Pug Dog Encephalitis (PDE)
Acronym: | PDE, NME |
Gene: | DQB1 |
Mutation: | PDE/NME associated |
Inheritance: | Autosomal Recessive |
Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Pug Dog Encephalitis (PDE), also known as necrotizing meningoencephalitis (NME), is an inherited brain disease affecting pug dogs. It is described as an aggressive and fatal inflammatory disease of the central nervous system. The first diagnosis of necrotizing meningoencephalitis (NME) in a dog was reported in 1960-ih, but the disorder was not understood until many years later. Due to sharing many similarities with meningitis in humans, a viral cause was suspected. However, thorough molecular examinations have ruled out infectious causes and it is established that pug dog encephalitis is an immune-mediated disease, which occurs as a result of genetic susceptibility. Until today, necrotizing meningoencephalitis has been described in several toy breed dogs, such as the Brussels Griffon, Chihuahua, Coton de Tulear, Maltese, Papillon, Pekingese, and Shih Tzu.
Pug dog encephalitis, unlike other forms of encephalitis, is hereditary and immune-mediated. Immune-mediated diseases are characterized by the abnormal immune response, in which the body’s immune system recognizes healthy body tissues as dangerous and attacks them. In a PDE case, the immune system is attacking the brain, causing its painful inflammation. The first symptoms usually occur between 2 and 3 years of age. Although symptoms most commonly appear around that age, there were reported cases of dogs affected already at 6 months of age but also 7 years of age. Symptoms include seizures, loss of muscle coordination, walking in circles, head tilt, and pressing the head against walls or objects. Behavioral changes can be observed as well, such as lethargy, confusion, depression, or aggression. Usually, after the development of the first symptoms, the disorder progresses rapidly, and affected dogs die within months after the onset of symptoms. Although the disorder is deadly, there are some medications that can ease the symptoms. Seizures can be controlled with anti-convulsants, while painful brain inflammation can be reduced thanks to anti-inflammatory drugs, such as corticosteroids. After the development of symptoms, the disease can be diagnosed by a veterinarian through tests such as CAT scans and MRIs. Unfortunately, the disorder progresses so fast that sudden death onsets or euthanasia is required, which leaves little time for diagnostic tests.
Pug Dog Encephalitis (PDE) is associated with 3 specific dog leukocyte antigen (DLA) class II genes: DRB1, DQA1, and DQB1. The Mode of PDE inheritance seems to be complex, however, it has been observed that only dogs with two copies of the PDE susceptibility-associated markers have a high risk of developing the symptoms in their lifetime. Research has established that approximately 1.2% of Pug dogs die of encephalitis, whereas susceptibility markers in the homozygous or heterozygous state are present in approximately 50% of the Pug population. Due to this high percentage, it is not advised to completely remove carriers from the breeding program, since it would lead to a significant loss of genetic diversity. Considering homozygosity for a specific allele greatly increases the risk of developing symptoms, selective mating against homozygosity is preferred. PDE genetic testing allows the identification of two heterozygous dogs, which can prevent their breeding and obtain of homozygous puppies.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Barber RM et al. (2011): Identification of risk loci for necrotizing meningoencephalitis in Pug dogs. J Hered.
Pederson, N. (2011): Dog leukocyte antigen class II-associated genetic risk testing for immune disorders of dogs: simplifies approaches using Pug dog necrotizing meningoencephalitis as a mode. J Vet DIagn Invest 23:68-76.
Schrauwen I, Barber RM, Schatzberg SJ, Siniard AL, Corneveaux JJ, Porter BF, et al. (2014) Identification of Novel Genetic Risk Loci in Maltese Dogs with Necrotizing Meningoencephalitis and Evidence of a Shared Genetic Risk across Toy Dog Breeds. PLoS ONE 9(11): e112755. doi:10.1371/journal.pone.0112755