Abstracts

Rationale: Complex multigenic factors appear to play an important role in the development of idiopathic generalized epilepsy (IGE) and non-symptomatic localization-related epilepsy (LRE), and in the pharmacoresponsiveness or pharmacoresistance of such patients to antiepileptic drugs. De novo genomic mutations may cause cryptogenic forms of infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), and certain malformations of cortical development (MCD). Progress in understanding the complex genetic and developmental mechanisms contributing to these forms of epilepsy will require an elaborate analysis of phenotypic and genotypic data from a large number of subjects. The Epilepsy Phenome/Genome Project (EPGP) was initiated in May 2007 to accomplish this goal. Methods: EPGP is a network of 14 academic institutions and NINDS. The organizational structure includes an Administrative Core, Phenomics Core, Imaging Core, Electrophysiology Core, Pharmacogenomics Core, Genomics Core, Data Analysis Core, and Informatics Core. 13 epilepsy centers constitute the current EPGP Clinical Centers that identify and enroll subjects. The first part of the project seeks to enroll: 1,500 sibling pairs with IGE or LRE (750 probands with IGE and 750 probands with LRE); 1,500 matched controls; 250 IS patients and their parents; 250 LGS patients and their parents; 250 MCD patients (specifically, polymicrogyria or periventricular nodular heterotopia) and their parents (total of 6,750 subjects). Detailed phenotypic information is collected via structured interviews, medical record abstraction, and collection of brain magnetic resonance imaging and electrophysiological studies. De-identified data are entered locally via an integrated, HIPAA and FISMA compliant, web-based informatics platform, and then sent in encrypted form to a secure EPGP Data Repository. Encoded and de-identified whole blood samples are collected from all subjects and deposited in the NINDS Human Genetics DNA and Cell Line Repository. The study timeline has 4 phases: finalization of instruments and establishment of administrative, informatics, and scientific cores; 6-month pilot study of the scientific instruments and workflow; expansion to 9 additional clinical centers; devising of the genomics analyses. Results: The administrative structure and cores have been established as planned, and more than 90% of the informatics infrastructure for all facets of the workflow has been completed. To date, 4 EPGP Clinical Centers have been enrolling subjects for 5 months, and the remaining 9 sites are in the process of initiating enrollment. As of May 31, 2008, 782 individuals have been screened at the 4 initial sites and 158 subjects have been enrolled. Conclusions: EPGP is now actively enrolling subjects from throughout the U.S. The project will create a highly detailed phenotypic database coupled to a permanent repository of DNA and cell lines, and will thus constitute a national resource for the study of the genetic basis of specific types of epilepsy. (Supported by NINDS U01 NS053998)