COLQ variant associated with Devon rex and Sphynx feline hereditary myopathy

Some Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS). A genome-wide association study and whole-genome sequencing suggested a causal variant for this entity was a c.1190G>A variant causing a cysteine to tyrosine substitution (p.Cys397Tyr) within the C-terminal domain of collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). Alpha-dystroglycan expression, which is associated with COLQ anchorage at the motor end-plate, has been shown to be deficient in affected cats. Eighteen affected cats were identified by genotyping, including cats from the original clinical descriptions in 1993 and subsequent publications. Eight Devon Rex and one Sphynx not associated with the study were identified as carriers, suggesting an allele frequency of ~2.0% in Devon Rex. Over 350 tested cats from other breeds did not have the variant. Characteristic clinical features and variant presence in all affected cats suggest a model for COLQ CMS. The association between the COLQ variant and this CMS affords clinicians the opportunity to confirm diagnosis via genetic testing and permits owners and breeders to identify carriers in the population. Moreover, accurate diagnosis increases available therapeutic options for affected cats based on an understanding of the pathophysiology and experience from human CMS associated with COLQ variants

Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts

BACKGROUND: In children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine. HYPOTHESIS/OBJECTIVES: Congenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype. ANIMALS: Using proper pedigree analysis and genetic evaluations, 20 related Oriental‐derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied. METHODS: Complete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats. RESULTS: Neurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type‐1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities

Subluxação atlantoaxial em 14 cães (2003-2008)

O objetivo deste trabalho foi realizar um estudo retrospectivo dos casos de subluxação atlantoaxial em cães, por meio de consulta dos registros neurológicos do Hospital Veterinário Universitário (HVU), entre os anos de 2003 e 2008. Foram identificados a raça, o sexo, a idade, a etiologia, os sinais neurológicos, a duração dos sinais clínicos, o tratamento empregado, a resposta ao tratamento, o tempo de recuperação, a recidiva e a relação entre a duração dos sinais clínicos e a recuperação pós-operatória. Foram feitos o diagnóstico de subluxação atlantoaxial em 14 cães, sendo as raças Poodle (35,7%), Pinscher (21,4%) e Yorkshire Terrier (21,4%) as mais acometidas e a maioria (92,8%) com idade inferior a 24 meses. A principal causa da instabilidade foi a agenesia do processo odontoide do áxis (71,4%) e os sinais clínicos variaram desde hiperestesia cervical até tetraparesia não ambulatória. O tratamento predominante foi o cirúrgico, que demonstrou ser eficaz com recuperação satisfatória em 90% dos casos e menor possibilidade de recidiva, quando comparado ao trata,mento clínico. O tempo de recuperação predominante foi de 30-60 dias após a cirurgia, não existindo relação deste com a duração dos sinais clínicos.<br>A retrospective study on atlantoaxial subluxation in dogs was done by reviewing the cases filed from 2003 to 2008 in the neurological records of the Veterinary Hospital of the Universidade Federal de Santa Maria, at Santa Maria, Rio Grande do Sul, Brazil. The following data were identified: Breed, sex, age, etiology, clinical signs, duration of clinical course, assessment of the therapy employed and its efficacy, response to treatment and relapse. Fourteen dogs were diagnosed as affected by atlantoaxial subluxation and the condition was more frequent in dogs under twenty-four month old years and of toy breeds, such as Poodle (35.7%), Pinscher (21.4%) and Yorkshire terrier (21.4%). The main cause found for the instability was agenesis of the odontoid process. Clinical signs ranged from cranial cervical pain to non-ambulatory tetraparesis. The predominant treatment employed was surgical which demonstrated to be efficacious in 90% of the cases with minor risks of relapse when compared with clinical treatment. The predominant time of recovery was 30-60 days after surgery. No correlation was found between the duration of clinical signs before surgery and the time of recovery