Background: The Belgian shepherd Groenendael and Tervueren is believed to be at higher risk of developing epilepsy than dogs of the common population. This epidemiological study was designed to estimate the prevalence of epilepsy in the Danish population of Groenendael and Tervueren born between 1995 and 2004. Furthermore, it was the intention to describe the clinical manifestation (seizure types and phenomenology) of epilepsy and to identify risk factors for euthanasia once the dog was diagnosed as having epilepsy.
Epilepsy is the most common neurological disorder in dogs, with an incidence ranging from 0.5% to up to 20% in particular breeds. Canine epilepsy can be etiologically defined as idiopathic or symptomatic. Epileptic seizures may be classified as focal with or without secondary generalization, or as primary generalized. Nine genes have been identified for symptomatic (storage diseases) and one for idiopathic epilepsy in different breeds. However, the genetic background of common canine epilepsies remains unknown. We have studied the clinical and genetic background of epilepsy in Belgian Shepherds. We collected 159 cases and 148 controls and confirmed the presence of epilepsy through epilepsy questionnaires and clinical examinations. The MRI was normal while interictal EEG revealed abnormalities and variable foci in the clinically examined affected dogs. A genome-wide association study using Affymetrix 50K SNP arrays in 40 cases and 44 controls mapped the epilepsy locus on CFA37, which was replicated in an independent cohort (81 cases and 88 controls; combined p = 9.70×10−10, OR = 3.3). Fine mapping study defined a ∼1 Mb region including 12 genes of which none are known epilepsy genes or encode ion channels. Exonic sequencing was performed for two candidate genes, KLF7 and ADAM23. No variation was found in KLF7 but a highly-associated non-synonymous variant, G1203A (R387H) was present in the ADAM23 gene (p = 3.7×10−8, OR = 3.9 for homozygosity). Homozygosity for a two-SNP haplotype within the ADAM23 gene conferred the highest risk for epilepsy (p = 6.28×10−11, OR = 7.4). ADAM23 interacts with known epilepsy proteins LGI1 and LGI2. However, our data suggests that the ADAM23 variant is a polymorphism and we have initiated a targeted re-sequencing study across the locus to identify the causative mutation. It would establish the affected breed as a novel therapeutic model, help to develop a DNA test for breeding purposes and introduce a novel candidate gene for human idiopathic epilepsies.
This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have a strong resemblance to what has been reported for familial partial (focal) epilepsy in humans with variable foci with suggestion of linkage to chromosome 2 and chromosome 22q12.
Background: Epilepsy with a genetic background is increasingly being identified. In certain dog breeds, epilepsy occurs with a higher prevalence than the estimate of 1-2% reported in the general dog population.Hypothesis: The Petit Basset Griffon Vendeen (PBGV) experiences an increased occurrence of epilepsy compared to the general dog population.Animals: The target population consisted of all 876 PBGV dogs registered in the Danish Kennel Club from January 1, 1999 to December 31, 2008. The study population included 820 dogs that met the inclusion criteria.Methods: A population study was conducted to estimate the prevalence of epilepsy in the Danish PBGV population. A mailed questionnaire was used to detect possible signs of epilepsy. The information was subsequently validated by telephone interviews of positive and possible positive responders and a negative responder control group, using an extensive questionnaire developed to detect epilepsy. Dogs evaluated as epilepsy positive after the telephone interview were offered a clinical investigation.Results: The prevalence of epilepsy was estimated to be 8.9% (42/471) in the PBGV population. Average age of onset was 26.3 months. Sex and mode of response did not affect the prevalence, but a strong litter effect was seen. Among euthanized dogs, epilepsy was the predominant cause (6/45 = 13.3%).Conclusion and Clinical Importance: Petit Basset Griffon Vendeen dogs experience an increased risk of epilepsy characterized by a relatively early onset and dominated by focal seizures with and without secondary generalization. With an estimated prevalence of 8.9% and substantial clustering within litters, a genetic factor associated with epilepsy is suspected.
Background: Belgian Shepherds have focal genetic epilepsy. The prevalence of epilepsy has been estimated as 9.5% in the breed and as 33% in the family investigated. Dogs with epilepsy might have an increased risk of premature death.Objective/Hypothesis: To investigate survival and selected risk factors for premature death in a Belgian Shepherd family with genetic epilepsy.Animals: One hundred ninety-nine related Belgian Shepherds. Methods: Longitudinal observational study, 2009-2011. Follow-up telephone interviews were all conducted using a structured questionnaire addressing epilepsy, including seizure history and phenomenology, possible remission, possible death, and cause of death.Results: The life span of epileptic dogs was not significantly shortened by the presence of epilepsy (P = .87). Epilepsy was the predominant cause of death in the population (19/75 = 25%) and epilepsy-related deaths accounted for 70% (19/ 27) of all deaths in the group of dogs with epilepsy. Two probable sudden unexpected deaths related to epilepsy occurred in dogs with generalized seizures. Cluster seizures occurred in 33% (17/51) but did not significantly influence the life span of epileptic dogs. Dogs with epilepsy had an epilepsy remission proportion of 13.7%.Conclusion and Clinical Importance: The Belgian Shepherds investigated in the present study display a focal genetic epilepsy with an overall benign course. The life span was not significantly affected by the presence of epilepsy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.