Benign juvenile epilepsy of the Lagotto romagnolo, with imperfect Mendelian inheritance (autosomal dominant with incomplete penetrance) and caused by a loss-of-function mutation in LGI2. It presents with focal seizures of very early onset (5-9 weeks) and resolves spontaneously by around 4 months in most puppies. It is considered a natural model of human infantile remitting epilepsies linked to the LGI1/LGI2 pathway.

Affected breed: Lagotto romagnolo. Limited data on the exact frequency of carriers and cases.

- Focal seizures with head/facial movements and tremor
- Brief episodes with preserved or mildly altered consciousness
- Interictal ataxia in some puppies
- Onset around 5-9 weeks of life
- Spontaneous remission by around 4 months in many cases
- Some animals have persistent seizures

Clinically described by Jokinen et al. (2007) in the Lagotto romagnolo as benign familial juvenile epilepsy. In 2011, Seppälä et al. identified, by GWAS and homozygosity mapping on canine chromosome 3, a nonsense mutation in LGI2 (homologue of the human epilepsy gene LGI1) in a pedigree of about 34 affected animals. The long-term follow-up by Jokinen et al. (2015) documented behavioural alterations in adults with a history of this juvenile epilepsy.

- Test breeding animals with the LGI2 test before breeding
- Avoid crossing two carriers: in ~93 % of cases the disease requires homozygosity and in ~7 % heterozygosity is enough
- A carrier can be crossed with a clear individual; test the offspring intended for breeding
- Record the history of seizures in the pedigree to guide selection
- Most puppies remit by around 4 months, but do not breed with confirmed affected animals

Differential diagnosis with neonatal hypoglycaemia, intoxications, meningoencephalitis and other epilepsies. EEG and clinical evolution guide. The course is usually benign, but not universally; some puppies require antiepileptic treatment and developmental monitoring.

1. Jokinen TS et al. 2007. Benign familial juvenile epilepsy in Lagotto Romagnolo dogs. J Vet Intern Med. PMID: 17552452
2. Seppälä EH et al. 2011. LGI2 truncation causes a remitting focal epilepsy in dogs. PLoS Genet. PMID: 21829378
3. Jokinen TS et al. 2015. Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long-Term Follow-Up Study. J Vet Intern Med. PMID: 25945683
4. Pakozdy A et al. 2015. LGI Proteins and Epilepsy in Human and Animals. J Vet Intern Med. PMID: 26032921
OMIA001596-9615.