Neuroaxonal dystrophy in Dogs (Canis) | Vetlexicon
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Neuroaxonal dystrophy

ISSN 2398-2942

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Synonym(s): NAD


  • 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.

Presenting signs

  • The term neuroaxonal dystrophy (NAD) refers to a group of neurodegenerative disorders of both CNS and PNS (the latter not well recognized in veterinary medicine) which are characterized histopathologically by swelling of preterminal axon segments and enlarged presynaptic buttons.
  • According to concomitant pathology, NAD can be classified as an idiopathic disease (primary) or as a symptom of another neurological disorder (reactive/secondary).
  • NAD-like alterations are observed regularly in aged animals and people, and this condition is called physiological NAD.
  • Causes of pathological NAD can be either inherited or acquired. Inherited NADs are supposed to follow an autosomal recessive trait. Etiology of the acquired form comprise endocrine disturbance, malnutrition and intoxication.
  • NADs have been observed throughout mammalian species including humans, dogs, cats, sheep, horses, rabbits, raccoons, mice and rats.
  • The following text is dedicated to inherited NADs in dogs.
  • Affected dogs usually develop a progressive abnormal gait during the first year of life with a sudden (Chihuahua) or insidious (other breeds) onset. Later manifestations are seen in Rottweilers (1-2 years) and German Shepherds (15 months).
  • The clinical picture is dominated by cerebellar-like signs including ataxia, intention-tremor, hypermetria, swaying and wide-based limb positioning.
  • According to case reports from Australia, Rottweiler puppies with NAD-plus pathology, where NAD is just one component of the disease complex, might develop life-threatening inspiratory insufficiency following laryngeal paralysis Larynx: paralysis.

Geographic incidence

  • Any geographic differences are based on local breeding preferences.

Age predisposition

  • Canine NADs resemble the juvenile (Rottweilers, German shepherds) and infantile (other breeds) human subtypes.
  • Animals usually become symptomatic within first year of life. Most reports demonstrate an onset of clinical signs before 4 months of age. In Boxers clinical signs might develop as late as 7 months of age, and German shepherds and Rottweilers most commonly are affected as young adults between 1 and 2 years. Alternatively, in the latter, symptoms may be subtle and slowly progressive, thereby, resulting in a delayed presentation to the clinician.

Breed/Species predisposition



  • 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.
  • Degl’Innocenti S, Asiag N, Zeira O et al (2017) Neuroaxonal dystrophy and cavitating leukocencephalopathy of Chihuahua dogs. Vet Pathol 54 (5), 832-837 PubMed.
  • 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.
  • Nibe K, Kita C, Morozumi M et al (2007) Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs. J Vet Med Sci 69 (10), 1047-1052 PubMed.
  • Diaz V J, Dunque C, Geisel R (2007) Neuroaxonal dystrophy in dogs: case report in 2 litters of Papillon puppies. J Vet Intern Med 21 (3), 531-534 PubMed.
  • Tamura S, Tamura Y, Uchida K (2007) Magnetic resonance imaging findings in neuroaxonal dystrophy in a papillon puppy. J Small Anim Pract 48 (8), 458-461 PubMed.
  • Sisó S, Ferrer I, Pumarola M (2001) Juvenile neuroaxonal dystrophy in a Rottweiler: accumulation of synaptic proteins in dystrophic axons. Acta Neuropathol 102 (5), 501-504 PubMed.
  • Bennett P F, Clarke R E (1997) Laryngeal paralysis in a rottweiler with neuroaxonal dystrophy. Aust Vet J  75 (11), 784-786 PubMed.
  • Boersma A, Zonnevylle H, Sanchez M  A et al (1995) Progressive ataxia in a Rottweiler dog. Vet Q 17 (3), 108-109 PubMed.
  • Franklin R J, Jefferey N D, Ramsey I K (1995) Neuroaxonal dystrophy in a litter of papillon pups. J Small Anim Pract 36 (10), 441-444 PubMed.
  • Sacre B J, Cummings J F, De Lahunta A (1993) Neuroaxonal dystrophy in a Jack Russell terrier pup resembling human infantile neuroaxonal dystrophy. Cornell Vet 83 (2), 133-142 PubMed.
  • Chrisman C L (1992) Neurological diseases of rottweilers: neuroaxonal dystrophy and leukoencephalopathy. J Small Anim Pract 33 (10), 500-504 Wiley Online Library.
  • Evans M G, Mullaney T P, Lowrie C T (1988) Neuroaxonal dystrophy in a rottweiler pup. J Am Vet Med Assoc 192 (11), 1560-1562 PubMed.
  • Blakemore W F, Palmer A C (1985) Nervous disease in the chihuahua characterised by axonal swellings. Vet Rec 117 (19), 498-499 PubMed.
  • Chrisman C L, Cork L C, Gamble D A (1984) Neuroaxonal dystrophy of Rottweiler dogs. J Am Vet Med Assoc 184 (4), 464-467 PubMed.
  • Cork L C, Troncoso J C, Price D L et al (1983) Canine neuroaxonal dystrophy. J Neuropathol Exp Neurol 42 (3), 286-296 PubMed.
  • Clark R G, Hartley W J, Burgess G S et al (1982) Suspected inherited cerebellar neuroaxonal dystrophy in collie sheep dogs. N Z Vet J 30 (7), 102-103 PubMed.

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.
  • Ackerman L (1999) The genetic condition: a guide to health problems in purebred dogs. AAHA Press, Lakewood, Colorado, pp 140-141.
  • Summers B A, Cummings J F, De Lahunta A (1995) Veterinary neuropathology. Mosby, St Louis, pp 315-317.