Congenital block vertebrae and intervertebral disc protrusion in a young cat.

CASE SUMMARY: A 6-month-old domestic shorthair cat was evaluated for proprioceptive ataxia of the pelvic limbs. Over 2 months, the cat became poorly ambulatory, paraparetic with proprioceptive ataxia and developed a firm, distended bladder with intermittent overflow urinary incontinence. Block vertebrae (T1-3, T4-5 and T10-11) and lordosis were identified on radiographs of the vertebral column. MRI revealed T3/4 intervertebral disc protrusion with severe extradural compression, secondary syringohydromyelia caudal to the protrusion and generalised intervertebral disc disease throughout the cervical and thoracic vertebrae. Dorsal laminectomy at T3/4 resulted in resolution of paraparesis and marked improvement in coordination and strength. Block vertebrae are usually considered an incidental finding. In this patient, angular deformation (lordosis) and adjacent segment disease probably contributed to clinically significant intervertebral disc degeneration and protrusion. RELEVANCE AND NOVEL INFORMATION: There are few case reports in the literature of multiple congenital vertebral malformations causing neurological deficits in cats. This is the first reported case of successful surgical management of intervertebral disc protrusion, possibly secondary to block vertebrae and lordosis in a cat.

Consequences and Management of Canine Brachycephaly in Veterinary Practice: Perspectives from Australian Veterinarians and Veterinary Specialists.

This article, written by veterinarians whose caseloads include brachycephalic dogs, argues that there is now widespread evidence documenting a link between extreme brachycephalic phenotypes and chronic disease, which compromises canine welfare. This paper is divided into nine sections exploring the breadth of the impact of brachycephaly on the incidence of disease, as indicated by pet insurance claims data from an Australian pet insurance provider, the stabilization of respiratory distress associated with brachycephalic obstructive airway syndrome (BOAS), challenges associated with sedation and the anaesthesia of patients with BOAS; effects of brachycephaly on the brain and associated neurological conditions, dermatological conditions associated with brachycephalic breeds, and other conditions, including ophthalmic and orthopedic conditions, and behavioural consequences of brachycephaly. In the light of this information, we discuss the ethical challenges that are associated with brachycephalic breeds, and the role of the veterinarian. In summary, dogs with BOAS do not enjoy freedom from discomfort, nor freedom from pain, injury, and disease, and they do not enjoy the freedom to express normal behaviour. According to both deontological and utilitarian ethical frameworks, the breeding of dogs with BOAS cannot be justified, and further, cannot be recommended, and indeed, should be discouraged by veterinarians.

Exercise-induced hyperthermia syndrome (canine stress syndrome) in four related male English springer spaniels.

OBJECTIVE: This retrospective study describes the signalment, clinical presentation, diagnostic findings, and mode of inheritance in four young male English springer spaniel dogs with presumptive canine stress syndrome. MATERIALS AND METHODS: Appropriate cases were located through medical searches of medical records of two large private referral centers. Inclusion criteria comprised of English springer spaniel dogs with tachypnea and hyperthermia that subsequently developed weakness or collapse, with or without signs of hemorrhage, soon after a period of mild-to-moderate exercise. The pedigrees of the four affected dogs, as well as eleven related English springer spaniels, were then analyzed to determine a presumptive mode of genetic inheritance. RESULTS: Four dogs met the inclusion criteria. All four were male, suggesting the possibility of a recessive sex-linked heritable disorder. Pedigree analysis suggests that more dogs may be potentially affected, although these dogs may have never had the concurrent triggering drug/activity/event to precipitate the clinical syndrome. There was complete resolution of clinical signs in three of the four dogs with aggressive symptomatic and supportive therapy, with one dog dying during treatment. CONCLUSION: Dogs with canine stress syndrome have the potential for rapid recovery if treated aggressively and the complications of the disease (eg, coagulopathy) are anticipated. All four dogs were male, suggesting the possibility of a recessive sex-linked mode of inheritance. Further genetic analyses should be strongly considered by those involved with the English springer spaniel breed, either with a genome-wide association study using canine single-nucleotide polymorphism arrays or whole-genome sequencing of affected and closely related dogs.

Congenital vestibular disease in captive Sumatran tigers (Panthera tigris ssp. sumatrae) in Australasia.

The Sumatran tiger (Panthera tigris ssp. sumatrae) is a critically endangered species in the wild. To ensure that demographic and genetic integrity are maintained in the longer term, those Sumatran tigers held in captivity are managed as a global population under a World Association of Zoos and Aquariums Global Species Management Plan (GSMP). A retrospective study, including segregation and pedigree analysis, was conducted to investigate potential cases of congenital vestibular disease (CVD) in captive Sumatran tigers in Australasian zoos using medical and husbandry records, as well as video footage obtained from 50 tigers between 1975 and 2013. Data from the GSMP Sumatran tiger studbook were made available for pedigree and segregation analysis. Fourteen cases of CVD in 13 Sumatran tiger cubs and one hybrid cub (Panthera tigris ssp. sumatrae × Panthera tigris) were identified. Vestibular signs including head tilt, circling, ataxia, strabismus and nystagmus were observed between birth and 2 months of age. These clinical signs persisted for a median of 237 days and had resolved by 2 years of age in all cases. Pedigree analysis revealed that all affected tigers were closely related and shared a single common ancestor in the last four generations. A genetic cause for the disease is suspected and, based on pedigree and segregation analysis, an autosomal dominant mode of inheritance is likely. Further investigations to determine the world-wide prevalence and underlying pathology of this disorder are warranted.

X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene.

BACKGROUND: Congenital and inherited myopathies in dogs are faithful models of human muscle diseases and are being recognized with increasing frequency. In fact, canine models of dystrophin deficient muscular dystrophy and X-linked myotubular myopathy are of tremendous value in the translation of new and promising therapies for the treatment of these diseases. We have recently identified a family of Australian Rottweilers in which male puppies were clinically affected with severe muscle weakness and atrophy that resulted in early euthanasia or death. X-linked myotubular myopathy was suspected based on the early and severe clinical presentation and histopathological changes within muscle biopsies. The aim of this study was to determine the genetic basis for myopathy in these dogs and compare and contrast the clinical presentation, histopathology, ultrastructure, and mutation in this family of Rottweiler dogs with the previously described myotubular myopathy in Labrador retrievers. RESULTS: Histopathology, histochemistry, and ultrastructural examination of muscle biopsies from affected Rottweiler puppies were consistent with an X-linked myotubular myopathy. An unusual finding that differed from the previously reported Labradors and similar human cases was the presence of excessive autophagy and prominent autophagic vacuoles. Molecular investigations confirmed a missense mutation in exon 11 of MTM1 that was predicted to result in a non-functional phosphatase activity. Although the clinical presentations and histopathology were similar, the MTM1 p.(Q384P) mutation is different from the p.(N155K) mutation in exon 7 affecting Labrador retrievers with X-linked myotubular myopathy. CONCLUSIONS: Here we describe a second pathogenic mutation in MTM1 causing X-linked myotubular myopathy in dogs. Our findings suggest a variety of MTM1 mutations in dogs as seen in human patients. The number of MTM1 mutations resulting in similar severe and progressive clinical myopathy and histopathological changes are likely to increase as canine myopathies are further characterized.

Quantitative trait loci (QTL) study identifies novel genomic regions associated to Chiari-like malformation in Griffon Bruxellois dogs.

Chiari-like malformation (CM) is a developmental abnormality of the craniocervical junction that is common in the Griffon Bruxellois (GB) breed with an estimated prevalence of 65%. This disease is characterized by overcrowding of the neural parenchyma at the craniocervical junction and disturbance of cerebrospinal fluid (CSF) flow. The most common clinical sign is pain either as a direct consequence of CM or neuropathic pain as a consequence of secondary syringomyelia. The etiology of CM remains unknown but genetic factors play an important role. To investigate the genetic complexity of the disease, a quantitative trait locus (QTL) approach was adopted. A total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Six traits were found to be associated to CM and were subjected to a whole-genome association study using the Illumina canine high density bead chip in 74 GB dogs (50 affected and 24 controls). Linear and mixed regression analyses identified associated single nucleotide polymorphisms (SNPs) on 5 Canis Familiaris Autosomes (CFAs): CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb on CFA2 strongly associated to the height of the cranial fossa (diameter F) and an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part of the caudal cranial fossa (AE) and the height of the brain (FG) were significantly associated to CM after 10 000 permutations strengthening their candidacy for this disease (P = 0.0421, P = 0.0094 respectively). The CFA2 QTL harbours the Sall-1 gene which is an excellent candidate since its orthologue in humans is mutated in Townes-Brocks syndrome which has previously been associated to Chiari malformation I. Our study demonstrates the implication of multiple traits in the etiology of CM and has successfully identified two new QTL associated to CM and a potential candidate gene.

Empirical assessment of competitive hybridization and noise in ultra high density canine tiling arrays.

BACKGROUND: In addition to probe sequence characteristics, noise in hybridization array data is thought to be influenced by competitive hybridization between probes tiled at high densities. Empirical evaluation of competitive hybridization and an estimation of what other non-sequence related features might affect noisy data is currently lacking. RESULTS: A high density array was designed to a 1.5 megabase region of the canine genome to explore the potential for probe competition to introduce noise. Multivariate assessment of the influence of probe, segment and design characteristics on hybridization intensity demonstrate that whilst increased density significantly depresses fluorescence intensities, this effect is largely consistent when an ultra high density offset is applied. Signal variation not attributable to sequence composition resulted from the reduction in competition when large inter-probe spacing was introduced due to long repetitive elements and when a lower density offset was applied. Tiling of probes immediately adjacent to various classes of repeat elements did not generate noise. Comparison of identical probe sets hybridized with DNA extracted from blood or saliva establishes salivary DNA as a source of noise. CONCLUSIONS: This analysis demonstrates the occurrence of competitive hybridization between oligonucleotide probes in high density tiling arrays. It supports that probe competition does not generate random noise when it is maintained across a region. To prevent the introduction of noise from this source, the degree of competition should be regulated by minimizing variation in density across the target region. This finding can make an important contribution to optimizing coverage whilst minimizing sources of noise in the design of high density tiling arrays.

Myelitis due to reactivated spinal toxoplasmosis in a cat.

The diagnosis, management, and subsequent post-mortem confirmation of a case of suspected reactivated spinal toxoplasmosis in a 10-year-old female neutered Cornish Rex are described. While an ante-mortem diagnosis of toxoplasmosis was considered possible based on the neuroanatomical diagnosis of central nervous system (CNS) disease primarily involving spinal cord segment C6-T2 and the progressive elimination of other potential causes, Toxoplasma gondii antibody titres were consistent with previous exposure rather than active infection. A poor response to appropriate therapy did not support a diagnosis of toxoplasmosis. A post-mortem morphological diagnosis of marked segmental non-suppurative myelitis and necrosis, and an aetiological diagnosis of toxoplasmosis were made. The clinical and pathological findings are supportive of CNS inflammation due to reactivation of latent tissue T gondii cysts.