OMIA:001596-9615 : Epilepsy, benign familial juvenile in Canis lupus familiaris (dog)

Categories: Behaviour / neurological phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608301 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant with incomplete penetrance

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Benign familial juvenile epilepsy; remitting focal epilepsy; benign juvenile epilepsy syndrome; juvenile epilepsy

Species-specific symbol: BFJE

Inheritance: Seppälä et al. (2011): "BFJE is transmitted in imperfect Mendelian fashion. In the vast majority of cases, 93%, homozygous mutation is required for the disease to manifest. In a minority, 7%, heterozygosity suffices. Conversely, 1.8% of dogs may be resistant to seizing despite homozygous mutation. Finally, we found no dog with homozygous wt genotype at Lgi2 c.1552 that has BFJE."

Mapping: By conducting a GWAS on 11 discordant sib-pairs (7 full-sibs and 4 half-sibs) of the Lagotto romagnolo breed, each genotyped with the Affymetrix's Canine SNP Array version 1 (yielding 17,273 informative SNPs for analysis), Seppälä et al. (2011) mapped this disorder to a region on chromosome CFA3. Subsequent homozygosity mapping narrowed the region to 1.7Mb between 87.3 and 89.0Mb, which contains 9 genes.

Molecular basis: By sequencing the most likely of 9 positional candidate genes (see Mapping section), Seppälä et al. (2011), part of the LUPA consortium, discovered that this type of epilepsy in the Lagotto romagnolo breed is due to a nonsense mutation (c.1552A>T (p.K518X)) in the gene for LGI2. Noting that mutations in this gene have not yet been reported to be causative of epilepsy in humans, but that mutations in a "sister" gene, LGI1, result in lateral temporal lobe epilepsy in humans, the authors go to considerable lengths to describe how this discovery in dogs may well inform future studies of the genetic basis of epilepsy in humans.

Clinical features: BFJE is characterised by juvenile-onset seizures beginning at five to nine weeks of age and typically spontaneously remit by thirteen weeks of age (Jokinen et al., 2007). Affected puppies exhibit generalised tremor, ataxia and stiffness during seizures and severe cases show neurological signs such as ataxia and hypermetria between epileptic episodes (Jokinen et al., 2007). Seizures can occur at any time of the day and the puppy may or may not be conscious during the episode (Jokinen et al., 2007). Following remission, BFJE-affected puppies often show behavioural abnormalities in adulthood, including increased inattention and excitability (Jokinen et al., 2015). On rare occasions, the patient may experience seizures years after remission, or develop progressive neurological disorders that eventually require euthanasia (Jokinen et al., 2015). BFJE puppies show epileptiform activity on electroencephalogram, both during and in between epileptic episodes. IT thanks DVM student Tina Gong, who provided the basis of this contribution in May 2023.

Pathology: Affected dogs have a relatively small cerebellum and intracytoplasmic inclusion bodies in cerebellar Purkinje cells (Jokinen et al., 2007). IT thanks DVM student Tina Gong, who provided the basis of this contribution in May 2023.

Breed: Lagotto Romagnolo (Dog) (VBO_0200804).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LGI2 leucine-rich repeat LGI family, member 2 Canis lupus familiaris 3 NC_051807.1 (86155381..86187875) LGI2 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
269 Lagotto Romagnolo (Dog) Epilepsy, benign familial juvenile LGI2 nonsense (stop-gain) Naturally occurring variant CanFam3.1 3 g.85210442A>T c.1558A>T p.(K520*) XM_022416405.1; XP_022272113.1; published as c.1552A>T & p.(K518*); coordinates in the table have been updated to a recent reference genome and / or transcript 2011 21829378

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001596-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :
Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787. DOI: 10.1186/s13059-023-03023-7.
2016 Uriarte, A., Maestro Saiz, I. :
Canine versus human epilepsy: are we up to date? J Small Anim Pract 57:115-21, 2016. Pubmed reference: 26931499. DOI: 10.1111/jsap.12437.
2015 Jokinen, T.S., Tiira, K., Metsähonkala, L., Seppälä, E.H., Hielm-Björkman, A., Lohi, H., Laitinen-Vapaavuori, O. :
Behavioral abnormalities in Lagotto Romagnolo dogs with a history of benign familial juvenile epilepsy: A long-term follow-up study. J Vet Intern Med 29:1081-7, 2015. Pubmed reference: 25945683. DOI: 10.1111/jvim.12611.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
Ekenstedt, K.J., Oberbauer, A.M. :
Inherited epilepsy in dogs. Top Companion Anim Med 28:51-8, 2013. Pubmed reference: 24070682. DOI: 10.1053/j.tcam.2013.07.001.
2011 Seppälä, E.H., Jokinen, T.S., Fukata, M., Fukata, Y., Webster, M.T., Karlsson, E.K., Kilpinen, S.K., Steffen, F., Dietschi, E., Leeb, T., Eklund, R., Zhao, X., Rilstone, J.J., Lindblad-Toh, K., Minassian, B.A., Lohi, H. :
LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet 7:e1002194, 2011. Pubmed reference: 21829378. DOI: 10.1371/journal.pgen.1002194.
2007 Jokinen, T.S., Metsähonkala, L., Bergamasco, L., Viitmaa, R., Syrjä, P., Lohi, H., Snellman, M., Jeserevics, J., Cizinauskas, S. :
Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Intern Med 21:464-71, 2007. Pubmed reference: 17552452.

Edit History

  • Created by Frank Nicholas on 12 Aug 2011
  • Changed by Frank Nicholas on 12 Aug 2011
  • Changed by Frank Nicholas on 29 Aug 2011
  • Changed by Frank Nicholas on 07 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 May 2013
  • Changed by Imke Tammen2 on 03 Feb 2023
  • Changed by Imke Tammen2 on 03 May 2023