Neuroaxonal Dystrophy, NAD (Papillon type)

 

Gene: PLA2G6

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, PLA2G6 gene; c.1579 G>A, p.(T527A), exon10

Medical system: Neurologic

Breeds: Papillon / Continental Toy Spaniel, Phalène

Age of onset of symptoms: Two to three months

Neuronaxonal Dystrophy (NAD) is a neurodegenerative genetic disease seen in the Papillon breed of dogs.  Lipid metabolism and storage is altered, and the nervous system is particularly affected.  Swelling of the axons is seen throughout the central nervous system, and atrophy of the cerebellum occurs.  Clinically, puppies as young as 2-3 months are presented with wobbly gaits, intention tremors and weakness of voluntary movements.  By six months, neurological symptoms progress and can include difficulty eating, inability to stand or walk, and blindness.  There is no treatment, and affected dogs are usually euthanized for humanitarian reasons.

Note that Neuroaxonal Dystrophies (NADs) of differing severities and age of onset are seen in different breeds and are caused by mutations in different genes.  Here is a summary:

NAD, Giant Schnauzer type.  A severe disease that is lethal at birth.  MFN2 gene, OMIA [2153].

NAD, Papillon type: A progressive neurological disease with onset of symptoms by 3-4 months and death by 7-8 months.  PLA2G6 gene, OMIA [2105]

NAD, Rottweiler type.  A slowly progressive degenerative disease with a young adult onset usually resulting in ethical euthanasia.  VPS11 gene, OMIA [2152].

NAD, Spanish Water Dog type. A progressive degenerative disease with an onset of 6-11 months and ethical euthanasia by 2 years. TECPR2 gene, OMIA [1975]

 

References:

OMIA link: [2105-9615]

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]

Stee K, Van Poucke M, Lowrie M, et al. (2023) Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med. [pubmed/37341581]

Raj K, Giger U. (2020) Initial survey of PLA2G6 missense variant causing neuroaxonal dystrophy in Papillon dogs in North America and Europe. Canine Med Genet 7:17. [pubmed/33292730]

Tsuboi M, Watanabe M, Nibe K, et al. (2017) Identification of the PLA2G6 c.1579 G>A missense mutation in papillon dog neuroaxonal dystrophy using whole exome sequencing analysis. PLOS One 12(1):e0169002. [pubmed/28107443]