Abstracts

Rationale: Unravelling the genetics of complex disease traits increasingly occupies research groups worldwide in gathering cases and controls for genome-wide association studies (GWAS). The investigation of complex epilepsy genetics historically has lagged well behind the pack, and presents unique challenges in relation to clinical diagnostic origins, clinical heterogeneity and phenotype definition. In our study, clinicians at the coalface demonstrate that epilepsy genetics cannot be solved simply by outsourcing or by accessing established epilepsy datasets. This study not only contributes to the molecular understanding of epilepsy but also serves to highlight the crucial clinical beginnings of diagnostic clinical acumen; the centrality of clinicians in patient recruitment, motivation, and in dispelling the fear and anxiety of scientific research in epilepsy. Methods: This is an on-going gene discovery project. Families are sourced directly from physicians or clinical nurse specialists in epilepsy (CNSE), a Cardiff database of 160 registered families with epilepsy, or through self-referral methods of either responding to adverts at epilepsy research seminars or through notice boards in outpatients. The research team seeks contact directly by telephone or posts study information and decision packs. Results: Thus far 51 families have consented, had clinical data collected and DNA banked, sourced directly from physicians in 76% (39), CNSE 8% (4), 8% (4) from the Cardiff database and 8% (4) after responding to research seminars. 3 individuals without a family history of epilepsy self referred to the study through a notice board advert. Database contact has been established with families of 4 or more affected members (59), from which 8 families have been recruited, 4 of whom were already recruited by physicians, resulting in 6.8% recruitment rate from the database alone. A further 26 physician and CNSE referrals failed to respond either via a decision form or through telephone contact. From all total contacts (125), 9 declined via the decision form, 3 over the telephone and 1 contact proband had died. When reasons were given they included parental concerns, a lack of interest from one parent, lifestyle choices such as impending marriage or a wider spread familial disharmony. Some individuals declined on the basis of having achieved seizure freedom after a benign childhood epilepsy, while other reluctances were based on a previous experience where either they were subject to, or served as a witness to invasive procedures for their epilepsy in early childhood such as a lumbar puncture. Conclusions: These figures and declination statements coupled with the clinical issues inherent to the study of epilepsy genetics such as clinical heterogeneity and phenotype definition highlight a key role for clinicians at its outset. Pragmatic outcomes in epilepsy genetic research will only arise from such translational approaches of clinicians at the front door or at the coalface, alongside the technologies, health informatics and best-practice employed in the GWAS of other complex diseases states.