Unilateral and Bilateral Congenital Sensorineural Deafness in Client-Owned Pure-Breed White Cats

Background: Congenital sensorineural deafness has been reported frequently in experimental mixed-breed white cats but there is a paucity of data on occurrence of deafness in client-owned pure-breed white cats.
Objective: To describe hearing status in client-owned pure-breed white cats.
Animals: Eighty-four pure-breed client-owned cats with white coat color of 10 registered breeds presented for routine hearing evaluation before breeding (1995–2008).
Methods: Hearing was assessed by click-evoked brainstem auditory evoked response.
Results: Overall deafness prevalence was 20.2%; 9 cats (10.7%) were bilaterally deaf and 8 cats (9.5%) were unilaterally deaf. There was no association between sex and deafness status ( P = .85). Deafness status was associated with iris color ( P = .04).
Conclusions and Clinical Importance: Congenital sensorineural deafness frequently occurs in pure-breed cats with white coat color. Unilateral sensorineural deafness was as common as bilateral deafness.     

Complex segregation analysis of deafness in Dalmatians

OBJECTIVE: To use pedigree analysis to evaluate the feasibility of a major locus model for deafness in Dalmatians. ANIMALS: 605 purebred Dalmatians from 42 families. PROCEDURE: Hearing loss was evaluated through the brainstem auditory-evoked response. Dogs were classified into mutually exclusive categories: normal hearing, unilaterally deaf, or bilaterally deaf. Information was collected on sex, coat color, presence or absence of a color patch at birth, and eye color. Statistical analyses were performed by use of regressive logistic models designed for complex segregation analysis. Genetic correlations among eye color, deafness, and color patch were estimated. RESULTS: Prevalence of hearing loss was 11% for dogs classified as unilaterally deaf and 5% for dogs that were bilaterally deaf. Complex segregation analysis detected statistical evidence of a single allele with an expected frequency of 0.21 that had an effect on the prevalence of deafness. Results of analyses suggested that this locus cannot completely explain the inheritance and incidence of deafness in Dalmatians. Genetic correlation estimates among deafness, eye color, and color patch revealed strong interrelationships among these characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: To reduce the incidence of hearing loss in Dalmatians, unilaterally deaf, blue-eyed dogs should not be considered as potential parents.     

Prevalence of unilateral and bilateral deafness in border collies and association with phenotype

BACKGROUND: Congenital sensorineural deafness (CSD) occurs in Border Collies, but its prevalence and inheritance are unknown. This study estimated the prevalence of CSD in Border Collies and investigated its association with phenotypic attributes linked to the merle gene, including coat pigmentation and iris color. HYPOTHESIS: Deafness in Border Collies is associated with pigmentation patterns linked to the merle gene. ANIMALS: A total of 2597 Border Collies from the United Kingdom. METHODS: A retrospective study of Border Collies tested, during 1994-2002, by using brainstem auditory evoked responses. Associations between deafness and phenotypic attributes were assessed by using generalized logistic regression. RESULTS: The prevalence of CSD in puppies was estimated as 2.8%. The corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%, respectively. Adjustment for clustering of hearing status by litter reduced the overall prevalence estimate to 1.6%. There was no association between CSD and sex (P = .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue iris pigment, and excess white on the head than normal hearing Border Collies (all P < .001). The odds of deafness were increased by a factor of 14 for Border Collies with deaf dams, relative to the odds for dogs with normal dams (P = .007), after adjustment for phenotypic attributes. CONCLUSIONS AND CLINICAL IMPORTANCE: Associations between CSD and pigmentation patterns linked to the merle gene were demonstrated for Border Collies. Evidence for an inherited component to CSD in Border Collies supports selective breeding from only tested and normal parents to reduce the prevalence of this disease.     

Further contributions to the genetic aspect of congenital sensorineural deafness in Dalmatians

Sensorineural deafness is a common congenital disorder in Dalmatians and is genetically transmitted. Different modes of inheritance have been proposed and the objective of this study was to study these by segregation analyses using maximum likelihood procedures. Data from 33 complete Dalmatian families were collected and data from 56 single Dalmatians added. This resulted in a total of 575 dogs with 357 known phenotypes. All dogs were clinically evaluated and electrophysiologically tested with brainstem auditory evoked responses.The prevalence of deafness was 16.5% (9.4% unilaterally deaf, 7.1% bilaterally deaf). Females were 4.4% more affected than males but this difference was not significant. Within the same litter, different phenotypic expressions of deafness occurred, which suggested different expressions of the disease. In addition, two data sets were analysed: the first included normal, uni- and bilaterally deaf dogs, the second had normal and deaf Dalmatians. We found that a recessive allele at a single biallelic major locus fitted our data best, although an incomplete penetrance of the recessive homozygotes was observed.     

Use of brain stem auditory-evoked response to evaluate deafness in a group of Dalmatian dogs

A group of 18 adult and 28 six-week-old purebred Dalmatian dogs was tested for hearing by brain stem auditory-evoked responses. Each ear was tested independently. Absence of a response was considered evidence of deafness in that ear. Responses from bilaterally hearing adults and pups and unilaterally hearing dogs were compared with each other and with responses from normally hearing, adult, mixed-breed dogs. Of the 18 adults tested, 5 had normal responses from both ears, 6 were deaf in both ears, and 7 had a response from only one side. Of 28 pups tested, 14 had normal responses from both ears, 9 had a response from only one ear, and 5 were bilaterally deaf. Wave peak latencies from all ears that responded were within normal limits, except that the 5th and 6th waves from unilaterally hearing adults had significantly longer latencies. There were no differences between males and females.     

N3 potentials in response to high intensity auditory stimuli in animals with suspected cochleo-saccular deafness

We describe a previously un-reported vertex-negative potential evoked by high intensity click auditory stimuli in some dogs and cats with suspected cochleo-saccular deafness. Brainstem auditory evoked potential tracings from 24 unilaterally or bilaterally deaf animals, 22 dogs and 2 cats, among which 21 belonged to breeds with high prevalence of suspected or histologically confirmed cochleo-saccular deafness, were studied retrospectively. Values for latency, amplitude and threshold of this potential in dogs were 2.15+/-0.23 ms, 0.49+/-0.25 microV, and 91.9+/-4.7 dB NHL, respectively (mean+/-SD). Latency and threshold values in cats were in the mean+/-2 SD range of the dog values. Sensitivity to click stimulus polarity and to click stimulus delivery rate pointed towards a neural potential instead of a receptor potential. The vertex-negative wave observed in these animals shares all characteristics with the N3 potential described in some deaf humans with cochlear deafness, where it is presumed to arise from saccular stimulation. The combined degeneration of cochlea and sacculus usually reported in deaf white dogs and cats suggest that N3 may have a different origin in these species.     

Deafness prevalence and pigmentation and gender associations in dog breeds at risk

Hearing function was tested in dogs from breeds at risk for pigment-associated congenital sensorineural deafness - Dalmatian, English setter (ES), English cocker spaniel (ECS), bull terrier (BT), Australian cattle dog (ACD), whippet, Catahoula leopard dog, and Jack Russell terrier. Deafness prevalence was highest in Dalmatians and lowest in ECS. Phenotype correlation studies were performed in breeds with >100 brainstem auditory evoked responses (BAER) tested subjects. No gender differences were observed. No differences were seen between black- and liver-spotted Dalmatians, among the ES roan colour varieties, among the ECS parti varieties, or among the ACD colour varieties. Blue eyes were positively associated and patches were negatively associated with deafness in the Dalmatian. Blue eyes were also associated with deafness in the ES and ECS. White BT were more likely than coloured BT to be deaf. Having one or more parent's ear deaf was positively associated with deafness in Dalmatians, ES, and ECS.     

Congenital sensorineural deafness in dogs: a molecular genetic approach toward unravelling the responsible genes

Deafness is often diagnosed in different dog breeds and has been identified as a significant problem for breeders, owners and clinicians. The aetiology can be inherited or acquired, and a distinction must be made between sensorineural and conductive forms of deafness. This paper provides a brief overview of the varieties of findings in different dog breeds and in one breed in particular including prevalence, phenotypic and gender associations, histology, modes of inheritance and the number of contributing genes in congenital sensorineural deafness. We have also described molecular genetic approaches to canine hearing loss and discuss how comparative genomics could help reduce the prevalence of deafness in affected breeds leading to new insights into the molecular mechanisms of auditory function in both dogs and humans.     

Congenital deafness in Jack Russell terriers: Prevalence and association with phenotype

Congenital hereditary sensorineural deafness is the most common form of deafness in dogs. The objectives of this study were to determine a reliable measure of the prevalence of deafness in Jack Russell terriers, an affected breed, and associations between deafness and phenotypic characteristics. Brainstem auditory evoked response recordings and phenotypic parameters (coat color, coat texture, sex, eye color, sire and dam hearing status) were recorded for 1009 Jack Russell terriers. The prevalence of unilateral and bilateral deafness was 3.57% and 0.50%, respectively, lower by a factor of three to four than in earlier reports based on smaller and closely related kindreds. Significant association with deafness was identified with white coat color and parental hearing status, but not with sex or coat type. Lack of significant sex or coat type associations and the significant association with white coat color are consistent with previous reports. In conclusion the prevalence of deafness in Jack Russell terriers is lower than initially reported. Deafness was associated with white coat color and parental hearing status. The association with parental hearing status supports this form of deafness being a heritable trait in the breed and the association with white coat color supports an inheritance linked to pigmentation genes.     

A comparison of the brainstem auditory evoked response in healthy ears of unilaterally deaf dogs and bilaterally hearing dogs

Aims

Auditory plasticity in response to unilateral deafness has been reported in various animal species. Subcortical changes occurring in unilaterally deaf young dogs using the brainstem auditory evoked response have not been evaluated yet. The aim of this study was to assess the brainstem auditory evoked response findings in dogs with unilateral hearing loss, and compare them with recordings obtained from healthy dogs.

Methods

Brainstem auditory evoked responses (amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, wave I-V, I-III and III-V interpeak intervals) were studied retrospectively in forty-six privately owned dogs, which were either unilaterally deaf or had bilateral hearing. The data obtained from the hearing ears in unilaterally deaf dogs were compared to values obtained from their healthy littermates.

Results

Statistically significant differences in the amplitude of wave III and the V/I wave amplitude ratio at 75 dB nHL were found between the group of unilaterally deaf puppies and the control group. The recordings of dogs with single-sided deafness were compared, and the results showed no statistically significant differences in the latencies and amplitudes of the waves between left- (AL) and right-sided (AR) deafness.

Conclusions

The recordings of the brainstem auditory evoked response in canines with unilateral inborn deafness in this study varied compared to recordings from healthy dogs. Future studies looking into electrophysiological assessment of hearing in conjunction with imaging modalities to determine subcortical auditory plasticity and auditory lateralization in unilaterally deaf dogs are warranted.

     

Unilateral and Bilateral Brainstem Auditory-Evoked Response Abnormalities in 900 Dalmatian Dogs

In a survey of 900 Dalmatian dogs, brainstem auditory-evoked responses (BAER) and clinical observations were used to determine the incidence and sex distribution of bilateral and unilateral BAER abnormalities and their association with heterochromia iridis (HI). To assess the efficacy of BAER testing in guiding breeding programs, data from 749 dogs (subgroup A), considered to be a sample of the population at large, were compared with data from a subgroup (subgroup B; n = 151) in which selection of breeding stock had been based on BAER testing from the beginning of the 4-year survey. Brainstem auditory-evoked responses were elicited by applying click stimuli unilaterally, while applying a white noise masking sound to the contralateral ear. Under these conditions, BAER were either normal, unilaterally absent, or bilaterally absent. Dogs with bilaterally absent BAER were clinically deaf; dogs with unilaterally absent BAER were not clinically deaf but appeared dependent on their BAER-normal ears for their auditory-cued behavior. Dogs with unilaterally absent BAER often were misidentified as normal by uninformed observers. Among the 900 dogs, 648 (72.0%) were normal, 189 (21.0%) had unilateral absence of BAER, and 63 (7.0%) had bilateral absence of BAER or were clinically deaf and assumed to have bilaterally absent BAER (n = 4). Total incidence in the population sampled was assumed to be higher, because some bilaterally affected dogs that would have been members of subgroup A undoubtedly did not come to our attention. Among females, 24.0% were unilaterally abnormal and 8.2% were bilaterally abnormal whereas, among males, 17.8% were unilaterally abnormal and 5.7% were bilaterally abnormal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post‐anesthesia deafness in dogs and cats following dental and ear cleaning procedures

Objective The present study was performed to document hearing loss in dogs and cats following procedures performed under anesthesia. Most cases of reported hearing loss were subsequent to dental and ear cleaning procedures. Study design Prospective and retrospective case survey. Animals Subjects were dogs and cats with deafness, personally communicated to one author, cases discussed on a veterinary information web site, and cases communicated through a survey of general practice and dental specialist veterinarians. Methods Reported deafness cases were characterized by species (dog, cat), breed, gender, age, and dog breed size. Results Sixty‐two cases of hearing loss following anesthesia were reported between the years 2002 and 2009. Five additional cases were reported by survey respondents. Forty‐three cases occurred following dental procedures. Sixteen cases occurred following ear cleaning. No relationship was observed between deafness and dog or cat breed, gender, anesthetic drug used, or dog size. Geriatric animals appeared more susceptible to post‐anesthetic, post‐procedural hearing loss. Conclusions Deafness may occur in dogs and cats following anesthesia for dental and ear cleaning procedures, but the prevalence is low. The hearing loss appears to be permanent. Clinical relevance Deafness can be a consequence following anesthesia for dental or ear cleaning procedures. Older animals may have greater susceptibility.     

Brainstem auditory-evoked potential assessment of auditory function and congenital deafness in llamas (Lama glama) and alpacas (L. pacos)

Auditory function of llamas and alpacas was assessed objectively by means of brainstem auditory-evoked response audiometry (BAER) to establish the normal hearing range and to test the hypothesis of a correlation between blue eyes, white coat, and deafness. Sixty-three camelids were available for the study. Thirteen animals had blue irides; 1 animal had 1 blue and 1 pigmented iris. Wave latencies, amplitudes, and interpeak latencies were measured under general anesthetic. Click stimuli (dB [HL]) were delivered by an insert earphone. Four to five positive peaks could be detected; waves I, II, and V were reproducible; wave II appeared infrequently; and wave IV generally merged with wave V to form a complex. Peak latencies decreased and peak amplitudes increased as stimulus intensity increased. A hearing threshold level of 10-20 dB (HL) was proposed as the normal range in llamas and alpacas. None of the animals with pigmentation of coat and iris showed any degree of hearing impairment. Seven of the 10 blue-eyed, pure-white animals were bilaterally deaf and one of them was unilaterally deaf. However, 2 blue-eyed, white animals exhibited normal hearing ability. Three blue-eyed animals with pigmented coat did not show any hearing impairment. All white animals with normal iris pigmentation had normal auditory function; so did the 1 animal with 1 normal and 1 blue iris. The high frequency (78%) of bilaterally deaf animals with pure white coat and blue iris pigmentation supports the hypothesis of a correlation between pigmentation anomalies and congenital deafness in llamas and alpacas.     

Microsatellite marker C04107 as a diagnostic marker for copper toxicosis in the Danish population of Bedlington terriers

The linkage phase of marker C04107 was evaluated before implementation of the marker in a diagnostic test. Blood samples from 68 dogs were collected and genotyped by PCR. Two alleles were detected with sizes of 160 bp and 164 bp and allele frequencies of 0.45 and 0.55 respectively. Genotyping revealed that 35 dogs were heterozygous (51.5%), 22 dogs were homozygous for the normal allele (32.3%) and 11 dogs were homozygous for the disease allele (16.2%). Liver biopsies were taken from 14 selected dogs and the copper content was evaluated histologically. Biopsies from 8 dogs homozygous for the disease allele showed many copper granules along with single cell necrosis, haemosiderosis and cellular infiltration. In liver biopsies from 6 dogs genotyped to be heterozygous or homozygous for the normal allele, copper granules were absent or moderate in number and no lesions were present. The survey demonstrates that the linkage phase of marker C04107 in the Danish population of Bedlington terriers is similar to the linkage phase detected in other countries. Thus, the marker can be used in a diagnostic test for copper toxicosis in Denmark.     

Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog.

Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had >9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.     

Does a pleiotropic gene explain deafness and blue irises in white cats?

The prevalence of deafness is high in cat populations in which the dominant white gene is segregating. The objective of this study was to investigate whether there is a gene that is responsible for deafness as well as for blue eyes and to establish a plausible mode of inheritance. For this purpose, data from an experimental colony with deaf cats were analyzed. The hearing status was determined by acoustically evoked brain stem responses (BAER). Complex segregation analyses were conducted to find out the most probable mode of inheritance using maximum likelihood procedures. The prevalence of deafness and partial hearing in the experimental colony was 67% and 29%, respectively. The results of the bivariate segregation analysis support the hypothesis of a pleiotropic major gene segregating for deafness and blue iris colour. The high heritability coefficients for both traits, 0.55 and 0.75 respectively, indicate that beside the major gene there is an important influence of polygenic effects.     

Erythrocytic pyruvate kinase deficiency and AB blood types in Australian Abyssinian and Somali cats

Objective   To determine the frequency of the mutant pyruvate kinase (PK) allele, haematological parameters and AB blood types of Abyssinian and Somali cats in Australia.
Design   Complete blood cell and reticulocyte counts, DNA PK mutation testing and blood typing were performed in all cats.
Results   A total of 60 cats (36 Abyssinians, 24 Somalis) were included (37 females, 23 males). For the mutant PK allele, three female Somalis were homozygous (affected, 5%), 17 cats were heterozygous (carrier, 28%) and 40 cats tested negative (normal, 67%). Pedigree analysis revealed common ancestry of affected and many carrier cats. Of affected cats, two had regenerative anaemias and all had reticulocytosis (range 64–390 × 10⁹/L; P < 0.001 compared with normal or carrier cats). The only consistent historical sign was lethargy. One affected cat was euthanased 18 months after testing, because of anaemia, neutropenia, anorexia and weight loss. The mutant allele frequency was 0.19 overall (0.29 in Somalis, 0.13 in Abyssinians). All cats had blood type A. The commercial blood typing card method incorrectly identified 12 cats as having type AB blood.
Conclusions    The frequency of the mutant PK allele is high in Australia. Screening for PK deficiency is indicated before mating and in individual cats of these breeds, even in the absence of anaemia and especially when there is reticulocytosis. Although all cats in the present study had blood type A, blood type B is common in these breeds worldwide. Retyping of any AB typed cats by a laboratory technique is recommended.     

Inheritance of von Willebrand's disease in a colony of Doberman Pinschers

OBJECTIVE: To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. ANIMALS: 159 Doberman Pinschers. PROCEDURE: von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low (< 20%), intermediate (20 to 65%), or high (> 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. RESULTS: von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.     

Lens-induced uveitis in dogs: 151 cases (1985-1990).

During a 5-year period, phacolytic uveitis was diagnosed in 202 eyes of 151 dogs admitted to the veterinary teaching hospital. The diagnosis of phacolytic uveitis was based on the finding of a cataractous lens and anterior uveitis, unassociated with other identifiable causes of uveal inflammation. The most commonly affected breeds were the Toy and Miniature Poodle (35%) and the American Cocker Spaniel (19%). The mean age was 7.0 years for all breeds, 5.1 years for the Cocker Spaniel, and 9.0 years for the Poodle breeds. Evidence of cataract resorption was visible in 72% of the eyes. Fifty-one dogs were affected bilaterally and 100 dogs unilaterally. The mean interval between recognition of the cataract and the onset of lens-induced uveitis (LIU) was 17 months; mean times of 25 and 11 months were seen in the Poodle breeds and American Cocker Spaniel, respectively. The mean age of dogs requiring greater than 1 revisit before the inflammation had subsided was 5.5 years. Complications, referable to the uveitis, were seen in 14% of eyes, the most important of which were glaucoma (16 eyes) and phthisis bulbi (9 eyes). Lens extraction surgery was done on 50 LIU-affected eyes, and on 35 normal eyes in LIU-affected animals. The 2- and 6-month success rates for LIU-affected eyes were 78 and 39%, respectively, and for normal eyes in LIU-affected animals were 85 and 71%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)