Abstract Details

Title Phenotypic Characterization of Individuals with SYNGAP1 Pathogenic Variants Reveals Correlation Between Posterior Dominant Rhythm and Developmental Progression

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-033

Objective The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression

Background The SYNGAP1 gene encondes for a small GTPase regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy.

Design/Methods A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included: genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging and serial neurodevelopmenta/behavioral assessments. All patients were seen longitudinally between July 2012 and May 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed.

Results Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism Spectrum Disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a moderate positive correlation between visual-perceptual/fine motor/adaptive skills (R²=0.58), and language development (R²=0.56), with posterior dominant rhythm on EEG, independent of age. No other significant neurophysiology-development associations or correlations were identified.

Conclusions A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker.

Authors/Disclosures
Andres Jimenez Gomez, MD PRESENTER	Dr. Jimenez Gomez has nothing to disclose.
	No disclosure on file
	No disclosure on file
Elizabeth McQuade, MD (WVU Health Sciences Center, Ruby Memorial Hosptial)	Dr. McQuade has nothing to disclose.
Alfred Balasa, MD	Dr. Balasa has nothing to disclose.
David Huss, MD (Baylor College of Medicine/Texas Children'S Hospital)	No disclosure on file
Rohini Coorg, MD (Baylor College of Medicine/Texas Children'S Hospital)	Dr. Coorg has nothing to disclose.
Michael Quach, MD	No disclosure on file
	No disclosure on file
Sarah R. Risen, MD	Dr. Risen has nothing to disclose.
Jimmy Holder, MD (BCM)	Dr. Holder has received personal compensation in the range of $0-$499 for serving as a Consultant with Stoke Pharmaceutical.

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