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Canine Mendelian disease record

Neuroaxonal Dystrophy (Discovered in the Papillon; PLA2G6-related; NAD)

Neuroaxonal Dystrophy (Discovered in the Papillon; PLA2G6-related; NAD). Autosomal recessive. Observed in 1 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,599 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:002105-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human autosomal recessive Parkinson disease 14

This is the canine counterpart of autosomal recessive Parkinson disease 14 in people. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: A rare neurodegenerative disease usually presenting before the age of 30 and which is characterized by dystonia, L-dopa-responsive parkinsonism, pyramidal signs and rapid cognitive decline.

In humans it is also called: PARK14, autosomal recessive Parkinson disease type 14, dystonia-parkinsonism, Paisan-Ruiz type, Parkinson disease 14, autosomal recessive, PLA2G6 hereditary late onset Parkinson disease.

MONDO:0013060 OMIM 256600OMIM 610217

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

Neuroaxonal dystrophy in Papillon dogs was fist reported in 1995 in England [Franklin et al., 19851], and has since been reported in several other countries. Tsuboi et al. (2017) identified the likely causal variant.

Clinical features

Tsuboi et al. (2017) investigated three affected Papillon dogs: "The affected dogs initially developed intention tremor and hypermetria at a very young age, and the symptoms gradually progressed to cerebellar ataxia, tetraplegia, blindness, and deafness." Onset of disease was between 13-16 weeks of age and death occurred between 7 to 8 month of age.

Molecular genetics

Tsuboi et al. (2017): PLA2G6 c.1579G>A; p.T526A

Pathology

Tsuboi et al. (2017) investigated three affected Papillon dogs: "Histopathologically, multiple spheroid formation is observed throughout the central nervous system, including the cerebrum, hippocampus, thalamus, mesencephalon, cerebellum, pons, medulla oblongata, and dorsal horn of the spinal cord, while the peripheral nerves are generally unaffected."

Prevalence

Raj and Giger (2020): "Archived samples from Papillons clinically diagnosed with NAD prior to 2015 as well as samples obtained from 660 Papillons from North America and Europe between 2015 and 2017 were screened for the presence of this PLA2G6 gene variant (XM_022424454.1:c.1579G > A) ... .17.5% of the 660 tested Papillons were heterozygotes, resulting in a variant allele frequency of 0.092 in this initial survey. Since then, screening for NAD in Papillons by at least 10 other laboratories and data from the Health Committee of Papillon Club of America gathered between 2017 and 2019 reveal a variant allele frequency of 0.047."

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 256600 Disease · OMIM 610217 Disease · OMIM 612953 Gene · OMIM 603604

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:002105-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 8.

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Neuroaxonal Dystrophy (Discovered in the Papillon; PLA2G6-related; NAD) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Neuroaxonal Dystrophy (Discovered in the Papillon; PLA2G6-related; NAD) looks like in your dog's breed.
Carrier frequency by breed

Top 1 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%
Papillon0.25% · n 197
n = 197 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Neuroaxonal Dystrophy (Discovered in the Papillon; PLA2G6-related; NAD) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Papillon 0.25% 197

265 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:002105-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:002105-9615 · Donner et al. 2023