MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Increased teat wall thickness in response to machine milking.

Transiently increased teat wall thickness in response to machine milking has been documented by various methods, including ultrasound. However, correlative ultrasonography and histology to detect the origin of this phenomenon is lacking. The first goal of the present study was to evaluate and compare milking-related changes of the teat tissue in 2 breeds of dairy cows (11 Simmental and 3 Holstein) using B-mode ultrasonography. Additionally, the observed changes were compared with ultrasonographic findings in a Holstein cow with periparturient udder edema. Finally, corresponding histological sections of the Simmental teats were analyzed and compared with those from a lactating nonmilked Angus cow. We hypothesized that the mechanical load of both stretching by the vacuum during phases of open teat cup liner and compression by the closed liner during machine milking results in a transient congestion of blood vessels in the teat wall. The barrel of 1 front teat of each cow was scanned immediately before and after machine milking (system vacuum: 42 kPa; pulsation rate: 60 cycles/min; pulsation ratio: 65:35). Shortly after milking (33 ± 6 min), the Simmentals were slaughtered, and their scanned teat was immediately removed and processed for investigation by light microscopy. Ultrasonography after milking revealed anechoic tubular structures mainly in the inner half of the teat wall. Histological examination revealed these structures to be thick-walled veins. The left front and hind teats of the nonmilked lactating cow, collected and prepared identically to those from the Simmental cows, showed the same histological features. Ultrasonographic measurements showed that the diameter of these veins significantly increased after milking compared with matching images before milking. This effect was most pronounced in the Holstein cows. Similarly, these veins were very prominent in the periparturient cow. However, neither the milked cows, including the periparturient cow, nor the lactating nonmilked cow provided any evidence of edematous extravasation on ultrasonography or histology. These findings corroborated our hypothesis that the increase in size of thick-walled veins in the teat tissue is the main reason for the thickening of the teat walls in response to machine milking.

Feasibility, indications, and radiographically confirmed diagnoses of standing extremity cone beam computed tomography in the horse.

OBJECTIVE: To report on the feasibility, indications, and diagnostic yield of cone beam computed tomography (CBCT) of horses' extremities performed under standing sedation. STUDY DESIGN: Retrospective clinical case series. SAMPLE POPULATION: Fifty-nine CBCT examinations in 58 horses. METHODS: Examinations were categorized for indications for CBCT dependent on a suspicion, presence, or absence of a diagnosis prior to CBCT. The number of acquisitions per examination, total time for the examination, diagnostic score of each acquisition (diagnostic, diagnostic-compromised, nondiagnostic), and additional diagnostic information regarding preexisting diagnostic information were recorded. RESULTS: Three (median) acquisitions were performed per examination in a median study time of 14 minutes. In 24 of 33 cases with a suspected diagnosis, this diagnosis was confirmed or definitively refuted; in seven of 33 cases, the suspected diagnosis was refuted without a new diagnosis; and, in two of 33 cases, the suspected diagnosis could not be confirmed nor could a new diagnosis be made. In five of nine cases without a preexisting diagnosis, a diagnosis was established. In 16 cases with a diagnosis prior to CBCT, additional information was recorded, or a surgical plan was prepared. In 14 of 18 cases in which additional contrast techniques were used, additional information was gained. CONCLUSION: Standing CBCT of the horses' extremities is feasible and can produce diagnostic information in a timely fashion. CLINICAL SIGNIFICANCE: The results provide evidence of the practicality and diagnostic potential of standing CBCT of horses' extremities.

Analysis of blood degradation products and ferritin in the cerebrospinal fluid of dogs with acute thoracolumbar intervertebral disk extrusion, a prospective pilot study.

BACKGROUND: Hemorrhage in the spinal canal leads to further damage of the spinal cord influencing outcome in dogs with intervertebral disk (IVD) extrusion. The aim of the study was to evaluate blood degradation products and ferritin in the cerebrospinal fluid (CSF) of dogs with thoracolumbar IVD extrusion, and their association to clinical parameters and MRI findings. RESULTS: In the CSF of dogs with IVD extrusion, both net oxyhemoglobin absorption (NOA) and net bilirubin absorption (NBA) were significantly higher compared to the control groups of dogs with steroid responsive meningitis arteritis (SRMA) and idiopathic epilepsy (IE) (P < 0.001), but NOA compared to the idiopathic epilepsy group contaminated artificially with blood (IEc) was not (P = 0.890). Ferritin concentration was significantly higher in dogs with IVD extrusion compared to dogs with IE (P = 0.034), but not to dogs with SRMA (P = 0.526). There was no association between NOA, NBA or ferritin concentration and severity or duration of clinical signs. In dogs with a higher ferritin concentration the outcome was better (P = 0.018). In dogs with evidence of hemorrhage on MRI, NOA and NBA were significantly higher (P = 0.016, P = 0.009), but not ferritin (P = 0.0628). CONCLUSION AND CLINICAL IMPORTANCE: Quantification of blood degradation products and ferritin in the CSF of dogs to assess subarachnoidal hemorrhage is feasible; however, larger case numbers are needed to evaluate the relevance of NBA and ferritin as prognostic indicators.

Influence of body weight, age, and sex on cerebrospinal fluid peak flow velocity in dogs without neurological disorders.

BACKGROUND: Changes in the brain can affect the flow velocity of cerebrospinal fluid (CSF). In humans, the flow velocity of CSF is not only altered by disease but also by age and sex. Such influences are not known in dogs. HYPOTHESIS: Peak flow velocity of CSF in dogs is associated with body weight, age, and sex. ANIMALS: Peak flow velocity of CSF was measured in 32 client-owned dogs of different breeds, age, and sex. METHODS: Peak flow velocity of CSF was determined by phase-contrast magnetic resonance imaging (PC-MRI) at the mesencephalic aqueduct, foramen magnum (FM), and second cervical vertebral body (C2). Dogs were grouped according to body weight, age, and sex. Flow velocity of CSF was compared between groups using linear regression models. RESULTS: Dogs with body weight >20 kg had higher CSF peak velocity compared with dogs <10 kg within the ventral and dorsal subarachnoid space (SAS) at the FM (P = .02 and P = .01, respectively), as well as in the ventral and dorsal SAS at C2 (P = .005 and P = .005, respectively). Dogs ≤2 years of age had significantly higher CSF peak flow velocity at the ventral SAS of the FM (P = .05). Females had significantly lower CSF peak flow velocity within the ventral SAS of FM (P = .04). CONCLUSION: Body weight, age, and sex influence CSF peak flow velocity in dogs. These factors need to be considered in dogs when CSF flow is quantitatively assessed.

Spinal Neuronavigation for Lumbar Plate Fixation in Miniature Breed Dogs.

OBJECTIVE: The main aim of this pilot study was to assess the feasibility of spinal neuronavigation for plate fixation of lumbar vertebrae in miniature breed dogs using a surgical navigation system in combination with a custom-made reference array. STUDY DESIGN: This was an experimental cadaveric study in five miniature breed dogs. METHODS: A 4-hole locking plate with four 2.0-mm locking screws was placed on two adjacent lumbar vertebrae using a neuronavigation system consisting of a mobile cone beam computed tomography linked to a navigation system. The procedure was performed by a novice surgeon. The plate and screw positions were assessed for surgical safety using predefined criteria. Surgical accuracy was determined by the deviation of entry and exit points between pre- and postoperative images. RESULTS: A total of five plates and 20 screws were placed. In 85% (17/20), screws were placed appropriately. The median entry point deviation was 1.8 mm (range: 0.3-3.7) and the median exit point deviation was 1.6 mm (range: 0.6-5). CONCLUSION: Achievement of surgical accuracy in the placement of screws for fixation of lumbar vertebral plates in small breed dogs using neuronavigation with a custom-made reference array by a novice surgeon resulted in surgical safe plate placement in four of the five cadavers. Therefore, we judge the method as promising, however, further studies are necessary to allow the transfer of image-guided navigation for lumbar plate fixation into the clinic.

Isolation of Tumour-Derived Extracellular Vesicles From the Plasma of Dogs Affected by Intracranial Tumours Showing Heterologous and Cross-Species Tropism: A Pilot Study.

Canine and human brain tumours exhibit similar incidence rates and prognoses. Recent studies have demonstrated that extracellular vesicles derived from human patients (PDEVs) can be loaded with contrast agents and exhibit tumour tropism in murine models. We showed in a previous study that gadolinium-labelled EVs derived from canine gliomas (cPDEVs) can selectively targets murine glioblastoma cells in animal models. As a further step, we investigated the potential heterologous and cross-species tumour tropism of cPDEVs with brain tumours. With the perspective of imminent clinical application as both markers and drug delivery tools, we have successfully established the isolation protocol for cPDEVs and confirmed the aseptic conditions of the procedure and therefore the sterility of the isolated EVs. To assess the functionality of cPDEVs as drug delivery tool, they were loaded with indocyanine green (ICG) and injected into murine models of cancer for in vivo fluorescence biodistribution studies. Biodistribution analysis in mice revealed that ICG-loaded cPDEVs injected into murine models of subcutaneous tumours accumulated exclusively in the neoplastic tissue, even when evaluated 24 h post-injection, thus showing the cross-species and heterologous selective tumour tropism of the nanoparticles. With these tests, we have established a safe protocol for isolating and loading autologous cPDEVs with various markers, thereby paving the way for the clinical testing phase. These significant findings suggest the potential use of cPDEVs as a theranostic tool in the management of canine brain tumours, with promising implications for translational medicine applications in the future.

Grading of oligodendroglioma in dogs based on magnetic resonance imaging.

BACKGROUND: Oligodendroglioma (OG) accounts for 22% of primary brain tumors in dogs. Oligodendroglioma in dogs is graded as low-grade (II) or high-grade (III), based on the presence of microvascular proliferation and necrosis. OBJECTIVE: To investigate if magnetic resonance imaging (MRI) features differ between OG II and III in dogs. ANIMALS: Thirty-two dogs with histological diagnosis of intracranial OG and MRI. METHODS: Retrospective descriptive study. Histology was reviewed to grade OG according to the revised classification. Brain MRI results were reviewed following criteria including contrast enhancement (CE) pattern, presence of cystic structures, gradient-recalled-echo (GRE) signal voids, and necrosis based on signal intensity, as well as diffusion-weighted imaging characteristics. The MRI features were compared between OG II and III using Fisher's exact tests and logistic regression models. RESULTS: Histology identified 8 dogs with OG II (25%) and 24 with OG III (75%). All OG III showed moderate-to-marked CE including 18/24 (75%) with a ring pattern. These features were not seen in OG II. Heterogeneity, cystic structures, GRE signal voids, and necrosis were associated with OG III. No difference in diffusion characteristics was detected between OG II and III. CONCLUSION AND CLINICAL IMPORTANCE: Moderate-to-marked CE and ring pattern were present in dogs with OG III but not in OG II. The presence of cystic structures, GRE signal voids, and necrosis was strongly associated with OG III. Although the importance of brain tumor grading in dogs with regard to prognosis and treatment options remains unknown, the results indicate that MRI reflects the histological features used for grading OG in dogs.

Clinical and magnetic resonance imaging features of lymphoma involving the nervous system in cats.

BACKGROUND: Lymphoma is the most common spinal cord neoplasm and second most common intracranial tumor in cats, but description of specific magnetic resonance imaging (MRI) features is lacking. OBJECTIVE: Describe the clinical and MRI features of lymphoma affecting the central (CNS) or peripheral (PNS) nervous system or both in cats. ANIMALS: Thirty-one cats with confirmed cytological or histopathological diagnosis or both of lymphoma involving the CNS or PNS or both, and MRI findings of the lesions. METHODS: Multicenter retrospective descriptive study. Signalment and medical information were recorded. Magnetic resonance imaging findings were reviewed by 3 observers following a list of predefined criteria and consensus was sought. Frequency distributions of the different categorical data were reported. RESULTS: Median duration of clinical signs at time of presentation was 14 days (range, 1-90). Neurological examination was abnormal in 30/31 cats. On MRI, lesions affecting the CNS were diagnosed in 18/31 cats, lesions in both CNS and PNS in 12/31, and lesions in the PNS only in 1/31. Intracranial lesions were diagnosed in 22 cats (extra-axial, 7/22; intra-axial, 2/22; mixed, 13/22), and spinal lesions were diagnosed in 12 (6/12 involving the conus medullaris and lumbosacral plexuses). Infiltration of adjacent extra-neural tissue was present in 11/31 cases. Contrast enhancement was seen in all lesions, being marked in 25/30. Meningeal enhancement was present in all but 2 cases. Several distinct MRI patterns were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Nervous system lymphoma in cats has a wide range of MRI features, of which none is pathognomonic. However, together with clinical data and cerebrospinal fluid (CSF) analysis, MRI may provide a strong tentative antemortem diagnosis.

PCYT1A Missense Variant in Vizslas with Disproportionate Dwarfism.

Disproportionate dwarfism phenotypes represent a heterogeneous subset of skeletal dysplasias and have been described in many species including humans and dogs. In this study, we investigated Vizsla dogs that were affected by disproportionate dwarfism that we propose to designate as skeletal dysplasia 3 (SD3). The most striking skeletal changes comprised a marked shortening and deformation of the humerus and femur. An extended pedigree with six affected dogs suggested autosomal recessive inheritance. Combined linkage and homozygosity mapping localized a potential genetic defect to a ~4 Mb interval on chromosome 33. We sequenced the genome of an affected dog, and comparison with 926 control genomes revealed a single, private protein-changing variant in the critical interval, PCYT1A:XM_038583131.1:c.673T>C, predicted to cause an exchange of a highly conserved amino acid, XP_038439059.1:p.(Y225H). We observed perfect co-segregation of the genotypes with the phenotype in the studied family. When genotyping additional Vizslas, we encountered a single dog with disproportionate dwarfism that did not carry the mutant PCYT1A allele, which we hypothesize was due to heterogeneity. In the remaining 130 dogs, we observed perfect genotype-phenotype association, and none of the unaffected dogs were homozygous for the mutant PCYT1A allele. PCYT1A loss-of-function variants cause spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) in humans. The skeletal changes in Vizslas were comparable to human patients. So far, no ocular phenotype has been recognized in dwarf Vizslas. We propose the PCYT1A missense variant as a candidate causative variant for SD3. Our data facilitate genetic testing of Vizslas to prevent the unintentional breeding of further affected puppies.

Post-mortem Computed Tomographic Angiography in Equine Distal Forelimbs: A Feasibility Study.

In-depth understanding of pathophysiological processes occurring in the vasculature of the equine distal limb is of great importance to improve both diagnostic and therapeutic approaches to diseases. To gain further insights, a model allowing high-resolution 3D-visualization of the vasculature is necessary. This pilot study evaluated the feasibility of restoring vascular perfusion in frozen-thawed distal equine cadaver limbs without prior preparation using computer tomographic imaging (CT). Five frozen-thawed, radiographically normal forelimbs were perfused with a lipophilic contrast agent through the median artery and radial vein in three phases (arterial, venous, and arterial-venous combined (AVC) dynamic). For comparison, one additional limb was perfused with a hydrosoluble contrast agent. The CT-studies (16-slice MDCT, 140 kV, 200 mA, 2 mm slice thickness, 1 mm increment, pitch 0.688) were evaluated at 11 specified regions for visualization of the vasculature and presence of artifacts or anatomic variations. The protocol used in this study proved to be feasible and provided good visualization (93.1%) of vasculature with low rates of artifacts. During the different phases, vascular visualization was similar, but while filling defects decreased in the later phases, extravasation worsened in the 2 limbs where it was observed. Subjectively, the best quality of angiographic images was achieved during the AVC dynamic phase. Perfusion with hydrosoluble contrast resulted in significantly lower vascular visualization (74.0%) and higher artifact rates. This study shows that reperfusion of frozen-thawed equine distal limbs with a lipophilic contrast agent allows for high-quality 3D-visualization of the vasculature and may serve as a model for in situ vascular evaluation in the future.

Otitis media and interna with or without polyps in cats: association between meningeal enhancement on postcontrast MRI, cerebrospinal fluid abnormalities, and clinician treatment choice and outcome.

OBJECTIVES: The aim of this study was to evaluate the association between meningeal enhancement (MgE) and cerebrospinal fluid (CSF) analysis results, their individual association with bacteriology results from affected ear samples and whether these test results influenced clinicians' therapeutic choice in cats with otitis media and interna (OMI). METHODS: This was a multicentre retrospective study carried out over an 8-year period. Cats diagnosed with OMI, with or without a nasopharyngeal polyp, leading to peripheral vestibular signs were included. Only cats for which MRI with postcontrast T1-weighted sequences and CSF analyses available were included. Cats with intra-axial MRI lesions or empyema were excluded. RESULTS: Fifty-eight cats met the inclusion criteria. MgE was reported in 26/58 cases, of which nine had an abnormal CSF result (increased total nucleated cell count [TNCC] or total protein); 32/58 cases had no MgE, of which 10 showed abnormal CSF results. There was no association between bacteriology results (external ear canal or bulla) and MgE or abnormal CSF results. CSF abnormalities were statistically significantly more common in acute cases (n = 16/37) than in chronic cases (n = 3/21; Fischer's test P = 0.04). Prednisolone was prescribed in 10/16 cases with increased TNCC. Among the 42 cases with normal TNCC, 15 received prednisolone and 13 received non-steroidal anti-inflammatory drugs. Various antimicrobial drugs were prescribed in 53/58 cats. Duration of antimicrobial treatment was similar, regardless of positive bacterial culture (5.58 vs 4.22 weeks), abnormal CSF (5.83 vs 4.76 weeks) or MgE (5.33 vs 4.90 weeks). CONCLUSIONS AND RELEVANCE: No association was found between the CSF and MgE results. Furthermore, no association was found between MgE, CSF or bacteriology findings. In addition, abnormal CSF results might lead the clinician to treat with corticosteroids, but they did not have any impact on duration of antimicrobial treatment. CSF abnormalities were seen significantly less frequently in chronic cases. The outcome tended to be poorer when MgE was detected on MRI.

[Diagnostics in epilepsy - potential of magnetic resonance imaging]. / Diagnostik der Epilepsie ­ Möglichkeiten der Magnetresonanztomografie.

Epilepsy is a common neurologic disease frequently encountered by small animal practitioners. The disease comprises a multiplicity of clinical presentations and etiologies and often necessitates a comprehensive as well as cost-intensive diagnostic workup. This is mandatory in order to be able to diagnose or exclude a metabolic cause of the seizures and to distinguish between idiopathic and structural epilepsy. The examination by means of magnetic resonance imaging (MRI) represents a central component of the diagnostic workup, which in turn has essential effects on treatment and prognosis. In order to achieve standardized examination and comparable results, it is of utmost importance to use defined MRI protocols. Accordingly, communication and interaction between clinical institutions may be facilitated and as of yet undetected structural changes might be recorded in future MRI techniques. This review article sets particularly emphasis on the definition and classification of epilepsy as well as its diagnostic imaging procedures and refers to statistics and specialists' recommendations for the diagnostic workup in dogs.

Haematomyelia and myelomalacia following an inadvertent thoracic intraspinal injection in a cat.

CASE SUMMARY: A 4-month-old cat was presented with acute paraplegia after the referring veterinarian performed a subcutaneous injection (cefovecin and dexamethasone) in the caudodorsal thoracic area, during which the cat suddenly became uncooperative. A complete neurological examination performed 1 day after the injection revealed paraplegia without deep pain perception and reduced segmental spinal reflexes in the pelvic limbs. Findings were consistent with either an L4-S3 myelopathy or a T3-L3 myelopathy with subsequent spinal shock. MRI showed swelling of the spinal cord from T1 to L1 with heterogeneous T2-weighted intramedullary hyperintensity and no contrast enhancement. A centrally located intraspinal signal void was visible in T2*-weighted images. These changes were compatible with a suspected traumatic intraspinal injection. Despite intensive supportive care over 4 days, neurological status did not improve and the cat was euthanased. Gross pathology findings revealed severe intramedullary haemorrhage and myelomalacia in the T10-L1 spinal cord segments. Histopathology of the spinal cord after haematoxylin and eosin staining revealed a severe intramedullary space-occupying haemorrhage with focal malacia. A trajectory-like, optically empty cavity containing some eosinophilic droplets at the edges was detected. Although no further evidence of trauma was noted in the surrounding structures, the spinal cord changes were compatible with a perforating trauma. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of thoracic intraspinal injection causing myelomalacia defined by an ante-mortem MRI and confirmed post mortem by histopathology. The traumatic myelopathy appeared to be most compatible with an intraspinal injection causing vascular rupture.

Neuronal current imaging: An experimental method to investigate electrical currents in dogs with idiopathic epilepsy.

BACKGROUND: The diagnosis of idiopathic epilepsy (IE) in dogs is based on exclusion of other potential causes of seizures. Recently, a novel magnetic resonance imaging (MRI) sequence that utilizes a variant of the rotary saturation approach has been suggested to detect weak transient magnetic field oscillations generated by neuronal currents in humans with epilepsy. HYPOTHESIS/OBJECTIVES: Effects on the magnetic field evoked by intrinsic epileptic activity can be detected by MRI in the canine brain. As proof-of-concept, the novel MRI sequence to detect neuronal currents was applied in dogs. ANIMALS: Twelve dogs with IE and 5 control dogs without a history of epileptic seizures were examined. METHODS: Prospective case-control study as proof-of-concept. All dogs underwent a clinical neurological examination, scalp electroencephalography, cerebrospinal fluid analysis, and MRI. The MRI examination included a spin-locking (SL) experiment applying a low-power on-resonance radiofrequency pulse in a predefined frequency domain in the range of oscillations generated by the epileptogenic tissue. RESULTS: In 11 of 12 dogs with IE, rotary saturation effects were detected by the MRI sequence. Four of 5 control dogs did not show rotary saturation effects. One control dog with a diagnosis of neuronal ceroid lipofuscinosis had SL-related effects, but did not have epileptic seizures clinically. CONCLUSIONS AND CLINICAL IMPORTANCE: The proposed MRI method detected neuronal currents in dogs with epileptic seizures and represents a potential new line of research to investigate neuronal currents possibly related to IE in dogs.

Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs.

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs.