Epilepsy gene discovered - Munich, 21.02.2017 Ludwig-Maximilian-Universität München

Seizures are relatively common in dogs. Now animal neurologists have been able to clearly define a genetic trigger for a specific form of epilepsy in Ridgebacks.

Rhodesian Ridgebacks were originally bred to hunt lions. That sounds extremely robust. However, these large, powerful dogs are not immune to serious illnesses: up to two percent of Ridgebacks suffer from a certain form of epilepsy. It begins in adolescent dogs with frequent, initially inexplicable muscle twitches. Around a third of the affected animals then also develop severe grand mal seizures as the disease progresses. The scientists were able to show that the dogs suffer from generalized myoclonic epilepsy using a new type of video EEG that was specially modified for use in dogs. This method enables the simultaneous recording of brain signals and the activity of the dogs.

An international team of scientists has now found a genetic cause for this particular disorder - a defect in a gene that apparently plays an important role in the modulation of the neurotransmitter acetylcholine. A whole series of epilepsy genes are already known in dogs that intervene in a presumably multifactorial process. However, the genetic defect that has now been discovered is inherited in an autosomal recessive manner: if two dogs that carry the defective gene are crossed with each other, part of the litter will definitely be affected by the disease. The team led by Professor Andrea Fischer, neurologist at the LMU Small Animal Clinic, and Professor Hannes Lohi, molecular geneticist at the University of Helsinki, Finland, together with Professor Fiona James from the University of Guelph, Canada, human physicians and animal neurologists, have now reported their findings in the renowned scientific journal PNAS.

Epilepsy is the most common chronic neurological disease in dogs - with a high genetic contribution to its development due to advanced breeding. Many dog breeds can be traced back to a small number of "founder" individuals and form their own population with a very homogeneous phenotype and very limited genetic diversity. This means that once introduced, genetic defects persist for a long time. Scientists have even developed a genetic test for the form of epilepsy now described in Ridgebacks. The disease can be avoided if Rhodesian Ridgebacks are genetically tested before breeding. As long as only one parent carries the gene, epilepsy will not occur. Only when both male and female dogs are carriers of the gene the puppies will develop epilepsy. According to Fischer, genetic testing and video EEG also help to identify and treat Rhodesian Ridgebacks suffering from epilepsy as early as possible.

In the present case, the scientists also hope to gain insights for human medicine from further investigations: the gene in which the defect can occur in dogs has a counterpart in the human genome. According to Lohi and Fischer, this could therefore be a candidate for an epilepsy gene in humans. This is because the symptoms of the epilepsy variant described can also be compared with juvenile myoclonic epilepsy (JME), one of the most common forms in humans, the scientists write: the convulsions in both forms are bilateral, rhythmic and sometimes asymmetrical and affect the upper limbs and trunk. The patterns in the EEG are similar. And both forms are associated with a strong sensitivity to light, as examinations of affected Rhodesian Ridgebacks by neuropaediatricians at the Vogtareuth Epilepsy Center have shown. In addition, they show a strong dependence on the sleep-wake rhythm. Further studies could not only help to elucidate the pathophysiology of myoclonic epilepsies, which is still poorly understood, but could also possibly reveal approaches for new therapies. 

PNAS 2017