Congenital neural tube defect of the Weimaraner, described in the literature as "spinal dysraphism" and the canine equivalent of human spinal dysraphisms and spina bifida. It is caused by defective closure of the neural tube during embryonic development and mainly affects the vertebral canal and the spinal cord. Puppies are already born with the alteration and present a neurological deficit of the hindlimbs that does not progress with age. It is inherited in an autosomal recessive manner and is associated with a mutation in the homeobox gene NKX2-8.

Affected breed: Weimaraner. Sporadic, possibly non-hereditary forms have been described in other breeds. No reliable carrier frequency has been published for NKX2-8; the figure of ~1.4% that circulates is not supported by the original source (Safra et al., 2013) or by OMIA.

- "Bunny hopping" gait of the hindlimbs\n- Weakness and lack of coordination of the hindquarters, with normal forequarters\n- Difficulty in initiating gait in puppies\n- Defective vertebral canal from birth\n- Non-progressive and non-painful course\n- Rarely, bunny hopping in the forequarters

Spinal dysraphism of the Weimaraner was described and maintained in experimental colonies long before its molecular basis was known; test crosses confirmed its recessive hereditary nature. In 2013, Safra and co-workers carried out a genome-wide association study with only four affected dogs and 96 controls, and mapped the disease to a 1.5 Mb region of chromosome 8 containing 18 genes. On sequencing the most plausible candidate, the homeobox gene NKX2-8, they identified a frameshift mutation (G→AA) in exon 2 that predicts a truncated protein. The same work found rare NKX2-8 variants over-represented in human patients with spina bifida, which confirms the Weimaraner as a natural model of neural tube defects.

- Test breeding animals with the NKX2-8 test before mating\n- Do not cross two carriers: 25% risk of affected homozygotes\n- A carrier can be crossed with a clear animal; offspring intended for breeding must be tested\n- Carriers (N/SD) are completely asymptomatic and can be crossed with clear animals to maintain genetic diversity\n- Exclude affected homozygous animals from breeding

Differential diagnosis with other causes of non-progressive ataxia/paraparesis in the puppy (Chiari malformation, syringomyelia, myelodysplasia) and with fibrocartilaginous embolism. The "bunny hopping" phenotype is highly suggestive but not pathognomonic. MRI and the genetic test confirm. As it is non-progressive and non-painful, the functional prognosis is reasonable, but the animals should not breed.

1. Safra N et al. (2013). Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans. PLoS Genet 9(7):e1003646. PMID: 23874236
2. OMIA:000938-9615. Spinal dysraphism in Canis lupus familiaris (dog).