Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs

Jokinen, Tarja S.; Metsähonkala, Liisa; Bergamasco, L.; Viitmaa, Ranno; Syrjä, Pernilla; Lohi, Hannes; Snellman, Marjatta; Jeserevics, Janis; Cizinauskas, Sigitas

doi:10.1892/0891-6640(2007)21[464:bfjeil]2.0.co;2

Cited by 32 publications

(41 citation statements)

References 26 publications

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“…The 3 heterozygote carriers of the LGI2 mutation had had seizures similar to those in the BFJE (ie, focal‐onset seizures characterized by whole‐body tremor, ataxia, and stiffness). Clinical examinations performed on all 3 dogs excluded other seizure‐causing diseases, thus the dogs were also included in the BFJE group. In addition, a recent study has indicated that, in a minority of cases, the LGI2 mutation can cause epilepsy in the heterozygous state .…”

Section: Resultsmentioning

confidence: 99%

“…Two groups of client‐owned Lagotto Romagnolo (LR) dogs were enrolled in the study. We recruited dogs with a history of juvenile epilepsy from among dogs that had participated in a previous clinical or genetic study of BFJE by contacting the dogs' owners by email or phone and asking them to complete an online questionnaire. Those dogs the owners of which answered the online questionnaire were included in the BFJE group.…”

Section: Methodsmentioning

confidence: 99%

“…Regardless of whether childhood epilepsies are common in children, only 1 well‐defined juvenile epilepsy syndrome has been reported in dogs . Benign familial juvenile epilepsy (BFJE) in Lagotto Romagnolo dogs is characterized by focal‐onset seizures that start at the age of 5–9 weeks and spontaneously remit by the age of 13 weeks . A recent study identified a nonsense mutation in the LGI2 gene as a cause of BFJE .…”

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confidence: 99%

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Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Jokinen

Tiira

Metsähonkala

et al. 2015

Veterinary Internal Medicne

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BackgroundLagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long‐term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult‐onset epilepsies.Hypothesis/ObjectivesThe objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood.AnimalsA total of 25 LR with a history of BFJE and 91 control dogs of the same breed.MethodsOwners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog's activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case–control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy.ResultsLagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood.Conclusions and Clinical ImportanceAlthough the long‐term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Jokinen

Tiira

Metsähonkala

et al. 2015

Veterinary Internal Medicne

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“…In the Italian water dog Lagotto Romagnolo , the disease is transient, generally disappearing by 10 weeks of age, and could serve as a model for human remitting epilepsies. Analysis of a Finnish pedigree of these dogs indicated a primarily recessive inheritance (Jokinen et al, 2007). Using an expanded pedigree of these dogs, Seppälä and colleagues identified 11 pairs of discordant siblings (one affected, one not).…”

Section: The Role Of Lgi2 In Cns Developmentmentioning

confidence: 99%

LGI Proteins in the Nervous System

et al. 2013

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The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions.

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“…Childhood epilepsies are common in human medicine, and the majority of these patients will become seizure‐free by adulthood . Until now, only 1 well‐defined juvenile epilepsy syndrome was reported in dogs . BFJE in LR dogs is characterized by focal‐onset seizures beginning at a mean age of 6.3 weeks and resolving spontaneously by a mean age of 10 weeks.…”

Section: Genetic Epilepsy In Dogs Associated With Lgi Dysfunctionmentioning

confidence: 99%

LGI Proteins and Epilepsy in Human and Animals

Pákozdy

Patzl

Zimmermann

et al. 2015

Veterinary Internal Medicne

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Leucine‐rich glioma‐inactivated (LGI) protein was first thought to have a suppressor effect in the formation of some cancers. Developments in physiology and medicine made it possible to characterize the function of the LGI protein family and its crucial role in different conditions more precisely. These proteins play an important role in synaptic transmission, and dysfunction may cause hyperexcitability. Genetic mutation of LGI1was confirmed to be the cause of autosomal dominant lateral temporal lobe epilepsy in humans. The LGI2 mutation was identified in benign familial juvenile epilepsy in Lagotto Romagnolo (LR) dogs. Cats with familial spontaneous temporal lobe epilepsy have been reported, and the etiology might be associated with LGI protein family dysfunction. In addition, an autoimmune reaction against LGI1 was detected in humans and cats with limbic encephalitis. These advances prompted a review of LGI protein function and its role in different seizure disorders.

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Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs

Abstract: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Cited by 32 publications

References 26 publications

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long‐Term Follow‐Up Study

LGI Proteins in the Nervous System

LGI Proteins and Epilepsy in Human and Animals

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