Absence Seizures in Juvenile Myoclonic Epilepsy: Whole Exome Sequencing Results and Subsyndromes (P2.008)

OBJECTIVE To refine classification of Juvenile Myoclonic Epilepsy (JME) subsyndromes in 298 cases according to age at onset of absence seizures (ABS) and results of whole exome sequencing (WES). BACKGROUND The 2011 Avignon Workshop established the diagnostic criteria for JME as onset of awakening myoclonias and EEG 4-6Hz polyspike waves between 10-25 years of age. However, ABS with/without eyelid myoclonia (EM), astatic drop, and photosensitivity confound JME nosology. DESIGN/METHODS JME cases were regrouped according to age onset of ABS: early childhood (1-5 yr) [eCA/JME], childhood (6-11y) [CA/JME], adolescence [adolABS/JME] (12-21y), and JME with ABS in adulthood (22y+). WES of 12 large JME families followed linkage and haplotype analysis. Discovered epilepsy genes were then screened in the 298 cases. RESULTS Out of 298, 134 probands (45[percnt]) had classic JME (cJME), 60 (20[percnt]) had CA/JME, 70 (23[percnt]) had adolABS/JME, 20 (7[percnt]) had eCA/JME, 9 (3[percnt]) had astatic seizures with JME, and only 5 (2[percnt]) had adulthood ABS/JME. EFHC1 variants were genetically implicated in cJME (16 cases) and CA/JME (1 case), ICK variants in cJME (7 probands) and adolABS/JME (1 proband). IPO8 variants in photosensitive CA with/without EM evolving to JME (6 probands), JME with adolABS (2 probands), JME with absence and astatic seizures (1 proband), and JME with adult onset ABS (1 proband), and 7 cases of childhood ABS only from another cohort. PROSER1 variants were implicated adolABS/JME (6 probands) and one case with cJME. MYOFERLIN variant was implicated in a proband with photosensitive eCA/ JME. CONCLUSIONS EFHC1 and ICK variants are most common in cJME, while IPO8 and MYOFERLIN variants predominate in JME with eCA, adolABS, CA/JME and adult onset ABS. PROSER1 variants associated with pyknoleptic adolABS/JME. Finding variants of genes mean JME subsyndromes are true entities and separate diseases. Study supported by NIH R01NS055057, VACO Merit Review Grant, CIDR. Disclosure: Dr. Duron has nothing to disclose. Dr. Medina has nothing to disclose. Dr. Martinez-Juarez has received personal compensation for activities with commercial entities as a consultant. Dr. Jara-Prado has nothing to disclose. Dr. Ochoa has nothing to disclose. Dr. Lopez-Ruiz has nothing to disclose. Dr. Molina has nothing to disclose. Dr. Guilhoto has nothing to disclose. Dr. Yacubian has nothing to disclose. Dr. Wight has nothing to disclose. Dr. Nguyen has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Bai has nothing to disclose. Dr. Tanaka has nothing to disclose. Dr. Patterson has nothing to disclose. Dr. Alonso has nothing to disclose. Dr. Bailey has nothing to disclose. Dr. Delgado-Escueta has nothing to disclose.