What is Neonatal Encephalopathy in dogs?

Neonatal Encephalopathy (also known as Neonatal Encephalopathy With Seizures (NEWS)) is an autosomal recessive neurological disease that makes its effects felt in the first few days of life and is fatal to affected puppies by 7 weeks of age. This terrible disease affects the development of the puppy’s brain and nervous system with most puppies succumbing from its effects within days of being born.
 

Genetics of Neonatal Encephalopathy in dogs

Neonatal Encephalopathy is an autosomal recessive disease, meaning that the affected puppies must inherit one mutated copy of the ATF2 gene responsible from each carrier parent (one from carrier mum and one from carrier dad). If either of the parents bred together to produce puppies are clear of Neonatal Encephalopathy, then none of the offspring will be affected by the disease. If both of the parents are carriers of the mutated genes, about one quarter of the puppies will be affected by Neonatal Encephalopathy. The ATF2 gene encodes Activating Transcription Factor (ATF) number 2. This compound is part of the cell response to a number of stimuli and the mutation prevents this process from happening to the extent required by the body and especially by the central nervous system. The mutation responsible was discovered at the University of Missouri by a research team led by Drs Dennis O’Brien and Gary Johnson.

Severity of Neonatal Encephalopathy in dogs

This disease is of the highest severity as it has a 100% fatality rate in affected dogs with no recorded puppies surviving past 7 weeks of age.

What are the symptoms of Neonatal Encephalopathy in dogs?

The symptoms of Neonatal Encephalopathy present very early in the life of affected puppies and usually begin in the first days of life. Affected puppies are much smaller than their littermates and have the overall appearance of weak puppies failing to thrive. The affected puppies surviving past their first week will develop ataxia, tremors over the whole body that progress very quickly into clonic-tonic seizures. They are weak and have trouble walking around and are noticeably mentally challenged when compared to other pups in the litter. When autopsies have been performed on affected puppies, some brain structure differences have been observed. Often but not always, the cerebellum (responsible for coordination) and the cerebrum (thought to produce seizures when damaged or malformed) have a reduced size or even changed in terms of the organisation of parts within these structures.

Diagnosis of Neonatal Encephalopathy in puppies

Diagnosis of Neonatal Encephalopathy was often a matter of eliminating all of the other potential causes of the symptoms. This was an almost exhausting list from low blood sugar, shunts, metabolic conditions and even injury. The availabilily of DNA Disease Screening using the work of Drs Johnson and O’Brien means that a definitive diagnosis can be made quickly. This DNA Disease Screening also allows breeders to identify carriers and clear dogs to reduce the possibility of breeding affected puppies.

Treatment of Neonatal Encephalopathy in dogs

Unfortuantely there are no real treatments for dogs affected by Neonatal Encephalopathy and intensive nursing care has so far only been helpful to extend the life of affected dogs by a few weeks. Most breeders who breed a puppy with Neonatal Encephalopathy will ultimately euthanize the puppy to avoid any unnecessary suffering. This heartbreaking decision is not made lightly but all affected dogs do not live past a couple of months. DNA testing offers the ability to screen dogs before breeding to avoid this situation.

References

Chen Xuhua; Johnson Gary S; Schnabel Robert D; Taylor Jeremy F; Johnson Gayle C; Parker Heidi G; Patterson Edward E; Katz Martin L; Awano Tomoyuki; Khan Shahwanaz; O’Brien Dennis P (2008).   A neonatal encephalopathy with seizures in standard poodle dogs with a missense mutation in the canine ortholog of ATF2. Neurogenetics 9(1):41-9
Alderliesten T et al (2012) Antemortem cranial MRI compared with postmortem histopathologic examination of the brain in term infants with neonatal encephalopathy following perinatal asphyxia.Arch Dis Child Fetal Neonatal Ed
Mortality and Causes of Death, Collaborators (17 December 2014). “Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.”. Lancet.
Neonatal Encephalopathy. https://www.adhb.govt.nz/