Neuroaxonal dystrophy (NAD) in Papillons

Neuroaxonal dystrophy belongs to the group of rare inherited neurodegenerative diseases.  It has been described in various mammal species incl. humans, dogs, sheep, cattle, horses or cats and it occurs sporadically all over the world.

Clinical signs and the onset of the disease differ from species to species and among the individuals of the same species.  The first symptoms appear in puppies at approx. 3 months of age.  There can be observed problems with gait (it may develop partial or complete limb paralysis), loss of coordination, head tremor or intention tremor, inability to stand (astasia) and further neurological symptoms occur from the 6th month of age, such as blindness, strabismus, loss of reaction to threat, difficulty swallowing and progressive celebellar atrophy.

The characteristic pathologic features are heavy swellings of axons (spheroids) of the central and seldom even of the peripheral nervous system.

The disease is caused by mutation c.1579G>A in PLA2G6 gene that is involved in correct metabolism of phospholipids, the main components of cell membranes.

NAD also occurs in other dog breeds, but the mode of inheritance has not been clarified so far.   Breeds that are predisposed to NAD are: Rottweilers, Collies, German Shepherds, Papillons, Jack Russell Terriers, Spanish Water Dogs, Beagle-and-Schnautzer cross and Dachshund-cross .

NAD is a recessively inherited disease. The disease develops in dogs which inherit the mutated gene from each parent.  These dogs are designated as P/P (positive/positive). The carriers of the mutated gene are designated as N/P (negative/positive). The carriers inherited the mutated gene from one parent only and are without clinical signs. However, they pass the disease on to their offspring.  When mating two heterozygotes (N/P), there will be theoretically 25% of the offspring healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will be affected by NAD.  Mating one healthy dog (N/N) with a carrier of this mutation (N/P) will theoretically produce 50% carriers and 50% healthy offspring.  If a carrier (N/P) is mated with an affected dog (P/P), there will be theoretically 50% affected dogs and 50% carriers.

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References:

Tsuboi M, Watanabe M, Nibe K, Yoshimi N, Kato A, Sakaguchi M, et al. (2017) Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis. PLoS ONE 12(1): e0169002. doi:10.1371/journal.pone.0169002