Neonatal encephalopathy with seizures, autosomal recessive, of the Standard Poodle. Affected puppies are small and weak at birth, suckle poorly, and if they survive the first week they develop ataxia, generalised tremor and severe tonic-clonic seizures between 4 and 6 weeks, refractory to treatment, with death or euthanasia before 7 weeks. It is associated with a missense mutation in ATF2.

Affected breed: Standard Poodle. The variant is widespread in the breed according to the initial characterisation studies; later population screenings provide carrier figures that should be consulted in the specific source. Breeds developed on a Standard poodle genetic base are also at risk.

- Small and weak puppies at birth\n- Failure to suckle and to develop in the first week\n- From ~3 weeks: ataxia, generalised tremor, wide-based stance with extensor hypertonia and axial weakness\n- Refractory generalised tonic-clonic seizures between 4 and 6 weeks\n- Depressed mental state, with no interaction with the mother or the litter\n- Death or euthanasia before 7 weeks

NEWS was recognised in 1997 in a Standard poodle litter and characterised as an autosomal recessive disease based on 18 affected puppies in the USA. In 2008, Chen and colleagues mapped the locus to a 2.87 Mb interval on CFA36 containing the canine orthologue of ATF2, and by sequencing the coding exons identified a c.152T>G transversion predicting the p.Met51Arg substitution, located in the hydrophobic docking site for MAP kinases that activate ATF-2. The variant co-segregated perfectly with the phenotype in 20 affecteds and 58 relatives. Later MRI and neuropathology studies extended the phenotype with cerebellar dysplasia and neuronal migration abnormalities.

- Test breeding animals with the ATF2 test before mating (highly recommended test due to the high frequency of carriers)\n- Do not cross two carriers: 25% risk of lethal affected homozygotes\n- A carrier may be crossed with a clear animal; offspring intended for breeding must be tested\n- Progressively replace carriers with clear offspring without narrowing the gene pool\n- Warn breeders of breeds derived from the Standard poodle of the risk of carrying the allele

Differential diagnosis with other neonatal encephalopathies (neonatal hypoglycaemia, sepsis, toxoplasmosis, other storage diseases) and with idiopathic cerebellar hypoplasia. MRI shows a reduced brain, ventriculomegaly, white matter abnormalities and abnormal cerebellar morphology; neuropathology describes cerebellar dysplasia with dysplastic foci of mixed granular and Purkinje cells, and neuronal migration abnormalities in the subventricular zone. There is no effective treatment.

1. Chen X et al. (2008) A neonatal encephalopathy with seizures in Standard Poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics 9:41-49. PMID: 18074159