Genetic basis of Charcot-Marie-Tooth disease type 4B2 in canines - is identified primarily in the Miniature Schnauzer breed. It is caused by a mutation in the SBF2 (also known as MTMR13) gene—a specific splice donor variant (c.2363+1 G>T in exon 19)—leading to abnormal mRNA splicing and protein truncation. The disease is inherited in an autosomal recessive manner: only dogs with two copies of the mutated gene (P/P genotype) show clinical signs; carriers (P/N genotype) are asymptomatic. Population data suggest about 4% of Miniature Schnauzers are affected, while 28% are carriers and 68% are non-carriers.
Pathophysiology - CMT4B2 in dogs results in demyelinating polyneuropathy: the protective myelin sheath around peripheral nerves is damaged, leading to slowed nerve conduction. Pathology reveals "folded" myelin sheaths (tomacula) and segmental demyelination, visible on nerve histology. Affected dogs (typically <2 years old) develop symptoms like regurgitation due to megaesophagus, laryngeal paralysis with an aphonic bark, and sometimes muscle weakness with gait abnormalities. Electrophysiological tests often show markedly reduced motor and sensory nerve conduction velocities (~20m/s). Dogs may have progressive muscle atrophy, especially in the hind legs, and flexor reflex loss. Incontinence and pneumonia are occasional complications.
Complications - Gastrointestinal: Regurgitation from megaesophagus, which increases the risk of aspiration pneumonia—a potentially fatal complication. Respiratory: Laryngeal paralysis, causing voice changes (aphonic bark) and potential breathing difficulties. Neuromuscular: Weakness, atrophy, gait changes, and decreased reflexes, impacting mobility. Long-term: Disease course is often stable with symptomatic management, but aspiration pneumonia is a significant risk and common cause of death.
Why This Matters to Breeders and Vets - Breeders: Genetic testing is crucial to avoid breeding two carriers, which could result in affected puppies. With 28% of Miniature Schnauzers as carriers, untested breeding can perpetuate or increase disease prevalence. Vets: Early recognition and diagnosis (via clinical signs and genetic testing) help manage symptoms and improve quality of life. Progressive complications (especially pneumonia and swallowing issues) need careful monitoring. Vets should counsel breeders and owners about genetic risks and management.
