Genetic basis of Congenital Myasthenic Syndrome - in cats is an autosomal recessive inherited neuromuscular disorder caused by a missense mutation in the COLQ gene. The COLQ gene encodes the collagen-like tail subunit of asymmetric acetylcholinesterase, which is crucial for proper signal transmission at the neuromuscular junction. Cats must inherit two copies of the pathogenic COLQ mutation (c.1190G>A, leading to a C397Y amino acid substitution in exon 15) to be affected. Carriers with one copy are unaffected but can pass the mutation to offspring. This mutation has been reported specifically in Devon Rex, Sphynx, and related breeds.
Pathophysiology - The COLQ mutation disrupts anchoring and clustering of acetylcholinesterase at the neuromuscular junction, leading to deficient termination of acetylcholine signaling. This results in prolonged muscle contraction and muscle weakness due to impaired neuromuscular transmission. Clinically, this manifests as progressive skeletal muscle weakness and fatigability starting as early as 3 months of age. Histopathology shows muscle fiber abnormalities without neurogenic changes. Electrophysiology may reveal reduced neuromuscular transmission efficiency.
Complications - Progressive muscle weakness and general fatigue, especially after exertion or stress. Peculiar gait with protruding shoulder blades and ventroflexion of head and neck. Megaesophagus causing difficulty swallowing and risk of aspiration. Muscle stiffness or spasticity in some cases. Reduced activity and exercise intolerance. Poor prognosis with progressive clinical signs impacting quality of life.
Why This Matters to Breeders and Vets - Breeders must use genetic testing to identify carriers and avoid breeding two carriers to prevent affected kittens (25% risk per litter). Responsible breeding can reduce prevalence. Veterinarians should consider CMS in young Devon Rex or Sphynx cats presenting with muscle weakness and neuromuscular signs. Genetic testing confirms diagnosis. Early diagnosis aids appropriate management and genetic counseling. Knowledge of this disorder informs breed health monitoring and guides veterinary care to improve affected cats’ welfare, although no cure currently exists.
Summary - Congenital Myasthenic Syndrome in cats is a rare autosomal recessive neuromuscular disease caused by a pathogenic missense mutation in the COLQ gene that disrupts acetylcholinesterase function at neuromuscular junctions. It predominantly affects Devon Rex and Sphynx cats, manifesting as progressive muscle weakness and fatigue starting in early life (around 3 months). Genetic testing is available and essential for diagnosis and breeding management. The disease is progressive and severely compromises quality of life.
