A 6-month-old, male, intact mixed breed dog was presented for a 3-month history of progressive generalized weakness. Neurologic examination revealed non-ambulatory tetraparesis, weakness of the head and neck, and decreased withdrawal reflexes in all limbs consistent with a generalized neuromuscular disorder. Electromyography and motor nerve conduction velocity were normal. Repetitive nerve stimulation showed a decremental response of the compound muscle action potential with improvement upon intravenous administration of edrophonium chloride. The serum acetylcholine receptor (AChR) antibody titer was within reference range. Cerebrospinal fluid analysis was unremarkable. A presumptive diagnosis of post-synaptic congenital myasthenic syndrome (CMS) was made. Treatment with pyridostigmine bromide was initiated with titrated increases in dosage resulting in an incomplete improvement in clinical signs. The dog was euthanized 2 months after initiation of treatment due to poor quality of life. Immunostaining for localization of antibodies against end-plate proteins in muscle biopsies was negative. Immunofluorescence staining for AChRs in external intercostal muscle biopsies showed absence of AChRs and biochemical quantitation showed a markedly decreased concentration of AChRs with no detectable AChR-bound autoantibody which confirmed the diagnosis of a CMS. Evaluation for the CHRNE mutation previously identified as the causative mutation of CMS in Jack Russell Terriers was performed and was negative. This is the first reported confirmed case of CMS in a mixed breed dog and provides a review of typical clinical and diagnostic findings as well as treatment considerations.Keywords: congenital myasthenic syndrome, myasthenia gravis, dog, pyridostigmine bromide, mixed breed, CHRNE Case pReseNtatIoNA 6-month-old, male, intact mixed breed dog [6.54 kg (14.4 lb)] was referred with a 3-month history of progressive generalized weakness. The dog was adopted at approximately 3 months of age after having been found as a stray. At the time of adoption, the dog was perceived to be normal. About 1 week later, it was noted that the dog developed an abnormal, stiff gait after playing and would sometimes fall over. The dog was also having difficulty posturing to defecate. Despite empirical treatment with clindamycin (12.3 mg/kg, PO, BID) and steroids (unknown type or dose), the dog displayed progressive episodes of weakness and falling following activity that eventually progressed to non-ambulatory tetraparesis over the next several months. On presentation, physical examination revealed grade 3/6 left and right apical systolic murmurs. Echocardiogram revealed mitral valve dysplasia causing systolic anterior motion of the mitral valve with severe dynamic left ventricular outflow tract obstruction and mild mitral regurgitation. In addition, there was a mild dynamic right ventricular outflow tract obstruction. Atenolol (1 mg/kg, PO, BID) was initiated. On neurologic examination, the dog was non-ambulatory tetraparetic (lower motor neuron qu...