A DNA Test for Neonatal Encephalopathy

Dennis O’Brien, DVM, PhD, Gary Johnson, DVM, PhD, and Liz Hansen, BS

University of Missouri College of Veterinary Medicine


Mission Accomplished! With support from the AKC/Canine Health Foundation, the Poodle Club of America, the St Joseph Missouri Kennel Club, and individual Standard Poodle owners, researchers at the University of Missouri-Columbia have been investigating a previously undescribed fatal developmental brain disease in an extensive family of Standard Poodles. The disease is inherited as an autosomal recessive trait, and most affected puppies die shortly after birth. With intensive nursing care, affected pups can be kept alive for a few weeks; however, none have survived past their fifth week. We are pleased to announce that we have mapped the disease locus, identified the mutant gene and the mutation causing the disease, and devised a DNA test which distinguishes normal, carrier, and affected Poodles. A manuscript detailing these findings is being prepared for publication in the scientific literature.

Effective immediately, we are making the DNA test available to Standard Poodle owners. We validated the DNA test by analyzing all 91 of the Standard Poodle samples already in our collection. Owners who have already sent us a blood sample from their Standard Poodle and would like to know the test result may contact us by email (HansenL@Missouri.edu) and will be provided the result without charge. The testing fee for new samples is $40 per dog. Instructions and a form to send with the sample to be tested are in the “sample submission” section of the project website, www.CanineGeneticDiseases.net/ataxia. Funds generated from this testing will be applied to the development of DNA tests for other heritable canine diseases. To avoid producing affected puppies, we encourage all breeders to test their Standard Poodles before they are bred, and to refrain from breeding two carriers to each other. Breeders who follow this advice will not produce affected puppies in their litters. Now that we better understand of the cause of this disease, we would like to examine a few more newborn affected puppies. Therefore, we will test all pregnant Standard Poodles at no charge until the end of May, 2006.


How Our Research Began

In 1997, we examined two five-week-old Standard Poodle pups suffering from difficulty walking and seizures. Their littermates were developing normally.Treatment of the seizures was unsuccessful, and the affected pups were euthanized. Subsequently, more than 14 litters with pups showing identical clinical signs have been identified by veterinary neurologists in various areas of the country.



Pup with neonatal encephalopathy. The affected pup in the background is clearly smaller than her normal littermate in front. She is unable to stand and her movements are uncoordinated.

Click picture for video clip.

What is Neonatal Encephalopathy?

“Neonatal” refers to the time immediately after birth. “Encephalopathy” refers to a disease affecting the brain. Thus Neonatal Encephalopathy means a disease of the brain that becomes apparent soon after pups are born. Affected pups have been weak, uncoordinated, and mentally dull from birth. If they survive the first few days, they nurse adequately. They may not, however, be able to compete with stronger pups in the litter and their growth may be stunted. Some cannot stand at all. Others manage to struggle to their feet and walk with jerky movements, falling frequently. Seizures develop in most affected pups at 4-5 weeks of age. Attempts to control these seizures with medication have proven futile, and the pups die or are euthanized before they reach weaning age.

Post-mortem examinations have been performed on some affected puppies. While no changes were found in the first brains examined, more recent examinations have found changes in organization of the portion of the brain responsible for coordination (the cerebellum) and possibly in the area of the brain that would produce seizures (the cerebrum).

What other diseases might look similar?

A number of brain diseases of young dogs could produce similar signs, so it is important to avoid confusing every “funky puppy” with this specific disease. Low blood sugar can produce dullness and seizures in pups who aren’t nursing well or who have congenital problems regulating their blood sugar. The low sugar levels would be apparent on routine blood tests taken when the pup is showing clinical signs. Liver shunts can cause altered behavior, coordination difficulties, and sometimes seizures. Abnormal liver function would also be apparent on appropriate blood tests, and the shunt would be found at post-mortem examination. Hydrocephalus (water on the brain) or other congenital malformations of the brain could produce similar signs, but such problems would be readily apparent at post-mortem examination. Infections either while in the uterus or immediately after birth can cause brain damage, but would typically affect the entire litter. Inflammation would be apparent in the brain at post-mortem. Certain infections of the dam (involving toxin-producing bacteria, for example) also would be expected to affect a large percentage of the litter.

What remains to be done?

Our primary goal was to create a DNA test that identifies Standard Poodle carriers of the mutation so that Standard Poodle breeders can avoid producing affected puppies by never breeding two carriers together. As mentioned above, our primary goal has been accomplished. Nonetheless, some interesting and important scientific questions with implications for both human and canine health still remain to be answered. Thus, any breeder who has recently bred their female Standard Poodle may have her tested at no charge (offer good through the end of May, 2006). If she is a carrier, we will also offer a free test to the mate to determine if he is also a carrier and the puppies are at risk of having the encephalopathy. If, in fact, some affected pups are expected, we would like an opportunity to examine them.

Standard Poodle breeders now have a tool that will allow them to avoid producing affected puppies in future litters. We encourage owners to test all dogs that are being considered for breeding. We would like to thank the AKC/Canine Health Foundation, the Poodle Club of America, the St Joseph Missouri Kennel Club, and individual Standard Poodle owners who provided DNA samples and in some cases financial support for the project. Much of the laboratory work was done by Ms Xuhua Chen and will appear in her Masters thesis.

posted 03-27-06