Hydrops fetalis caused by a complex congenital heart defect with concurrent hypoplasia of pulmonary blood vessels and lungs visualized by micro-CT in a French Bulldog.

BACKGROUND: Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified. CASE PRESENTATION: A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed. CONCLUSIONS: This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.

Relationship between clinical parameters and malformations in dogs diagnosed with atlanto-axial instability.

Atlanto-axial instability is a common disease that affects toy-breed dogs. Most cases of atlanto-axial instability are congenital. Furthermore, patients with atlanto-axial instability are predisposed to other concurrent diseases. Therefore, this study aimed to retrospectively determine the presence of concurrent diseases in cases with atlanto-axial instability using imaging data and analyze the relationship between clinical parameters and the incidence of complex malformations. The clinical data and imaging findings of 41 toy-breed dogs diagnosed with atlanto-axial instability were analyzed using their medical records and imaging data. Occipital dysplasia (17/27), atlanto-occipital overlapping (22/34), dens dysplasia (27/41), Chiari-like malformation (8/34), syringomyelia (5/34), lateral ventricular enlargement (20/36), and intracranial arachnoid cyst (5/35) were observed in patients with atlanto-axial instability. The body weight of the patients in the groups with atlanto-occipital overlapping and lateral ventricular enlargement was lower than that of those in the groups without these diseases (1.78 ± 0.71 vs 2.71 ± 1.15 kg, P = 0.0269, 1.60 ± 0.40 vs 2.75 ± 1.08 kg, P = 0.001, respectively). Furthermore, when the correlation between the total number of concurrent diseases and the age at onset and body weight was examined, it became clear that lower body weight was associated with the incidence of a greater number of concurrent diseases. Thus, the findings of this study suggest that toy-breed dogs are more likely to present with complex malformations and should be evaluated carefully with additional examinations and treatment methods.

Enlargement of the hepatic artery is present in dogs with a congenital extrahepatic portosystemic shunt and is independent of shunt insertion into the systemic circulation.

The accurate diagnosis of portovascular anomalies has been facilitated by improvements in diagnostic imaging technology. In humans, hepatic arterial blood flow changes in response to the reduction in portal blood flow. The hepatic arterial buffer response characterizes an intrinsic regulatory mechanism in response to reduced portal venous blood flow, which results in hepatic arterial enlargement. At the authors' institution, enlargement of the hepatic artery has been anecdotally observed in a population of dogs with extrahepatic portosystemic shunting, consistent with previous literature that documents variability in hepatic arterial size. In this retrospective, blinded, analytical study, a hepatic artery:aorta (Ha:Ao) ratio was assessed on CT studies from 112 dogs, with (n = 43) and without (n = 69) an extrahepatic congenital portosystemic shunt in order to compare the hepatic artery size independent of body weight between the two populations. A significant increase in the Ha:Ao ratio was documented in dogs with an extrahepatic portosystemic shunt (EHPSS) compared with those dogs with no EHPSS independent of the location of shunt insertion into the systemic circulation (P < .001). Three cases had repeat CT after surgery, and all had Ha:Ao ratio reductions following treatment. The authors propose that this may be an additional imaging feature observed in dogs with an EHPSS.

Anomalous origin of the right coronary artery from the pulmonary artery in a Staffordshire bull terrier.

An asymptomatic 17-month-old, 18.5-kg, male Staffordshire bull terrier was referred due to a heart murmur. Examination revealed a grade 3/6 left apical systolic and right apical 3/6 heart murmur. Echocardiography showed volume overload of the left ventricle and mild systolic dysfunction with a left-right flow over the interventricular septal region. Cardiac gated computed tomography revealed anomalous origin of the right coronary artery from the pulmonary artery, an extensive network of collateral blood vessels connected the right and left coronary arteries, with bronchial and left intercostal arteries also connected to the network of collateral blood vessels, markedly enlarged right and left coronary arteries and left coronary sinus. With varied presentation, coronary anomalies are difficult to recognise and classify and to the best of our knowledge this is the first case of anomalous origin of the right coronary artery from the pulmonary artery diagnosis in the dog.

Intramural esophageal location of a portosystemic shunt in a dog with two congenital portosystemic shunts on CT angiography.

A 5-year-old male neutered pug with hematuria was presented to a referral hospital after identification of an extrahepatic portosystemic shunt (EHPSS) during abdominal ultrasonography. Computed tomographic-angiography revealed two anomalous blood vessels (left gastroazygous and left gastrophrenic). The left gastroazygous vessel followed an atypical path within the dorsolateral esophageal wall before entering the azygous vein. The morphology of this highly unusual vessel has not, based on the authors' review of the literature, been previously reported. In combination with a second anomalous vessel, this resulted in a unique presentation of an EHPSS. Computed tomography-angiography was essential for diagnosis and surgical planning in this case.

Congenital ventricular outflow tract obstructions in Boxer dogs: Results of a 17-year cardiovascular breed screening program in France (3126 dogs).

INTRODUCTION: Ventricular outflow tract obstructions including aortic (AS) and pulmonic stenosis (PS) are the most common canine congenital heart diseases, with Boxer dogs being predominantly affected. This has led to the French Boxer club adopting a mandatory national control program against AS and PS. The objective of this retrospective study was to analyze the results of 17 years of this cardiovascular breed screening program (2005-2021). MATERIALS AND METHODS: The records of untreated and non-anesthetized adult Boxer dogs screened between 2005 and 2021 were retrospectively reviewed. All dogs underwent physical examination and standard transthoracic echocardiography with concomitant ECG tracing. All examinations were reviewed by one single board-certified specialist in cardiology. RESULTS: Out of the 3126 dogs screened during the study period, 3001 dogs (female:male sex ratio = 2.2, median age [IQR] = 1.6 years [1.2-2.1]) were recruited for data analysis. A total of 218 operators were involved in the screening program. For most Boxer dogs (i.e., 93.8% for AS and 94.5% for PS), a single examination was required to obtain a definitive cardiac status, although most operators were non-specialist general practitioners. A left basilar systolic heart murmur was detected in all dogs with AS and PS, but also in 7.4% dogs free of heart diseases. A significantly higher proportion of the latter was detected when operators were board-certified specialists (P<0.001). Lastly, when comparing the start and the end of the breeding program, among dogs diagnosed with AS and PS (n = 364) in a French referral cardiology center, Boxer went from the 1st affected breed by AS to the 3rd, and from the 3rd affected breed by PS to the 6th. CONCLUSION: This 17-year screening program has experienced a strong involvement of veterinarians, breeders, and owners throughout France. This may have contributed to reduce AS and PS prevalence in Boxer dogs at the studied referral cardiology center.

Dogs with congenital extrahepatic portosystemic shunts that have persistent shunting after surgery have a higher prevalence of urolithiasis.

OBJECTIVE: To report the presence of urolithiasis in dogs long-term after gradual attenuation of congenital extrahepatic portosystemic shunts (cEHPSS). ANIMALS: 25 client-owned dogs that underwent gradual attenuation of a cEHPSS, of which 19 had a closed cEHPSS and 6 developed multiple acquired portosystemic shunts (MAPSS) following surgery. PROCEDURES: A retrospective study with prospective follow-up was performed. Dogs that underwent cEHPSS surgery and had their postoperative cEHPSS status determined by transsplenic portal scintigraphy or CT angiography 3 months postoperatively were prospectively contacted and invited for a long-term follow-up visit (a minimum of 6 months postoperatively). Retrospective data were collected, and during the prospective follow-up visit a thorough history, blood tests and urinalysis, and ultrasonography of the urinary tract were performed to assess the presence of urinary signs and urolithiasis. RESULTS: Of 25 included dogs, 1 of 19 (5%) dogs with closed cEHPSS and 4 of 6 (67%) dogs with MAPSS had urolithiasis at long-term follow-up. Three (50%) dogs with MAPSS developed new uroliths. Long-term, dogs with closed cEHPSS that initially presented with and without urolithiasis had significantly less urolithiasis compared to dogs with MAPSS (P = .013 and P = .010, respectively). In the 4 dogs with closed cEHPSS that initially presented with nephrolithiasis, nephroliths became smaller or were no longer visible at the long-term follow-up visit. CLINICAL RELEVANCE: Dogs that developed MAPSS following cEHPSS surgery are at greater risk of urolithiasis compared to those with closed cEHPSS. Furthermore, ammonium urate uroliths might dissolve if portosystemic shunting ceases to exist.

A novel surgical treatment of type 3 congenital elbow luxation in a dog.

Congenital luxation of the ulnar and radius is a rare orthopaedic condition in the dog. This case report describes a novel surgical treatment for congenital elbow luxation in a medium-breed dog. A 6-week-old Kelpie presented for left forelimb lameness and deformity. Radiographs and computed tomography (CT) confirmed the diagnosis of unilateral ulnar and radius luxation. The surgical repair involved open reduction followed by fixation with an extraarticular pin and a transarticular external fixator. The outcome of surgery was improved leg function and weight-bearing, however, reluxation of the radial head was diagnosed 7 weeks following surgery. This technique may offer an alternative surgical option to improve clinical signs, as well as insight into improving the management of this condition.

Integrative echocardiographic assessment of post-operative obstruction severity and restenosis after balloon valvuloplasty in 81 dogs with pulmonary stenosis.

INTRODUCTION/OBJECTIVES: Pulmonary stenosis (PS) is a congenital defect in the dog that is managed with balloon valvuloplasty (BV). Obstruction severity is routinely assessed using transthoracic echocardiography. The objectives of this study were to describe the short-term changes and long-term restenosis by retrospectively evaluating flow-dependent and flow-independent echocardiographic variables for dogs with PS after BV. ANIMALS, MATERIALS, AND METHODS: Medical records and stored echocardiographic images were reviewed from dogs that received BV for PS. The following echocardiographic variables were measured or calculated: maximum systolic ejection velocity (VmaxPV) and velocity-derived maximal pressure gradient (PV maxPG) across the pulmonary valve; ratio of aortic to pulmonary velocity time integral (VTIAV/VTIPV); ratio of aortic to pulmonary maximal velocity. RESULTS: Eighty-one dogs with PS that had a BV were included. Each of these dogs had pulmonary obstruction severity assessed in at least three timepoints. Forty-nine dogs had at least one additional examination performed, the last of which occurred a median of 504 days after the BV. Echocardiographic variables at the first follow-up had increased by a clinically relevant quantity in 20-34% of the dogs when comparing to the immediate post-BV examination. The last follow-up examination identified valve restenosis in 18-38% of the dogs in this study. Valve type and pre-BV obstruction severity did not have a significant effect (P > 0.1). CONCLUSIONS: For the assessment of BV efficacy, the immediate post-BV echocardiogram may not be as useful as the first follow-up examination several months later. Pulmonary restenosis after BV may be more prevalent than previously reported.

Short- and long-term outcomes of polyethylene band attenuation of congenital extrahepatic portosystemic shunts in dogs: 60 cases (2010-2020).

OBJECTIVES: To report the short- and long-term outcomes following attenuation of congenital extrahepatic portosystemic shunts in dogs using a novel polyethylene band. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent congenital extrahepatic portosystemic shunt attenuation by a polyethylene banding technique, at a single institution between 2010 and 2020. Short-term outcome data were collected from peri-operative clinical records with follow-up examinations, scheduled at 6 and 18 weeks post-operatively, and post-operative imaging when performed. Long-term follow-up was collected by validated owner questionnaire, telephone interview or medical records. Long-term outcomes were categorised by "excellent", "good" or "poor". RESULTS: Sixty dogs were included. Post-operative complications occurred in 10 of 60 dogs (16.7%), four major and six minor, with a peri-operative mortality of 6.7%. Persistent shunting was identified in nine of 53 dogs (17%) available for follow-up examination and four dogs underwent a revision surgery. Long-term follow-up was available for 44 dogs at a median of 75 months post-operatively (range 7 to 128). Long-term outcomes were "excellent" (26) or "good" (8) in 81.8% of dogs and "poor" (8) in 18.2%. At the time of follow-up, 30 of 44 (68.2%) dogs were not receiving any medical treatment and 27 of 28 (96.4%) questionnaire respondents were satisfied with the response to surgery. CLINICAL SIGNIFICANCE: Polyethylene band attenuation of congenital extrahepatic portosystemic shunts provides comparable outcomes to cellophane. The material used in this study is widely available and consistent while being pre-sterilised and pre-folded makes it easy to use.

Comparison of diet, lactulose, and metronidazole combinations in the control of pre-surgical clinical signs in dogs with congenital extrahepatic portosystemic shunts.

BACKGROUND: Hepatic supportive diet (HSD), lactulose, and antimicrobials are medical treatments for dogs with congenital extrahepatic portosystemic shunts (cEHPSS). The relative contribution of these treatment components is currently unknown. OBJECTIVES: To determine which treatment combinations are most efficacious in pre-surgical control of clinical signs of cEHPSS in dogs. ANIMALS: Thirty-six dogs with untreated cEHPSS. METHODS: Three-arm randomized clinical trial. At inclusion (T0), dogs were divided into 3 groups: HSD (n = 12), HSD + lactulose (n = 12), or HSD + metronidazole (n = 12) and received the randomized treatment for 4 weeks (T1) followed by combined treatment of HSD + lactulose + metronidazole for 2 weeks or until cEHPSS attenuation (T2). Clinical score as well as fasting ammonia (FA) and C-reactive protein (CRP) concentrations were compared among groups and time points. RESULTS: Thirty-four dogs were evaluated. Thirty-four dogs reached T1 and 29 dogs T2. At T1, clinical scores decreased in the HSD + lactulose (n = 11; P = .001), but not in the HSD (n = 8; P = .96) and HSD + metronidazole (n = 10; P = .06) groups. Adding metronidazole to HSD + lactulose (n = 11) did not result in further clinical score improvement (T2; P = 1.000). Moderate and weak correlation between clinical score and FA and clinical score and CRP was present (ρ = .35, P < .001; ρ = .27, P = .01, respectively) with FA decreasing over time on medical treatment (P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Combined HSD + lactulose seems sufficient for pre-surgical cEHPSS stabilization unlike sole HSD or HSD + metronidazole. Medical treatment of cEHPSS clinical signs decreases FA.

Long-term palliation of right-sided congestive heart failure after stenting a recurrent cor triatriatum dexter in a 10½-year-old pug.

A 10½-year-old, male neutered, pug presented with increasing ascites over two months. Echocardiography revealed cor triatriatum dexter with no concurrent cardiovascular anomalies, subsequently confirmed by computed tomography angiography. Balloon dilation of the perforated intra-atrial membrane under fluoroscopic guidance resulted in the transient resolution of all clinical abnormalities, but six months later stenosis and ascites recurred. After repeated balloon dilation, a stent was placed across the membrane. The dog remains asymptomatic fourteen months after the second procedure. One noteworthy feature of this case is the onset of congestive heart failure due to a congenital defect only at more than 10 years of age.

Laparoscopic portosystemic shunt attenuation in 20 dogs (2018-2021).

OBJECTIVE: To describe the technique, complications, and outcome of laparoscopic portosystemic shunt attenuation (LPSSA) in dogs. STUDY DESIGN: Retrospective study. ANIMALS: Twenty client-owned dogs. METHODS: Medical records were searched for dogs with a single congenital extrahepatic portosystemic shunt (CEPSS) that was treated with LPSSA. Signalment, clinical signs, CEPSS location, diagnostic imaging, laparoscopic approach, operative technique, complications, and clinical outcome were reviewed. RESULTS: Fourteen dogs with CEPSS located in the epiploic foramen had a right (13/14) or left (1/14) paramedian approach. In 6 dogs a CEPSS was not located in the epiploic foramen, and a left paramedian approach was used. A 3 or 4-port technique was used in 7 and 13 dogs, respectively. A thin film band was used for CEPSS attenuation in all dogs. The median operating time for LPSSA was 62 min (range 27-98 min). Intraoperative complications requiring conversion to an open technique occurred in 5 dogs. Mild perioperative self-limiting portal hypertension occurred in 3 dogs, while severe portal hypertension with surgical revision occurred in 1 case. The complications were resolved, and all dogs had a good outcome. CONCLUSION: Laparoscopic portosystemic shunt attenuation can be performed in dogs, in particular for a CEPSS located in the epiploic foramen using a right paramedian approach. For CEPSS not located in the epiploic foramen, a left paramedian approach is recommended. Conversion to open celiotomy was required in around a third of cases. CLINICAL SIGNIFICANCE: Laparoscopic attenuation of CEPSSs can be performed in dogs and has a good clinical outcome, particularly for CEPSS located in the epiploic foramen.

Successful ligation of the left and right gastric vein in a dog with congenital portosystemic shunts type Aii.

The type Aii shunt is a congenital extrahepatic portosystemic shunt (ePSS) involving the left and right gastric vein and the caudal vena cava (CVC). This report describes the case of a 6-month-old Italian greyhound diagnosed with a type Aii large-diameter ePSS. Staged surgeries were employed to completely ligate the 2 gastric veins and to avoid the risk of traumatizing the shunt vessel, CVC, and celiac artery. Clinical signs improved postoperatively, and after 3 years, ultrasonography demonstrated no evidence of reoccurrence. This procedure provides an alternative surgical option for correction of ePSS type Aii. Key clinical message: This case report demonstrates congenital PSS involving the left and right gastric vein and the caudal vena could be treated with both ligation of left and right gastric vein. This technique could decrease the risk of traumatizing the shunt vessel, CVC, and celiac artery.

Ligature réussie des veines gastriques gauche et droite chez un chien avec des shunts portosystémiques congénitaux de type Aii. Le shunt de type Aii est un shunt porto-systémique extrahépatique congénital (ePSS) impliquant la veine gastrique gauche et droite et la veine cave caudale (CVC). Ce rapport décrit le cas d'un lévrier italien de 6 mois diagnostiqué avec un ePSS de grand diamètre de type Aii. Des chirurgies par étapes ont été effectuées pour ligaturer complètement les deux veines gastriques et pour éviter le risque de traumatiser le vaisseau avec shunt, la CVC et l'artère coeliaque. Les signes cliniques se sont améliorés après l'opération et après trois ans, l'échographie n'a montré aucun signe de récidive. Cette procédure offre une option chirurgicale alternative pour la correction de l'ePSS de type Aii.Message clinique clé :Ce rapport de cas démontre un ePSS congénital impliquant la veine gastrique gauche et droite et la veine caudale pouvant être traité par la ligature de la veine gastrique gauche et droite. Cette technique pourrait diminuer le risque de traumatiser le vaisseau avec shunt, le CVC et l'artère coeliaque.(Traduit par Dr Serge Messier).

Updates in Hepatobiliary Surgery: New Data on Portosystemic Shunts and Cholecystectomy in Dogs and Cats.

Advances regarding surgical treatment of hepatobiliary diseases over the past 5 years have resulted in improved outcomes and decreased mortality in veterinary patients. Options for minimally invasive treatment of intrahepatic portosystemic shunts and gallbladder disease have led to decreased morbidity with similar outcomes to open procedures. For extrahepatic portosystemic shunts, studies evaluating long-term outcome between surgical attenuation and medical management, as well as between options for surgical attenuation, are being used to direct evidence-based treatment of this congenital anomaly. In addition, evaluation of timing in surgical intervention for gallbladder mucoceles has led to an opportunity for decreased mortality rates after cholecystectomy.

Long-term outcome and quality of life of dogs that developed neurologic signs after surgical treatment of a congenital portosystemic shunt: 50 cases (2005-2020).

OBJECTIVE: To determine survival time and quality of life of dogs that developed postattenuation neurologic signs (PANS) after surgical treatment of a single congenital portosystemic shunt and survived at least 30 days and identify whether neurologic signs present at the time of discharge would resolve or reoccur. ANIMALS: 50 client-owned dogs. PROCEDURES: Medical records were retrospectively reviewed, and follow-up data relating to neurologic signs and seizure activity were obtained. Owners were asked to complete a questionnaire related to the presence of neurologic signs, including seizures, and their dog's quality of life. RESULTS: Thirty of the 50 (60%) dogs had postattenuation seizures with or without other nonseizure neurologic signs, and 20 (40%) had neurologic signs other than seizures. Neurologic signs had fully resolved by the time of discharge in 24 (48%) dogs. Signs resolved in 18 of the remaining 26 (69%) dogs that still had PANS other than seizures at the time of discharge. Seizures reoccurred in 15 of the 30 dogs that had postattenuation seizures. Twenty-seven of 33 (82%) owners graded their dog's long-term (> 30 days after surgery) quality-of-life as high. Forty-five (90%) dogs survived > 6 months. Most (29/43 [67%]) neurologic signs (other than seizures) present at the time of hospital discharge resolved. CLINICAL RELEVANCE: Findings highlighted that survival times of > 6 months and a high QOL can be achieved in most dogs with PANS that survive at least 30 days. Most neurologic signs other than seizures resolved within 1 month postoperatively. Half of the dogs with postattenuation seizures had a reoccurrence.

Serum insulin-like growth factor-1 as a marker of improved liver function and surgical outcome in dogs with congenital extrahepatic portosystemic shunts.

Serum insulin-like growth factor-1 concentration (sIGF-1c) is reduced in various hepatopathies in humans and dogs. This work aimed to evaluate sIGF-1c in dogs before and after congenital extrahepatic portosystemic shunt (cEHPSS) attenuation, in relation to surgical outcome (closed vs. persistent shunting). Secondarily, it aimed to assess if sIGF-1c can discriminate between cEHPSS and portal vein hypoplasia (PVH) and finally compare sIGF-1c ratio (postoperative/preoperative sIGF-1c) to pre-prandial serum bile acids (preBA), post-prandial bile acids (postBA), bile acid stimulation test (BAST) and fasting ammonia (FA), regarding surgical outcome. Thirty-nine dogs were included: 15 with closed cEHPSS, 15 with persistent shunting and nine with PVH. Transplenic portal scintigraphy was used to classifiy surgical outcome. There was no significant difference in sIGF-1c between dogs with cEHPSS and those with PVH (P > 0.05). Postoperative sIGF-1c increased in all dogs (P < 0.001 and P = 0.023 for closed and persistent shunting, respectively) and the increase was more pronounced in closed cEHPSS than in persistent shunting (P = 0.006). Using an optimal sIGF-1c ratio cut-off of 2.23, the sensitivity was 93.3% and the specificity was 66.7% for differentiation between surgical outcomes. Serum pre-prandial bile acids, postBA BAST and FA had sensitivities of 80%, 86.7%, 86.7%, 60%; and specificities of 100%, 93.3%, 93.3%, 100%, respectively. There was a greater increase in sIGF-1c after shunt closure than during persistent shunting; nevertheless sIGF-1c ratio was inferior to advanced imaging to assess surgical outcome.

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.

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.

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.