Background The SYNGAP1 gene encodes 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. 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. 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 neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 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 trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other 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. Electronic supplementary material The online version of this article (10.1186/s11689-019-9276-y) contains supplementary material, which is available to authorized users.

Introduction: The applications of fumigation and the challenges that high-containment facilities face in achieving effective large volume decontamination are well understood. The Biosecurity Research Institute at Kansas State University sought to evaluate a novel system within their biosafety level 3 (BSL-3) and animal biosafety level 3 agriculture (ABSL-3Ag) facility. Methods: The system chosen for this study is the CURIS ® Hybrid Hydrogen Peroxide TM (HHP TM ) system, comprising a mobile 36-pound (16 kg) device delivering a proprietary 7% hydrogen peroxide (H 2 O 2 ) solution. To examine the system's efficacy in multiple laboratory settings, two BSL-3 laboratories (2,281 [65 m 3 ] and 4,668 ft 3 [132 m 3 ]) with dropped ceiling interstitial spaces and an ABSL-3Ag necropsy suite (44,212 ft 3 [1,252 m 3 ]) with 21-foot (6.4 m) ceilings were selected. Biological indicators (BIs) of Geobacillus stearothermophilus (1.7 × 10 6 organisms) on steel spore carriers and H 2 O 2 chemical indicators (CIs) were used to provide validation. Results: After cycle optimization, the smaller laboratory had a total of 60 BIs over two treatments that demonstrated a greater than 6-log reduction of bacterial spores. The larger laboratory (192 BIs) and the necropsy suite (206 BIs) had no BIs positive for spore growth when incubated at 60°C for 24 h per manufacturer's specifications. Conclusion: Overall successful results through multiple components of this study demonstrate that the HHP device, paired with the pulsed 7% H 2 O 2 solution, achieved efficacy regardless of variables in laboratory size and layout. Perceived challenges such as 21-ft (6.4 m) ceiling heights, active equipment, and difficult to access ceiling interstitial spaces proved unfounded. Given the successful sterilization of all challenged BIs, the HHP system presents a useful alternative for high level decontamination within BSL-3 and ABSL-3Ag facilities.

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