Test Detail
Neuroaxonal dystrophy (NAD) in the Papillon
Neurological · Dog
Neuroaxonal dystrophy (NAD) in the Papillon is an autosomal recessive neurodegenerative disease with axonal degeneration and spheroid formation in the central nervous system, caused by a missense variant in PLA2G6. It begins in young puppies with intention tremor and progresses to cerebellar ataxia, tetraplegia, blindness and deafness, with a fatal outcome within the first months.
Incidence
Described in the Papillon. Raj and Giger (2020): 17.5% heterozygotes among 660 Papillons from North America and Europe (allele frequency 0.092); later surveys of the breed placed the allele frequency at around 0.047.
Breeder management
- Genotype Papillon breeding dogs before breeding\n- Do not mate carrier × carrier (25% risk of affected offspring)\n- A carrier can be mated to a clear dog; test the offspring intended for breeding\n- Confirm with a genetic test every puppy with early neurological signs
Specialist notes
Histopathology shows multiple axonal spheroids disseminated throughout the central nervous system (cerebrum, hippocampus, thalamus, midbrain, cerebellum, brainstem and spinal cord), with peripheral nerves usually spared. The differential diagnosis includes other cerebellar ataxias and degenerative neuropathies; definitive confirmation is the PLA2G6 genetic test. There is no curative treatment.
References
1. Tsuboi 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:e0169002. PMID: 28107443
2. 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. PMID: 33292730
3. Nibe et al. (2007). Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs. J Vet Med Sci 69:1047-1052. PMID: 17984592
4. Lucot et al. (2018). A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs. G3 (Bethesda) 8:2773-2780. PMID: 29945969
5. Hahn et al. (2015). TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs. PLoS One 10:e0141824. PMID: 26555167
6. OMIA:002105-9615. Neuroaxonal dystrophy, PLA2G6-related in Canis lupus familiaris (dog).
2. 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. PMID: 33292730
3. Nibe et al. (2007). Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs. J Vet Med Sci 69:1047-1052. PMID: 17984592
4. Lucot et al. (2018). A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs. G3 (Bethesda) 8:2773-2780. PMID: 29945969
5. Hahn et al. (2015). TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs. PLoS One 10:e0141824. PMID: 26555167
6. OMIA:002105-9615. Neuroaxonal dystrophy, PLA2G6-related in Canis lupus familiaris (dog).