Our goal is to develop quantitative endpoints for individuals with SYNGAP1-related disorder for future clinical trials of personalized therapies.

SynGAP is one of the most abundant proteins at excitatory synapses. The first individuals with germline mutations in the Synaptic Ras GTPase Activating Protein 1 (SYNGAP1) gene were described in 2009. Clinical descriptions of these patients focused on presenting symptoms of intellectual disability and epilepsy. Most existing reports rely on medical records to extract clinical characteristics but do not evaluate phenotypes in a prospective manner.

Over the past 5 years we have performed a prospective, longitudinal study of children with pathogenic SYNGAP1 mutations to gain a clearer understanding of the phenotypic spectrum and therapeutic potential for this population.  Specifically, we have collected both routine clinical and research-based data including neurophysiologic data through EEGs, brain anatomy data through MRIs, sleep data through the Children’s Sleep Habits Questionnaire as well as sleep diaries, polysomnography and actigraphy, sensory processing through the Sensory Profile 2 short form and finally developmental trajectories through the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale.

This work, for the first time, provides detailed phenotypic characterization of children with SYNGAP1-related disorder.