Abstract Details

Title STXBP1 is associated with bruxism in awake patients

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-008

Objective We report 5 unrelated patients with de novo mutations in STXBP1 and an expanded phenotype.

Background Heterozygous mutations in STXBP1 gene are associated with early infantile epileptic encephalopathy 4 (EIEE4). This condition is characterized by epilepsy, developmental delay and various movement disorders.

Design/Methods We clinically characterized 5 patients including 3 adults with the median age of 33 years (7-46).

Results Three individuals carried missense mutation in STXBP1, while intragenic deletion and splice site deletion were identified in the other 2 patients. The patients all presented with developmental delay and refractory epilepsy. Two patients exhibited choreiform movements, and parkinsonism was identified in 2 adult patients. Three individuals demonstrated awake bruxism (a-BRX), one of them also had chorea and the other parkinsonism. The third patient with a-BRX has not developed other movement disorders. No consistent correlation was identified between the type of mutation and development of movement disorders or bruxism.

Conclusions This is the first study to demonstrate a-BRX in patients with STXBP1 mutation. Bruxism during sleep is common and not associated with pathologies. However, bruxism in awake patients is rare. It has been proposed that a-BRX is a stereotype seen in patients with significant intellectual disability (ID). However, detailed descriptions of movement disorders in patients with Lennox-Gastaut syndrome and Dravet syndrome (conditions associated with intractable epilepsy and severe ID) did not show a-BRX. Given 1) the role of STXBP1 in exocytosis of neurotransmitters, 2) other manifestations of dopamine dysregulation in STXBP1-EIEE4 patients, and 3) previous reports of a-BRX response to L-dopa (in non-STXBP1 cases), we suggest that in patients with STXBP1 a-BRX might be the result of the involvement of dopaminergic circuits. Further studies of the function of STXBP1, analysis of larger samples of STXBP1 patients and a-BRX response to L-dopa are required to better determine the pathophysiology of movement disorders seen in these patients.

Authors/Disclosures
PRESENTER	No disclosure on file
Victor Lira, MD (University Health Network)	No disclosure on file
	No disclosure on file
Shelly K. Weiss, MD (HSC)	No disclosure on file
Elizabeth Donner, MD, FRCPC (The Hospital for Sick Children)	Dr. Donner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Donner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Donner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pendopharm. Dr. Donner has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Seizure. The institution of Dr. Donner has received research support from SickKids Centre for Brain and Mental Health. The institution of Dr. Donner has received research support from Ontario Brain Institute. The institution of Dr. Donner has received research support from CIHR.
Maria M. Zak, NP (The Hospital for Sick Children Dept. of Neurology)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
O. C. Snead III, MD, FAAN (Hospital for Sick Children)	Dr. Snead has nothing to disclose.
Alfonso Fasano, MD, PhD, FAAN (Toronto Western Hospital - U of Toronto)	Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Medtronic. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceregate. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Inbrain Neuroelectronics. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos Health. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annovis. Dr. Fasano has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CADTH. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for International Parkinson and Movement Disorders Society. The institution of Dr. Fasano has received research support from Boston Scientific. The institution of Dr. Fasano has received research support from Medtronic. The institution of Dr. Fasano has received research support from Abbvie. The institution of Dr. Fasano has received research support from Canadian Institutes of Health Research (CIHR). The institution of Dr. Fasano has received research support from Michael J Fox Foundation. The institution of Dr. Fasano has received research support from Bluerock Therapeutics. Dr. Fasano has received publishing royalties from a publication relating to health care. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with CenteR for Advancing Neurological Innovation to Application (CRANIA) that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with HopeNET that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Medical Advisory Committee with International Essential Tremor Foundation that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Member with Tremor Research Group that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Co-Chair with Tremor Study Group of the IPMDS that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Vice-Chair with NPH Study Group of the IPMDS that is relevant to AAN interests or activities. Dr. Fasano has a non-compensated relationship as a Vice-Chair with Industry Committee of the IPMDS that is relevant to AAN interests or activities.
Danielle M. Andrade, MD (University of Toronto)	The institution of Dr. Andrade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Andrade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceutical. The institution of Dr. Andrade has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke Therapeutics. The institution of Dr. Andrade has received research support from Epilepsy Canada. The institution of Dr. Andrade has received research support from SynGAP Research Fund. Dr. Andrade has received publishing royalties from a publication relating to health care. Dr. Andrade has a non-compensated relationship as a Former Chair of task force on Transition with International League Against Epilepsy that is relevant to AAN interests or activities. Dr. Andrade has a non-compensated relationship as a President with Canadian League Against Epilepsy that is relevant to AAN interests or activities.

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