About the condition
Saint Bernard dogs may suffer from neuromuscular diseases collectively termed Laryngeal Paralysis and Polyneuropathy. Affected dogs may have noisy breathing, a change in their bark, and difficulty breathing due to involvement of the larynx and laryngeal folds in the throat. Additionally, they may suffer from slowly worsening exercise intolerance and develop gait abnormalities, such as an exaggerated hitched step, especially in the hind limbs. There is often wasting of the hind limb muscles as well. Eventually the disease may progress to the point where surgical intervention for laryngeal paralysis may be required and the dog cannot support its own weight. Biopsies of nerve from affected dogs show degradation of the nerve fibers and loss of myelin, the insulating material that normally helps speed messages along nerves. Muscle biopsies show atrophy resulting from nerve loss.
Research carried out at the University of Minnesota, the University of Bern, and the University of California, San Diego - Comparative Neuromuscular Laboratory indicates that laryngeal paralysis and polyneuropathy within the Saint Bernard breed is a group of several genetically distinct, but clinically similar diseases. We have mapped two major genetic risk loci: Leonberger Polyneuropathy type 1 (LPN1) (originally identified in Leonberger dogs) and Laryngeal Paralysis-Polyneuropathy Type 3 (LPPN3).
LPN1 - ARHGEF10
LPN1 is a polyneuropathy resulting from a 10 base pair deletion within the gene ARHGEF10; dogs homozygous (LPN1-D/D) for the LPN1 mutation typically develop clinical signs of disease before they reach 3 years of age.
- At present, LPN1-D/D dogs represent ~20% of all diagnosed cases of Saint Bernard laryngeal paralysis and polyneuropathy.
- Population testing of >350 Saint Bernards indicates that the carrier rate of this mutation is ~2%
LPPN3 - CNTNAP1
The LPPN3 mutation is inherited in an autosomal recessive manner meaning that two copies of the mutation are required to show signs of disease (LPPN3-D/D). LPPN3 affected Leonberger dogs typically develop severe laryngeal paralysis at a young age (average onset 2 years), with most affected dogs requiring laryngeal tieback surgery. Additional clinical signs, which were noted variably among the dogs, included difficulty swallowing, changes in barking frequency and quality, high-stepping and uncoordinated gait, stumbling and tripping, exercise intolerance, and muscle atrophy. Like many neurological diseases, there is no effective treatment for LPN. Since in most cases the dog is not in pain but is strongly restricted in its quality of life, especially due to the frequent loss of normal function of the larynx, owners are encouraged to ask a veterinarian for advice.
- This mutation explains ~40% of young onset laryngeal paralysis-polyneuropathy within the Saint Bernard.
- Population testing of >300 Saint Berndards indicates that the carrier rate is ~20%.
The tests for LPN1 and LPPN3 do not account for all confirmed or suspected cases of laryngeal paralysis and polyneuropathy in the Saint Bernard breed. Until additional DNA-based test(s) are developed, the only way to confirm a suspected diagnosis of laryngeal paralysis is via laryngoscopy and/or nerve conduction study; polyneuropathy is diagnosed via a nerve and muscle biopsy.
Dogs showing clinical signs of laryngeal paralysis or polyneuropathy may qualify for free LPN1 and LPPN3 testing. Special forms and instructions, as well as pre-approval, are required for free testing. Please e-mail [email protected] to see if your dog may be eligible.
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- A CNTNAP1 Missense Variant Is Associated with Canine Laryngeal Paralysis and Polyneuropathy
Letko A, Minor KM, Friedenberg SG, et al. (2020)
Genes 2020, 11, 1426. doi:10.3390/genes11121426
- An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.
Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, Bley T, et al. (2014)
PLoS Genet 10(10): e1004635. doi:10.1371/journal.pgen.1004635