Hereditary demyelinating peripheral neuropathy of the Miniature Schnauzer, the canine equivalent of human Charcot-Marie-Tooth type 4B2. It presents with motor and sensory demyelination, abnormally folded myelin and characteristic signs of lower cranial nerve dysfunction (regurgitation due to megaesophagus and aphonic bark), with or without apparent neuromuscular weakness. It is a spontaneous model of human CMT4B2.

Breed in which it has been described: Miniature Schnauzer. In a screen of 802 genomes from 162 breeds/mixed breeds/wolves, 2 heterozygous Miniature Schnauzers and 1 mutant homozygote were found; the rest were clear. There are no reliable frequency figures in the general breeding population (limited data).

- Regurgitation due to megaesophagus (11/12 cases)
- Aphonic bark (11/12 cases)
- Distal muscle weakness and atrophy (may be inconspicuous despite electrodiagnostic signs)
- Demyelinating neuropathy with focally folded myelin on nerve biopsy
- Onset between 3 and 18 months; presentation between 4 and 96 months
- Course often stable in the long term; risk of aspiration pneumonia

In 2008, a demyelinating neuropathy with focally folded myelin was described in a family of Miniature Schnauzers, compatible with human CMT and with autosomal recessive inheritance suspected by pedigree analysis. In 2019, a genome-wide association study and sequencing identified in SBF2 (MTMR13) a splice donor site variant (c.2363+1G>T) that induces a cryptic site and produces protein truncation; cosegregation with the disease was demonstrated. Subsequent studies confirmed the diagnostic value of the test and described the long-term clinical course.

- In the event of a confirmed case, do not repeat the parental mating (both parents are obligate carriers)
- Genotype breeding animals with the SBF2-specific molecular test before breeding
- Do not breed two carriers together: 25 % risk of affected homozygotes
- A carrier may be bred to a clear animal; the offspring intended for breeding must be tested
- Withdraw affected animals from breeding
- Inform the buyer of the genetic status and monitor aspiration pneumonia in affected dogs

Differential diagnosis with other polyneuropathies (diabetic neuropathy, senile neuropathy), myopathies and radiculopathies. Electromyography and nerve conduction velocity guide the diagnosis; nerve biopsy confirms demyelination with folded myelin. The clinical key in this breed is the combination of regurgitation with megaesophagus and aphonic bark. The molecular basis is well characterized and a direct genetic test is available.

1. Granger N, Luján Feliu-Pascual A, Spicer C, et al. Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicing SBF2 (MTMR13) genetic variant: a new spontaneous clinical model. PeerJ. 2019;7:e7983. PMID: 31772832
2. Farré Mariné A, Granger N, Bertolani C, et al. Long-term outcome of Miniature Schnauzers with genetically confirmed demyelinating polyneuropathy: 12 cases. J Vet Intern Med. 2020;34(5):2005-2011. PMID: 32738000
3. Vanhaesebrouck AE, et al. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs. J Neurol Sci. 2008;275(1-2):100-105. PMID: 18809183