Abstracts

Rationale: The seizures associated with Benign Epilepsy with Centrotemporal Spikes (BECTS) have characteristic semiology often allowing clinical diagnosis by description of the events alone. We describe a case of BECTS initially presenting as a familial kinesiogenic movement disorder prior to progression to more typical seizures, and evaluation of this unique presentation with whole exome sequencing.Methods: We review the clinical history and EEG data of an unsual case of BECTS presenting with familial kinesiogenic movement disorder. We hypothesized an autosomal dominant mode of transmission. Whole exome sequencing was performed on the proband and both parents, as well as an unaffected sibling to identify possible causative genes for this unique presentation of a common epilepsy syndrome. Results: We describe a healthy 5yo boy who presented with intermittent non-suppressible myoclonic jerks of his right arm and leg, which were associated with active movement of the limb or with intention to move, lasting throughout the action and persisting several minutes into rest. An EEG confirmed the presence of left greater than right centrotemporal spikes with clinical correlation of these EEG findings with myoclonic arm movements. There was an increased frequency of centrotemporal discharges with action or intention to move. Several months after onset of these movements the patient presented with nocturnal focal seizure events characteristic of BECTS. Family history revealed a similar childhood history of jerking movements precipitated by action in the patient s father. Whole exome sequencing identified 13 candidate genetic variants in developmentally regulated, CNS-expressed genes which were shared by the proband and his father, including ULK1, NBEAL1, SESN1, SNX13, BRSK2 and AVIL. No polymorphisms or mutations were identified in this family in known genes or loci associated with BECTS such as CHRNA7, KCNQ2 or GRIN2A, suggesting that these candidate genes represent novel potential causes of this common epilepsy syndrome. Confirmatory studies are ongoing. Conclusions: This case describes an unusual presentation of BECTS as a paroxysmal movement disorder with autosomal dominant inheritance. The epileptic nature of these movements was confirmed by EEG. Whole exome sequencing suggests new candidate genes for this unique presentation of this common disorder.