Leonberger Polyneuropathy 2 (LPN2)
Leonberger Polyneuropathy 2 (LPN2) is a form of neuropathy affecting this dog breed. It differs from other form of polyneuropathy affecting Leonbergers by a causative mutation. Polyneuropathy is a term used for simultaneous malfunction of many peripheral nerves throughout body and in literally translation it means “many abnormalities of the nervous system”. Other dog breeds affected by PN are Greyhounds, Alaskan Malamute, Black Russian Terriers, Rottweilers, and Alaskan Husky Dogs. Polyneuropathy observed in Leonbergers shows similar clinical symptoms to Charcot-Marie-Tooth (CMT) in humans. Charcot-Marie-Tooth (CMT) is a genetically heterogeneous group of neuropathies that cause damage of peripheral nerves. CMT is the most common inherited disorder of peripheral nerves in humans.
Affected Leonbergers show abnormal motor signs, such as weakness, hypotonia and muscle atrophy due to denervation. Other symptoms include laryngeal paralysis, a change in the bark, inspiratory stridor, and dyspnea.
The age on LPN onset is variable, from less than 1 year of age to 11 years of age. Dogs affected with an early onset of the disorder usually develop more severe symptoms and stages of the disorder.
Since Leonberger Polyneuropathy (LPN2) is a progressive disorder, owners in its beginning stages may not even notice the first symptoms, such as unbalanced walk. It is common that veterinarians are not able to recognize the disorder before the already progressed stages.
Leonberger Polyneuropathy (LPN2) is caused by a deletion mutation in the GJA9 gene. This gene encodes for gap junction protein alpha 9, which is a type of connexin. It is involved in the formation of gap junctions, connections between cells that directly connect the cytoplasms of contacting cells.
LPN2 is inherited in a dominant inheritance pattern with incomplete penetrance.
Other form of polyneuropathy has been also recognized in Leonberger dogs, known as LPN, which is caused by a different mutation, in a different gene.
Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE, et al. (2014) An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs. PLoS Genet 10(10): e1004635. doi:10.1371/journal.pgen.1004635