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.

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.