Neuroaxonal dystrophy (NAD) is an inherited neurodegenerative disease described in the Spanish Water Dog. It is characterized by the formation of axonal spheroids (accumulation of autophagosomes) in the grey matter of the hemispheres, cerebellum, brainstem and spinal sensory pathways, with progressive degeneration and neurological signs. It is a spontaneous model of human hereditary spastic paraparesis associated with TECPR2.

Exclusive to the Spanish Water Dog. Carrier frequency in the population has not been published; population data are limited.

- Progressive incoordination (ataxia)\n- Loss of proprioception (limbs in abnormal position)\n- Generalized muscle weakness\n- Ataxic gait (exaggerated steps, stumbling)\n- Tremors\n- Difficulty walking on slippery surfaces\n- Slow and inexorable progression

Molecularly described by Hahn and colleagues (2015), who by SNP genotyping and whole-genome resequencing identified a missense variant in TECPR2 (c.4009C>T; p.Arg1337Trp) on chromosome 8, with homozygosity in affected dogs. The TECPR2 protein is involved in autophagy and its dysfunction causes the accumulation of autophagic material characteristic of the disease.

- Genotype the breeders\n- Do not cross carrier × carrier: 25 % affected homozygotes\n- A carrier may be crossed with a clear dog; test the offspring intended for breeding\n- Do not breed affected animals\n- Progressively replace carriers with clear descendants without narrowing the gene pool

The differential diagnosis includes other hereditary neuropathies, demyelinating diseases and idiopathic neuropathies. The TECPR2 genetic test is specific. There is no curative treatment; management is supportive (physiotherapy, environmental control). Progression is slow but inexorable.

1. Hahn K, et al. TECPR2 associated neuroaxonal dystrophy in Spanish Water Dogs. PLoS One. 2015;10(11):e0141824. PMID: 26555167
2. Cocostîrc V, et al. An overview of canine inherited neurological disorders with known causal variants. Animals (Basel). 2023;13(22):3568. PMID: 38003185