Polyneuropathy, demyelinating 

Gene: SBF2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution (splicing erreur), SBF2 gene; c.2363+1 G>T, p.G775V fs STOP 5)

Medical system: Neurological

Breeds: Schnauzer - Miniature

Age of onset of symptoms: Between 4 and 18 months, with a median age of 11 months.

Demyelinating polyneuropathy is a genetic disorder seen in Miniature Schnauzers where there is destruction or incorrect apposition of the myelin sheath around axons within the peripheral nervous system.  The myelin sheath is a layer of fat that covers nerve fibers in certain parts of the body, helping to speed up the transmission of nerve signals. The most common clinical signs of this disease include swelling of the esophagus (megaesophagus), leading to chronic regurgitation, and paralysis of the larynx, causing breathing difficulties on inspiration or barking without sound. The condition is stable and the prognosis is reasonable if feeding measures are taken to prevent aspiration pneumonia, which is the most serious potential problem.  DNA tests are now available such that elimination both the mutation and the disease from the breed is feasible.

References:

OMIA link: [2284-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Farré Mariné A, Granger N, Bertolani C, et al. (2020) Long-term outcome of Miniature Schnauzers with genetically confirmed demyelinating polyneuropathy: 12 cases. J Vet Intern Med 34:2005-11.  [pubmed/3273]

Granger N, Luján Feliu-Pascual A, Spicer C, et al. (2019) Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicing <i>SBF2 (MTMR13)</i> genetic variant: a new spontaneous clinical model. PeerJ 7:e7983.  [pubmed/31772832]

Vanhaesebrouck AE, Couturier J, Cauzinille L, et al. (2008) Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs. J Neurol Sci 275:100-5.  [pubmed/18809183]

Contributed by:  Andrew Bouthillier-Martineau and Fabien Castiello, class of 2027, Veterinary Medicine Faculty, University of Montreal.  (Translation: DWS).