Search Results (4)

SYNGAP1-related disorder is a rare neurodevelopmental disorder characterized by intellectual and motor disabilities, including disordered gait control. Currently, there have been few studies that have assessed the gait of individuals with SYNGAP1-related disorder using technology-based collection techniques. The purpose of this investigation was to characterize the kinematic gait pattern of these individuals using camera-based motion capture technology during treadmill walking. Both linear and non-linear analysis techniques were used to analyze bilateral lower-limb joint motion and compare the results to age-matched neurotypical individuals. Results indicate that joint range of motion and velocity were decreased in the patient population relative to the neurotypical participants with the non-linear measures of angle–angle and phase portrait areas reflecting similar outcomes. The combination of linear and non-linear measures provide complementary information that, when used in combination, can provide deeper insights into the coordination and control of gait than if either of the measurement techniques are used in isolation. Such information can be useful to clinicians and therapists to develop targeted interventions designed to improve the gait of individuals with SYNGAP1-related disorder. Full article

Background: The human brain relies on complex synaptic communication regulated by key genes such as SYNGAP1. SYNGAP1 encodes the GTPase-Activating Protein (SYNGAP), a critical synaptic plasticity and neuronal excitability regulator. Impaired SYNGAP1 function leads to neurodevelopmental disorders (NDDs) characterized by intellectual disability (ID), epilepsy, and behavioral abnormalities. These variants disrupt Ras signaling, altering AMPA receptor transport and synaptic plasticity and contributing to cognitive and motor difficulties. Despite advancements, challenges remain in defining genotype–phenotype correlations and distinguishing SYNGAP1-related disorders from other NDDs, which could improve underdiagnosis and misdiagnosis. Brain Gene Registry: The Brain Gene Registry (BGR) was established as a collaborative initiative, consolidating genomic and phenotypic data across multiple research centers. This database allows for extensive analyses, facilitating improved diagnostic accuracy, earlier interventions, and targeted therapeutic strategies. The BGR enhances our understanding of rare genetic conditions and is critical for advancing research on SYNGAP1-related disorders. Conclusions: While no FDA-approved treatments exist for SYNGAP1-related disorders, several therapeutic approaches are being investigated. These include taurine supplementation, ketogenic diets, and molecular strategies such as antisense oligonucleotide therapy to restore SYNGAP1 expression. Behavioral and rehabilitative interventions remain key for managing developmental and cognitive symptoms. Advancing research through initiatives like the BGR is crucial for refining genotype–phenotype associations and developing precision medicine approaches. A comprehensive understanding of SYNGAP1-related disorders will improve clinical outcomes and patient care, underscoring the need for continued interdisciplinary collaboration in neurodevelopmental genetics. Full article

Sensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASDs). Significant work has been carried out to characterize and classify specific sensory profiles in non-syndromic autism. However, it is not known if syndromic autism disorders, such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID), have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding their underlying mechanisms. Our objective in this work was to determine the sensory processing abnormalities present in two syndromic ASDs: Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability. Using a standardized instrument, the Short Sensory Profile-2, we characterized sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID, and sub-scores were then calculated for seeking, avoiding, sensitivity and registration, as well as overall sensory and behavior scores. We found both patient groups exhibited atypical sensory features, including high scores in the areas of avoiding and seeking. Thus, we discovered significant sensory processing abnormalities are common in these syndromic ASDs. Measurements of sensory processing could serve as useful clinical endpoints for trials of novel therapeutics for these populations. Full article

Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at the synapse. Mutations in these genes cause derangement of synapse development and function. We utilized a validated sleep instrument, Children’s Sleep Habits Questionnaire (CSHQ) to examine the nature of sleep abnormalities occurring in individuals with two synaptopathies—Phelan–McDermid syndrome (PMD) (N = 47, male = 23, female = 24, age 1–46 years) and SYNGAP1-related intellectual disability (SYNGAP1-ID) (N = 64, male = 31, female = 33, age 1–64 years), when compared with unaffected siblings (N = 61, male = 25, female = 36, age 1–17 years). We found that both PMD and SYNGAP1-ID have significant sleep abnormalities with SYNGAP1-ID having greater severity of sleep disturbance than PMD. In addition, sleep disturbances were more severe for PMD in individuals 11 years and older compared with those less than 11 years old. Individuals with either disorder were more likely to use sleep aids than unaffected siblings. In conclusion, sleep disturbances are a significant phenotype in the synaptopathies PMD and SYNGAP1-ID. Improved sleep is a viable endpoint for future clinical trials for these neurodevelopmental disorders. Full article