Neuroaxonal Dystrophy Papillon Type (NAD)
Neuroaxonal dystrophy Papillon type (NAD) is an inherited neurodegenerative disorder affecting the Papillon dog breed. It is a type of lipid storage disorder that primarily affects the nervous system. NAD has been diagnosed in various mammalian species, including humans, dogs, sheep, cattle, horses, cats, rabbits, rats and mice. Different NAD affected species share same pathological feature, which includes ”spheroids” in the central nervous system, but affected animals differ in time of symptoms’ onset and genetic mutation. In dogs, NAD has been recognized in several breeds, such as Rottweilers, Collie sheepdogs, Papillons, Jack Russell terriers, Spanish Water dogs etc. Among these breeds, NAD causative mutation has been so far identified only in Spanish Water dogs. Recent research has identified the NAD causative mutation also in Papillons, enabling performance of DNA test in order to recognize carrier and affected dogs.
Characteristics and Symptoms
Affected Papillons show symptoms of NAD from an early age, starting as early as 4 months of age. Symptoms include loss of coordination, such as wobbling gait and inability to stand upright (astasia). At 6 months of age neurological symptoms develope, which include blindness, loss of menace response, tremor and development of crossed eyes (strabismus). MRI examination shows cerebellar atrophy, with intact other regions of nervous system. With further disorder’s progression, dog shows difficulty while eating. Due to the low quality of life, affected dogs are usually euthanized at owner’s request.
Histopathological examination revealed a number of axonal spheroids throughout the central nervous system (CNS), including the thalamus, hippocampus, mesencephalon, cerebellar cortex, cerebellar nuclei, medulla oblongata, and dorsal horn of the spinal cord. The number of Purkinje cells in the cerebellum was moderately decreased. A few spheroids may be as well present in the optic nerve.
Neuroaxonal dystrophy Papillon type (NAD) is caused by a mutation in the PLA2G6 gene. NAD in Papillons is inherited in an autosomal recessive pattern. Healthy parents of affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Neuroaxonal Dystrophy PapillonType (NAD). At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
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