Abstract Details

Title Genetic Characterization and Prognosis of Adult Patients with Lennox-Gastaut Syndrome: A Prospective Case-Series Study

Topic Epilepsy/Clinical Neurophysiology (EEG)

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

Poster/Presentation
Number 6-011

Objective This study aims to analyze LGS patients for potential gene mutations contributing to the LGS phenotype, and to identify participant characteristics that may prognosticate seizure and functional outcomes in adulthood.

Background Lennox-Gastaut Syndrome (LGS) is an epileptic encephalopathy that typically presents in childhood. It is characterized by intractable seizures, including atonic or tonic seizures, intellectual disability, and interictal slow spike-and-wave complexes. Patients living with LGS are often treatment resistant and comorbid with behavioural problems. Although LGS is sometimes thought to be symptomatic to brain injury, a genetic predisposition has been proposed, but more literature is needed to establish a relationship.

Design/Methods

A chart review (2006-2017) was conducted to identify adult LGS patients who had either undergone or were candidates for genetic testing (microarray and epilepsy gene panel). Data on seizure, developmental, and intervention history was collected. Prospectively, the Vineland-3 questionnaire was administered to patients’ caregivers to evaluate the study subjects’ adaptive behaviour.

Results 23 patients were included in the study. Mean follow-up was 28 years (range 16-56 years). Mean age at follow-up was 30 years old (range 19-59 years). Mean seizure frequency at follow-up was 32 seizures/month, with 2 patients seizure free. Multinomial regression revealed that a diagnosis of ASD (χ²=10.34, p=0.016), a history of cognitive regression (χ²=11.09, p=0.011) and possessing a VUS/pathogenic mutation in a gene associated with epilepsy (χ²=9.20, p=0.027), were all predictive of worse seizure prognosis at follow-up. The Vineland-3 questionnaire showed that LGS patients are significantly delayed across all measured domains, with a relative strength in daily living skills (mean age equivalent=55 months old, range= 5-139 months) and a relative weakness in motor skills (mean age equivalent=18 months old, range= 5-71 months).

Conclusions

LGS is a complex epileptic syndrome with a poor prognosis. More research is needed to characterize long-term outcomes in adult patients and its association with genetic mutations.

Authors/Disclosures
Robert De Santis, MD (UofT Neurology) PRESENTER	No disclosure on file
	No disclosure on file
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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