The clinical and genetic epidemiology of pediatric idiopathic epilepsy in Newfoundland and Labrador

• Main Author: Mahoney, Krista
• Format: Thesis
• Language: English
• Published: Memorial University of Newfoundland 2014
• Subjects: Newfoundland
• Online Access: https://research.library.mun.ca/8173/; https://research.library.mun.ca/8173/1/thesis.pdf

Background: Epilepsy is a common and very heterogeneous neurologic disorder which shows a predilection towards the pediatric population. Idiopathic epilepsy (IE) refers to cases with no known underlying etiology other than a presumed genetic predisposition. IE accounts for approximately half of all cases of epilepsy. Newfoundland and Labrador has a tertiary referral center for pediatric neurology patients where virtually all children living on the Avalon Peninsula are treated. The current study aims to determine the clinical and genetic epidemiologic characteristics in this population. Purpose: To describe the incidence, genetic and clinical epidemiology of pediatric IE in the province of Newfoundland and Labrador. Methods: All children < 15 years of age with IE were ascertained through the provincial pediatric neurology clinic at the Janeway Child Health Centre. Family history, medical history and blood samples were obtained from affected children and their family members. All blood samples were screened for mutations in the seven candidate genes (SCN1A, SCN2A, SCN1B, KCNQ2, GABRA1, GABRG2 and KCNQ3) of highest priority, based on previously reported phenotype-genotype relationships, by direct bidirectional Sanger DNA sequencing. Results: The mean annual incidence of IE for the population of children living on the Avalon region of Newfoundland from 2000 to 2004 was 107 per 100 000. This rate is approximately three-fold greater than comparable populations in other developed countries. Incidence was similar in males and females. Multiple different epilepsy phenotypes were identified between and amongst families. Of 117 families with IE eligible for study, 86 (74%) provided detailed pedigree data. Fifty-five families (64%) had a positive family history. Eight (9%) of these had family histories compatible with autosomal dominant (AD) inheritance and these families lived in five different geographic isolates. DNA was obtained from 79 individuals in 21 families. Seven genes previously associated with childhood ...