Genetic basis - Caused by a frameshift mutation in the CHRNE gene, which encodes the epsilon subunit of the acetylcholine receptor at the neuromuscular junction. The specific mutation is a 1 base pair insertion (c.636_637insC) in exon 7 of the CHRNE gene. This mutation leads to a premature stop codon, resulting in deficient acetylcholine receptor protein. The disease is inherited in an autosomal recessive manner, meaning affected dogs have two copies of the mutated gene.
Pathophysiology - Deficiency of acetylcholine receptors severely impairs neuromuscular transmission. This causes fatigable muscle weakness starting early in life—often at or soon after weaning. Reduced receptor availability leads to generalized skeletal muscle weakness and decreased spinal reflexes.
Clinical Signs - Muscle weakness worsening with exercise or excitement. Abnormal gait, difficulty standing or moving. Decreased muscle tone and reduced spinal reflexes. Onset usually by 2 to 4 weeks of age. Disease progression leads to significant mobility problems. Most affected puppies do not survive beyond 1 year without supportive care.
Diagnosis - Clinical signs and neurological exams consistent with neuromuscular junction disorder. Electromyography and response to anticholinesterase drugs confirm diagnosis. Genetic testing confirms CHRNE mutation presence.
Why This Matters to Breeders and Vets - Breeders: Genetic testing identifies carriers and prevents mating two carriers, thereby reducing affected puppies. Vets: Early diagnosis aids symptom management and guides client counseling about prognosis and care.