The condition known as Benign Juvenile Epilepsy/Juvenile Epilepsy (BJE/JE) was first researched and identified as a probable inherited condition by the pioneer breeders in the UK. Puppies were observed with seizures and ataxia usually between 5 and 13 weeks of age. The condition was described initially by the LRCGB as Cerebellar Anomaly.
In June 2008 the LRCGB initiated a Club scheme to eventually eradicate the mutant gene. First clinical investigations were carried out in the late 1990s at Stone Lion clinic, London. As a result of the efforts by the LRCGB to publicise the existence of this hitherto unreported condition, investigations were subsequently performed in several countries, notably Finland, and a DNA-based test for carriage of the condition (renamed Juvenile Epilepsy) has been available since May 2008.
The development of the test made it appear that the epilepsy may (at least in some cases) be distinct from another inherited neurological problem affecting Lagotto of similar age but with slightly different clinical signs. In these cases, weakness, tremors, and an inability to control limbs are prominent features. These neurological deficits are sometimes more severe and accompanied by foreshortened muzzles. However, it should be noted that the parents of the UK-bred puppies showing these more severe signs were the result of two clinically normal dogs (as pups and adults) being mated, both of which subsequently tested affected (homozygote) for the Juvenile Epilepsy mutation. Both syndromes are accompanied by changes in a part of the brain known as the cerebellum. This second disease is still known as Cerebellar Anomaly, Cerebellar Ataxia or Cerebellar Abiotrophy.
Inherited Benign Juvenile Epilepsy resembles idiopathic childhood epilepsies with benign outcomes in humans. Clinical and diagnostic evaluations of affected dogs including electromyography, electroencephalography and other testing indicated that seizures in puppies begin at 5 to 9 weeks of age and usually resolve by 8 to 13 weeks. There are some adult-onset cases in the breed too. Dogs with the most severe seizures also have other neurological signs such as generalized ataxia and hypermetria. Routine laboratory screenings of blood, urine, and cerebrospinal fluid did not reveal abnormalities. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging (MRI) remain normal in analysed dogs. However, most affected puppies and adult cases revealed epileptiform activity in the electroencephalogram (EEG). Histopathologic examination showed cerebellar lesions in two studied Lagotto. Pedigree analysis suggests an autosomal recessive mode of inheritance.
The study of the genetics of Juvenile Epilepsy in Lagotto led to the causative gene being identified. If a dog carries one copy of the mutations it can transfer the gene defect to approximately 50% of its offspring. If the dog has two copies of the mutation it transfers the defect to all of its offspring. It is recommended that dogs that are homozygous (i.e. carry two copies of the defective gene) for the Lagotto epilepsy mutation are withdrawn from breeding programmes. Normal and carrier dogs can be used but carrier dogs may only be mated to normal dogs, either tested or hereditary clear. Although the situation of a dog having “Hereditary Clear” status (i.e. neither of its parents carry the defective gene so he cannot carry it) exists, from January 2022 the Kennel Club will limit this status to two generations, testing individuals will then have to be undertaken.
The diagram at the end of the section on Lysosomal Storage Disease (LSD) shows how carrier and non-carrier genes are passed to offspring, in our case, puppies. It is important to remember, however, that despite the implied average inheritance, each puppy will be the product of its own individual roll of the genetic dice and therefore the percentage values are not absolute.
If you wish to have your dog tested for BJE/JE, please contact the Chair of the Club’s Health Sub-Committee.