Juvenile epilepsy test for Lagotto Romagnolos

Jokinen et al. (2007) described recently a new epileptic syndrome in the Lagotto breed of dogs. Clinical studies indicated that these dogs suffer from inherited benign juvenile epilepsy, which resembles idiopathic childhood epilepsies with benign outcomes in human. Clinical and diagnostic evaluations of affected dogs including electromyography, electroencephalography, and other testing indicated that seizures of 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 neurologic 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 analyzed dogs. However, most affected puppies and adult cases revealed epileptiform activity in the electroencephalogram (EEG). Histopathologic examination shows cerebellar lesions in two studied lagottos. Pedigree analysis suggests an autosomal recessive mode of inheritance.

We have studied the genetics of the juvenile epilepsy in Lagottos and have recently identified the causative gene (not published yet). If a dog carries one copy of the mutation 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 It is recommended that dogs that are homozygous for the lagotto epilepsy mutation are withdrawn from breeding programs. Normal and carrier dogs can be used in breeding but it is advised to choose mutation-free partners for carriers.

Dogs that are homozygous for the mutation become affected. However, there has been few individual cases reported where carriers showed BFJE like symptoms. There could be several reasons for this including the following: The affected carrier dog has a second mutation in the same gene (all coding regions have been excluded though), the carrier dog has a mutation in another gene, or heterozygosity for the mutation lowers the seizure threshold in some individuals in certain conditions. There is a research project going on to identify the reason for seizures in carrier dogs. If your dog is tested carrier but it shows epileptic symptoms, please contact our customer service or the research group for further investigation. We are looking for more ataxia and adult-onset epilepsy cases from the breed to study the genetics of these disorders.

Besides the benign juvenile epilepsy the breed suffers also from two other similar conditions; juvenile progressive ataxia (cortical abiotrophy) and another form of epilepsy. These two condition are not related to the identified mutation. The research on these phenotypes continues in the University of Helsinki.

The results are reported as follows:

NORMAL: The dog carries two copies of the normal gene and therefore has no predisposition for juvenile epilepsy.

CARRIER: The dog carries one mutant and one normal copy of the juvenile epilepsy gene. The dog will not develop the disease but can pass over the defect to approximately 50% of its offspring.

AFFECTED: The dog carries two mutant copies of the epilepsy gene and will most likely develop the disease in early puppyhood.

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Reference:

Jokinen T, Metsahonkala L, Bergamasco L-A, Viitmaa R, Syrja P, Lohi H, Snellman M, Jeserevics J, and Cizinauskas S. Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs, J Vet Int Med, 21(3):464-71,2007.

Jokinen TS, Rusbridge C, Steffen F, Viitmaa R, Syrjä P, De Lahunta A, Snellman M, Cizinauskas S. Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs. J Small Anim Pract. 2007 Aug;48(8):470-3.

Seppälä EH, Jokinen TS, Fukata M, Fukata Y, Webster MT, Karlsson EK, Kilpinen S,Steffen F, Dietschi E, Leeb T, Eklund R, Xiaochu Z, Rilstone J, Lindblad-Toh K, Minassian BA and Lohi H. LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet. 2011 Jul;7(7):e1002194. Epub 2011 Jul 28.