CMV screening. The type of maternal CMV infection (primary or non-primary) was determined by analyzing CMV antibodies (IgM, IgG and IgG avidity) from preserved maternal serum samples drawn in the end of first trimester of pregnancy. Hearing was evaluated with pure tone audiometry (PTA), or transient-evoked otoacoustic emission (TEOAE) and sound field audiometry (SF). RESULTS: Unilateral hearing loss occurred in 5/32 (16%) of the children with cCMV. None of the subjects in our cohort had bilateral hearing loss. Hearing loss occurred in 3/15 (20%) of children who were born to mothers with non-primary CMV infection during pregnancy, and in 2/10 (20%) of children whose mother had had a primary CMV infection during the 2-3 trimester. None of the additional 6 children, whose mother had primary infection in the first trimester, had hearing loss by age of 3-4 years. Two children with normal hearing at 1 years age had developed unilateral hearing loss by the age of three. CONCLUSIONS: Unilateral hearing loss was relatively common among the mainly asymptomatic children with cCMV identified in screening. Long-term follow up of children with cCMV is essential to identify the children with late-onset hearing loss.

Comprehensive Analysis of Factors Affecting Cochlear Size: A Systematic Review and Meta-analysis.

OBJECTIVES: To determine the cochlea's average size in humans and evaluate the relationships between certain covariates and cochlear size. METHODS: A systematic search on articles on cochlear size and published in English was conducted using Cochrane, PubMed, Web of Science, and Scopus databases up to September 15, 2020. Data were pooled using random-effects with three models. The effect of demographic, clinical, and measurement-related parameters was specifically analyzed. Meta-regression and subgroup analyses were conducted. The overall effect estimation was made for outcomes. RESULTS: The meta-analysis included 4,708 cochleae from 56 studies. The overall length of the organ of Corti was 32.94 mm (95% confidence interval [CI]: 32.51-33.38). The first and second models revealed that age, gender, country, continent, measurement method (direct, indirect), measured structure ("A" value, cochlear lateral wall), origin (in vivo, in vitro), and type (histology specimens, plastic casts, imaging) of the cochlear material did not affect the cochlear size. However, study populations (general population, patients with a cochlear implant, and patients with congenital sensorineural hearing loss [CSNHL]) were found to affect the outcomes. Compared to the other populations, patients with CSNHL had shorter cochleae. Therefore, we developed a third model and found that the general population and patients with cochlear implants did not differ in cochlear size. CONCLUSION: This meta-analysis investigated the factors that could affect the cochlear size and found that patients with CSNHL had significantly shorter cochleae, whereas other covariates had no significant effect. Laryngoscope, 132:188-197, 2022.

Resolution of auditory neuropathy spectrum disorder after shunt placement in a patient with hydrocephalus: A case report.

PURPOSE: There have been previous case reports suggesting the resolution of both sensorineural hearing loss and retrocochlear involvement through the management of hydrocephalus with shunt placement. This is a case report of a patient with Auditory Neuropathy Spectrum Disorder (ANSD) that resolved after shunt placement in a patient with hydrocephalus. MATERIALS AND METHODS: Chart review of a single patient with a diagnosis of ANSD and hydrocephalus. Type of audiometric testing and results were document. RESULTS: Patient is an infant who was diagnosed with hydrocephalus at birth and ANSD in the right ear at 3 months of age. Patient underwent shunt placement at 9 months old and had behavioral testing 2 months later. Audiometry showed normal behavioral audiometric thresholds with presence of ipsilateral and contralateral reflexes which is suggestive of resolution of ANSD. CONCLUSIONS: This is a single case report of resolution of ANSD after shunt placement in a patient with hydrocephalus. Close monitoring and repeat audiological evaluation is recommended to follow these patients.

Audiological Features in 63 Patients With Cochlear Nerve Deficiency.

OBJECTIVE: We aimed to investigate the clinical features of cochlear nerve deficiency (CND), and in particular, the long-term course of hearing disability and audiogram shapes. STUDY DESIGN: Retrospective observational nonrandomized group study. SETTING: Academic medical center. PATIENTS/INTERVENTIONS: The subjects were 63 children with congenital hearing loss who visited our hospital between 2009 and 2019 and underwent MRI, based on which they were diagnosed with CND. There were 61 cases of unilateral CND and two cases of bilateral CND. MAIN OUTCOME MEASURES: Imaging tests by MRI and CT and audiometric assessments by pure-tone audiometry and distortion product otoacoustic emission were performed. RESULTS: Among the cases of CND diagnosed by assessing the cochlear nerve on MRI, approximately 20% of the bony cochlear nerve canals that could be assessed on CT were normal. Of the 61 cases diagnosed with unilateral CND, 55 cases had cochlear nerve aplasia (90.2%), and six had cochlear nerve hypoplasia (9.8%), with a mean hearing ability of 92.2 and 94.6 dB HL, respectively. Thus, the majority of cases had severe-to-profound hearing loss. The overall audiometric patterns were 78.7% flat, 9.8% cookie-bite, and 9.8% high-frequency. Six of 61 cases (9.8%) had a distortion product otoacoustic emission (DPOAE) response based on the affected side, and none of the cases lost the response during follow-up. CONCLUSIONS: Herein, we report the largest study on CND and performed CND image and audiometric assessments. Accurately in diagnosing CND requires not only CT but also MRI assessment. Hearing loss is often severe to profound; however, various audiometric patterns have been observed. CND includes a small number of cases that respond to DPOAE, indicating that some CND cases are clinically diagnosed with auditory neuropathy spectrum disorder (ANSD). A sustained DPOAE response might help in differentiating CND from other ANSDs. Children with congenital deafness who have passed the newborn hearing screening by DPOAE should be examined by MRI to rule out CND.

Prevalence of Jervell-Lange Nielsen syndrome in children with congenital bilateral sensorineural hearing loss.

OBJECTIVE: Long QT syndrome (LQTS) is an inherited cardiac ion channel disorder (channelopathy) that is characterized by prolonged QT intervals on the electrocardiography (ECG) and possess the risk of sudden cardiac death (SCD). Jervell-Lange Nielsen syndrome (JLNS) is a specific subtype of LQTS that is accompanied by congenital sensorineural hearing loss, inherited autosomal recessively, and higher risk of SCD. In this study, we aimed to investigate JLNS prevalence in deaf children attending special schools for hearing loss, located in our province. METHODS: An ECG screening program was conducted in 6 special schools for children with hearing loss in Istanbul and a total of 440 students between 6 and 18 years old were included. Corrected QT interval (QTc) was calculated using the Bazett formula. Notably, 51 students, detected with any abnormal finding on ECG, were invited to our center for a comprehensive examination. RESULTS: A total of 8 patients were found with a prolonged QT interval. JLNS was diagnosed in 4 (0.9%) patients. In addition, 2 students had already been diagnosed with JLNS at another center earlier. The other 2 students, being siblings, were newly diagnosed with JLNS; and appropriate treatment was initiated. Genetic testing revealed a pathological homozygous mutation in KCNQ1 gene. The younger sibling (Case 1), who possessed a QTc of greater than 500 ms and a history of syncope, which was very suspicious for SCD, was implanted an implantable cardioverter-defibrillator. Propranolol treatment was initiated for both siblings. CONCLUSION: JLNS should be carefully considered and screened, especially in patients with a history of congenital deafness.

Congenital sensorineural deafness in Australian Cattle dogs in the UK: Prevalence and association with phenotype.

The Australian Cattle dog (ACD) is one of many breeds predisposed to congenital sensorineural deafness (CSD). The objective of this study was to estimate CSD prevalence and investigate any association with phenotype in the ACD in the UK. The database of the authors' institution was searched for ACD puppies undergoing brainstem auditory evoked response (BAER) testing for CSD screening (1999-2019). Inclusion criteria were BAER performed at 4-10 weeks of age, testing of complete litters and available phenotypic data. The age, sex, coat and iris colour, presence and location of face and body patches, hearing status and BAER- determined parental hearing status of each puppy were recorded. A multivariable mixed-effects logistic regression model was used to calculate odds ratios and 95% confidence intervals to determine whether any of these variables were significantly associated with CSD, while adjusting for clustering at litter level. Inclusion criteria were met for 524 puppies. Hearing was bilaterally normal in 464 puppies (88.6%). The prevalence of unilateral and bilateral CSD was 9.7% and 1.7%, respectively. On the basis of multivariable analysis, the presence of a pigmented face patch was the only phenotypic variable significantly associated with CSD, and was linked to a reduced risk of the condition. The prevalence was similar to that reported in an Australian population of ACDs. The key findings from this study were that overall CSD prevalence in the ACD population in the UK was 11.4%, and puppies with a face patch were at reduced risk of the condition.

A Missense Mutation in the KLF7 Gene Is a Potential Candidate Variant for Congenital Deafness in Australian Stumpy Tail Cattle Dogs.

Congenital deafness is prevalent among modern dog breeds, including Australian Stumpy Tail Cattle Dogs (ASCD). However, in ASCD, no causative gene has been identified so far. Therefore, we performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. For GWAS, 3 bilateral deaf ASCDs, 43 herding dogs, and one unaffected ASCD were used, resulting in 13 significantly associated loci on 6 chromosomes, i.e., CFA3, 8, 17, 23, 28, and 37. CFA37 harbored a region with the most significant association (-log10(9.54 × 10-21) = 20.02) as well as 7 of the 13 associated loci. For whole genome sequencing, the same three affected ASCDs and one unaffected ASCD were used. The WGS data were compared with 722 canine controls and filtered for protein coding and non-synonymous variants, resulting in four missense variants present only in the affected dogs. Using effect prediction tools, two variants remained with predicted deleterious effects within the Heart development protein with EGF like domains 1 (HEG1) gene (NC_006615.3: g.28028412G>C; XP_022269716.1: p.His531Asp) and Kruppel-like factor 7 (KLF7) gene (NC_006619.3: g.15562684G>A; XP_022270984.1: p.Leu173Phe). Due to its function as a regulator in heart and vessel formation and cardiovascular development, HEG1 was excluded as a candidate gene. On the other hand, KLF7 plays a crucial role in the nervous system, is expressed in the otic placode, and is reported to be involved in inner ear development. 55 additional ASCD samples (28 deaf and 27 normal hearing dogs) were genotyped for the KLF7 variant, and the variant remained significantly associated with deafness in ASCD (p = 0.014). Furthermore, 24 dogs with heterozygous or homozygous mutations were detected, including 18 deaf dogs. The penetrance was calculated to be 0.75, which is in agreement with previous reports. In conclusion, KLF7 is a promising candidate gene causative for ASCD deafness.

Congenital sensorineural deafness in Dogo Argentino dogs: Prevalence and phenotype associations.

BACKGROUND: The Dogo Argentino dog breed is affected by hereditary congenital sensorineural deafness (CSD) associated with white pigmentation, but prevalence data and associations with phenotypes have not been reported. METHODS: In a retrospective study, animals were tested by the brainstem auditory evoked response, and phenotype data of sex, iris color, patch presence/absence and parent hearing status were collected. Chi-square analyses were performed to identify associations between deafness and phenotype traits. RESULTS: BAER results and phenotype data were collected for 811 dogs. Hearing status was 74.23% bilaterally hearing, 20.35% unilaterally deaf and 5.43% bilaterally deaf or an overall prevalence of 25.77%. CSD was not associated with sex, but dogs without a patch had a significantly higher prevalence rate than patched dogs. Blue-eyed dogs had higher prevalence rates than brown-eyed dogs, but because of small sample size the χ2 association was not considered valid. Insufficient numbers of dogs with a unilaterally deaf parent were present to assess the effects of parent hearing status. CONCLUSION: Approximately one fourth of a US Dogo Argentino population was deaf in one or both ears, but dogs with a patch had a lower prevalence. Dogs with a blue eye were more likely to be deaf, but the association significance could not be reliably assessed.