Abstracts

Rationale: The three most common childhood epilepsies are Rolandic (RE), Childhood Absence (CAE) and Juvenile Myoclonic (JME) Epilepsy, accounting for 15, 10-15 and 5-10% of cases respectively {Berg 2013, Avanzini 2009, Panayiotopoulos 2010, Camfield 2013}. There is abundant evidence that genetic factors play important roles in each of these conditions though none (in the vast majority of families) is inherited in Mendelian fashion and all are therefore genetically complex {Andermann & Metrakos 1969, Tsuboi 1973, Valdamudi et al 2006, Delgado-Escueta 2007, Panayiotopoulos 2010}. Only a few genes have been associated with these very common diseases, and then only in a small minority of patients. Metrakos and Metrakos reported that approximately 50% of clinically unaffected, age-matched first degree relatives of patients with centrencephalic epilepsy had the same age-dependent generalized EEG abnormalities as the latter, and suggested that while the epilepsy itself was not inherited in Mendelian fashion, the EEG trait, present as it is in nearly 50% of young adolescent relatives, may well be {Metrakos and Metrakos 1961}. A decade following the Metrakos' work, studies in RE also reported a rate of EEG abnormality in clinically unaffected siblings of approximately 50% when the siblings were studied during the range of childhood years in which RE occurs {Bray 1964, Heijbel et al 1975, Degen & Degen 1990, Degen & Degen 1992}. RE, CAE and JME are not only common, they also are 'pure' epilepsies in which the CNS is otherwise grossly morphologically and functionally intact. As such, understanding the pathogeneses of these benign conditions will be highly insightful to the overall understanding of epilepsy. Solving the genetic complexities of RE, CAE and JME would be greatly aided were any aspect of these conditions, e.g. their specific EEG traits, inherited in simpler, perhaps Mendelian, fashion. Given the opaqueness of and contradictions in the literature regarding the frequencies of EEG abnormalities in unaffected relatives of patients with RE, CAE and JME, we decided to perform a meta-analysis of this literature and clarify the current state of knowledge. Methods: MEDLINE, EMBASE, CINHAL and Cochrane databases were searched. Two independent reviewers conducted all screening levels, data abstraction, and quality appraisal. A meta-analysis was performed. Results: After screening 10,233 citations and 210 full-text articles, 14 studies were included. A total 3799 asymptomatic relatives were included. The prevalence of all abnormal waves in asymptomatic relatives was 31%. Prevalence for each epilepsy type was 21% for JME, 42% for CAE and 33% for RE. Conclusions: Prevalence of abnormal EEG waves of asymptomatic relatives of our included idiopathic epilepsies was 31% and 41%. Further studies are needed and further analysis is required to confirm these results in order to know the mode of inheritance in asymptomatic relatives of JME, CAE and RE. Looking at each epilepsy type individually, prevalence of these abnormal EEG waves in asymptomatic relatives of JME, RE and CAE patients were 21%, 33% and 42% respectively from our meta-analysis. We caution that the reliability and utility of our findings is somewhat limited by the quality of individual studies. The results of our review suggest that in the non-epileptic relatives of JME, CAE and RE tend to follow a Mendelian type of inheritance. However, it is necessary to conduct further studies and further analysis to confirm our results. The next steps should be for investigators to test inheritance patters or identify major genes. Funding: No funding