Do Mild, Infrequent Seizures Constitute Inherited Idiopathic Epilepsy in Dogs?
Tufts' Canine and Feline Breeding and Genetics Conference, 2005
Barbara Licht, PhD1, Linda Hyson, BA1, Shili Lin, PhD2, Kathleen Harper, DVM, PhD3, Mark Licht, PhD1, Yuqun Luo, PhD4, Soledad Fernandez, PhD5
1Dept. of Psychology, Florida State Univ. (FSU), Tallahassee, FL; 2Dept. of Statistics, Ohio State Univ. (OSU), Columbus, OH; 3Laboratory Animal Resources, FSU, Tallahassee; 4Dept. of Epidemiology & Biostatistics, Case Western Reserve Univ., Cleveland, OH; 5Center for Biostatistics, OSU, Columbus, OH

Findings by our group suggest that when examining the mode of inheritance for "idiopathic" epilepsy, dogs with very infrequent and/or mild seizures should be included along with the more severe cases. Because mild, infrequent seizures rarely warrant treatment, the importance of these cases often is discounted. However, we have found that even very mild cases may provide crucial information on the inheritance of idiopathic epilepsy. (Note that if seizures of any severity are known to be due to another disease/disorder, such as liver disease, head trauma, an infectious disease such as distemper, etc., then the seizures would not be considered "idiopathic" epilepsy.)

Let us consider a case of an otherwise healthy dog that had two mild seizures several months apart. The owner reported that the dog staggered around as if drunk (but did not fall), drooled, and acted disoriented for 2-3 minutes. Understandably, many veterinarians would not diagnose this as epilepsy because it would not require treatment and because it is not possible to know with 100% certainty if these mild episodes are seizures. Further, many experienced dog owners and breeders may not even realize that these episodes are most probably seizures. In fact, these mild episodes often are never reported to the breeder, even when the owner has frequent contact with the breeder. Breeders find out about such episodes only when they (or a researcher) directly ask the owner if their dog ever had seizures or episodes of unusual behavior. Thus, when breeders try to evaluate if their bloodlines show any evidence of inherited epilepsy, they often do not even know about these mild cases. Importantly, as illustrated by the information presented below, mild cases often occur in the same families as the more severe, clear-cut cases of epilepsy; and if only the more severe cases are considered, breeders and researchers are likely to miss seeing a clear inheritance pattern. Thus, what may, in fact, be a simple recessive disorder may appear to be due to a more complex mode of inheritance, or worse, no inheritance at all.

In a large pedigree of Standard Poodles that we analyzed, we considered any Poodle to be "affected with idiopathic epilepsy" if all of the following three conditions held:

1.  The Poodle had one or more episodes for which the owner's description was judged by our research staff to be a seizure. We included very clear seizures that would be considered "grand mal" (technically called "generalized tonic-clonic" seizures), as well as much milder episodes that we judged to be "focal" or "partial" seizures. (These are called "focal" or "partial" seizures because the seizure involves only a limited area of the brain.) These milder episodes included the example given above as well as other episodes, such as trembling and hiding (for no reason), uncontrolled repetitive lifting of leg(s) in a manner similar to a marionette, etc. In most of these episodes, the dog's consciousness was impaired, but it was never completely lost (as assessed by asking owners to rate dog's responsiveness to them during the worst part of the episode). We judged these milder episodes to be seizures because they strongly resemble episodes seen in humans that have been verified with electroencephalograms (EEGs) to be "focal" seizures.

2.  The Poodle's first observed seizure occurred younger than 8 years of age. In this family, the average (mean) age when seizures began was 3.7 years, with the youngest being 6 months and the oldest being 7 years.

3.  There was no evidence of any illness or injury that was likely to have caused the seizures.

Based on these criteria, there were 27 Poodles that were considered to be affected with idiopathic epilepsy. There were 57 that were not affected; that is, the owner was certain that they never observed any potential seizure activity. There were 38 Poodles for whom we either had no information (couldn't contact owner) or, in a few cases, the information was too unclear to classify the dog as affected or unaffected. What was compelling about this family is that the data are consistent with a simple recessive mode of inheritance. Statistical tests using formal segregation analysis showed that the best model was simple recessive (with complete or almost complete penetrance and a gene frequency of 0.39). A visual inspection of the pedigree (included in poster) also revealed a simple recessive mode of inheritance. For example, when an unaffected sire that was suspected of being a "carrier" was bred to an affected bitch, an average of 45% of their offspring were affected. (The expected frequency based on simple recessive inheritance would be 50%.) Similarly, when two probable "carriers" were bred together, 33% of their offspring were affected. (Expected frequency for offspring of two carriers is 25%.)

In contrast, many fewer dogs were classified as being affected with idiopathic epilepsy when we considered only "grand mal" seizures, which involved uncontrolled shaking and/or rigidity of the entire body and complete loss of consciousness. Specifically, if we only consider as affected dogs with two or more grand mal seizures, 10 Poodles would be classified as affected. This constitutes only 37% (10/27) of the number we considered to be affected when we also included the milder cases. Thus, if we only considered Poodles with grand mal seizures to be affected, we would not have found as clear a pattern of inheritance. In fact, one argument that some breeders and owners have presented to us for why they believe that idiopathic epilepsy is not inherited in a clear fashion, or not inherited at all, is that there are too few cases in some supposedly affected bloodlines for it to be inherited as a simple recessive trait. Based on our data, we offer another potential explanation for why epilepsy often does not appear to be inherited with a clear mode of inheritance. We suggest that it is because many cases are either not brought to the attention of the breeder (or researcher) and/or their seizures are dismissed as too mild or infrequent to be indicative of idiopathic epilepsy. Of course, until we or other researchers discover the gene (or genes) for epilepsy in Poodles and other breeds, it will not be possible to know the mode of inheritance with certainty. However, we argue that the kind of mild cases described here should be considered "affected" not only because they strongly resemble focal seizures seen in humans, but because it was only when these mild cases were analyzed along with the more severe cases that a clear mode of inheritance emerged. Perhaps, both severe and mild cases are found in the same families because in addition to the gene responsible for whether the dog has epilepsy, there may also be a "modifier" gene that affects the severity of seizures. Last, but importantly, we wish to thank the breeder who provided us with complete litter records. Without complete litter records, we would not have been able to collect enough data on this bloodline to determine a clear mode of inheritance.

Speaker Information
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Barbara Licht, PhD
Dept. of Psychology, Florida State Univ. (FSU)
Tallahassee, FL

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