Benign Familial Juvenile Epilepsy

Benign familial juvenile epilepsy is a neurological disorder in which dogs are predisposed to seizures from a few weeks of life and whose symptoms are highly variable.

Symptoms

The first symptoms usually appear between 5 and 9 weeks of age and include tremor, ataxia (involuntary movements affecting gait and balance) and stiffness. Seizures can occur at any time of the day, even during sleep, and their frequency and intensity is highly variable from puppy to puppy. Some dogs may remain conscious during seizures while others may become unconscious.

Disease Management

Antiepileptic drugs can be used to prevent seizures or at least to try to reduce their severity and frequency. Phenobarbital, imepitoin and potassium bromide are three drugs that have been approved for the treatment of epilepsy in dogs in Europe, and primidone in the U.S. Affected dogs are usually treated for life and require routine follow-ups.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

In recent years it has been observed that canine idiopathic epilepsy may have a proven or suspected genetic background in several purebred dogs. The prevalence of epilepsy in the general canine population is estimated to be 0.6% to 0.75%. The LGI2 gene produces a protein that is expressed in neurons and is highly conserved in mammals and has been shown to start to be produced especially during postnatal brain development, reaching constant values in the adult brain. Seppälä et al. observed that alterations in the LGI2 gene can lead to a lack of LGI2 secretion and since LGI2 may be involved in brain protection against seizures during neurodevelopment. The g.85210442A>T, c.1558A>T or p.(K520*) mutation (initially described as c.1552A>T) by Seppälä et al. was observed in homozygosity in Lagotto Romagnolo dogs with the disease, indicating that it was a possible causative variant of the pathology and that its mode of inheritance is autosomal recessive.

Most affected breeds

Lagotto Romagnolo

Bibliography

Jokinen TS, Metsähonkala L, Bergamasco L,et al. Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Intern Med. 2007 May-Jun;21(3):464-71.

Löscher W. Dogs as a Natural Animal Model of Epilepsy. Front Vet Sci. 2022 Jun 22;9:928009.

Seppälä EH, Jokinen TS, Fukata M et al. LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet. 2011 Jul;7(7):e1002194.

Uriarte A, Maestro Saiz I. Canine versus human epilepsy: are we up to date? J Small Anim Pract. 2016 Mar;57(3):115-21.