Leonberger Polyneuropathy (LPN1)

Leonberger dogs may suffer from a neuromuscular disease called Leonberger Polyneuropathy (LPN). This disease, in its classical presentation, sets in before three years of age. The dog suffers from slowly worsening exercise intolerance and may 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. Additionally, these dogs may have noisy breathing, a change in their bark, or even difficulty breathing due to involvement of the larynx and laryngeal folds in the throat. Eventually the disease may progress to the point where 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. It is important to note that older dogs can also display some or all of these signs and suffer from disease, although typically when dogs are affected at an older age, the disease is less severe. 

Research carried out at the University of Minnesota, the University of Bern, and the University of California San Diego, indicates that polyneuropathy is likely a group of several genetically distinct, but clinically similar diseases. We have mapped two major genetic risk loci and identified the causative mutation in one of these loci that we now term LPN1. Dogs being homozygous mutant (two copies of the mutation) for this mutation will typically develop neuropathy before they reach 3 years of age.  Dogs heterozygous for this mutation (one copy of the mutation) might also develop mild clinical signs late in life, but they will most likely not develop severe disease.  The identified LPN1 mutation appears to be responsible for approximately one third of the cases of polyneuropathy in Leonbergers. The other two thirds of cases are apparently caused by different genetic mutations.

We have also identified homozygous mutant Saint Bernards with a biopsy confirmed polyneuropathy and clinical signs consistent with the disease. This test can be used in the Saint Bernard breed to aid in the diagnosis of polyneuropathy and to identify carriers in the breeding population.