Canis ISSN: 2398-2942

Neuroaxonal dystrophy

Synonym(s): NAD

Contributor(s): Kaspar Matiasek, Simon Platt, Laurent Garosi


  • Fatal, progressive neurodegenerative disorder.
  • Cerebellar-like clinical signs.
  • Hereditary or congenital in young Jack Russell terriers, Papillons, Chihuahuas, Collie Sheep dogs, Rottweilers, Boxers and German Shepherds.
  • No treatment.



  • Several reports have suggested an autosomal recessive inheritance.
  • In the Spanish Water dog Spanish Water dog the disease is caused by a mutation in the tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene which is involved in the autophagic pathways, axonal transport, and mitochondrial metabolism.
  • In the Papillon, the disease is caused by a mutation in the PLA2G6 gene. The precise mechanism of how dysfunction of PLA2G6 leads to axonal degeneration still remains unclear.


  • Current concepts of pathogenesis of both, inherited and physiologic, NADs in dogs suggest a disruption of the axonal transport system leading to a functional transsection of the nerve fiber.
  • The mechanisms by which spheroids develop in NAD are only partly known, but immunohistochemical methods have shown that NAD entails an accumulation of synapse-associated proteins, cytoskeletal proteins and other axonal markers, this suggesting an axonal transport deficit as the underlying cause of spheroid formation.


  • NAD is a monophasic and progressive disease.
  • The velocity of deterioration differs among the affected breeds. In Rottweilers the clinical picture gradually worsens over a time period up to several years; whereas in Jack Russell terriers, Papillons, Chihuahuas and Collie Sheep dogs a more rapid progression usually demands euthanasia within several weeks after presentation.


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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
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  • Tsuboi M, Watanabe M, Nibe K 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 PubMed.
  • Pintus D, Cancedda MG, Macciocu S et al (2016) Pathological findings in a Dachshund-cross dog with neuroaxonal dystrophy. Acta Vet Scand 58 (1), 37 PubMed.
  • Hahn K, Rohdin C, Jagannathan V et al (2015) TECPR2 associated neuroaxonal dystrophy in Spanish water dogs.  PLoS One 10 (11), e0141824 PubMed.
  • Fyfe J C, Al-Tamimi R A, Castellani R J et al (2010) Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia.  J Comp Neurol 518 (18), 3771-3784 PubMed.
  • Nibe K, Nakayama H, Uchida K (2009) Immunohistochemical features of dystrophic axons in Papillon dogs with neuroaxonal dystrophy. Vet Pathol 46 (3), 474-483 PubMed.
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Other sources of information

  • Braund KG (2003) Degenerative disorders of the central nervous system. In: Braund KG (ed)Clinical neurology in small animals localization, diagnosis and treatment. International Veterinary Information Service (, Ithaca, New York.
  • Lowe J S, Leigh P (2002) Disorders of movement and system degenerations. In: Graham D, Lantos P (eds)Greenfield's neuropathology. 7th edn, Arnold, London, pp 281-366.
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