Neonatal Encephalopathy with Seizures

Neonatal encephalopathy with seizures is a pathology that affects the cerebellum, making it smaller than usual and presenting unusual clusters of Purkinje neurons and other cerebellar cells.

Symptoms

This is a severe disorder in which puppies are often small at birth, have difficulty feeding and fail to thrive. In addition, they develop neurological symptoms such as ataxia, muscle weakness, seizures and tremors. The puppies do not respond adequately to external stimuli and do not interact with the rest of the puppies in the litter or with their mother. Their life expectancy usually does not exceed 7 weeks of age.

Disease Management

Unfortunately, there is no treatment for this disease. Due to the severity of the symptoms, affected puppies are usually euthanized.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Activating transcription factor 2 (ATF2) is a factor that regulates the expression of many genes and has been associated with multiple pathologies affecting various organs and tissues, including liver, kidney, pancreatic and neurodegenerative diseases, among others. It is suggested that the ATF2 gene may be involved in the neuronal migration that takes place during canine brain development. The genetic variant causing this encephalopathy was identified by Chen et al. in 2008 in poodle dogs. It is a nonsense variant c.152T>G (p.Met51Arg) in exon 3 of the ATF2 gene that in homozygosis alters the function of the ATF2 transcription factor causing the disease.

Most affected breeds

Standard Poodle

Bibliography

Chen X, Johnson GS, Schnabel RD,et al. A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics. 2008 Feb;9(1):41-9.

Yu Y, Hasegawa D, Chambers JK,et al. Magnetic Resonance Imaging and Histopathologic Findings From a Standard Poodle With Neonatal Encephalopathy With Seizures. Front Vet Sci. 2020 Nov 10;7:578936.