Early-Onset Progressive Polyneuropathy (NDRG1 gene, Alaskan Malamute)

Early-onset progressive polyneuropathy is characterized by dysfunction of the motor and sensory nerves, which can impair movement, breathing or other vital functions of the dog. One of the genes involved in the disease is NDRG1.


Clinical symptoms appear early, between 3 and 19 months of age. Early signs of the disease include exercise intolerance, as tremors or collapse may occur after exercise, abnormal gait movements and symmetrical hindlimb weakness. Other symptoms that may arise later include ataxia, vocal problems, severe muscle atrophy, inability to climb stairs or jump, hyporeflexia, difficulty swallowing and respiratory problems.

Disease Management

Today, there is no treatment for this condition. However, physical therapy and the creation of a safe and comfortable environment for the dog are two beneficial measures that help to improve the dog's quality of life.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

The function of the NDRG1 gene in dogs is not known exactly, but some studies claim that it plays a role in myelination, maturation and maintenance of the neuron. Likewise, in the study by Bruun et al. (2013) where a causative mutation of early-onset progressive polyneuropathy was identified in Alaskan Malamute, it was also observed that the NDRG1 gene is essential in axon development and maintenance. The variant identified as causative is a nonsynonymous substitution (c.293G>T) in exon 4, which results in the change of a glycine residue to a valine residue (p.G98V). These changes cause marked reduction (70%) of the expression of the protein encoded by NDRG1. Thus, affected dogs produce very low levels of protein, resulting in the phenotype described here, early-onset progressive polyneuropathy.

Most affected breeds

  • Alaskan Malamute


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