Sensory Reactivity Phenotype in Phelan-McDermid Syndrome Is Distinct from Idiopathic ASD

Phelan-McDermid syndrome (PMS) is one of the most common genetic forms of autism spectrum disorder (ASD). While sensory reactivity symptoms are widely reported in idiopathic ASD (iASD), few studies have examined sensory symptoms in PMS. The current study delineates the sensory reactivity phenotype and examines genotype-phenotype interactions in a large sample of children with PMS. Sensory reactivity was measured in a group of 52 children with PMS, 132 children with iASD, and 54 typically developing (TD) children using the Sensory Assessment for Neurodevelopmental Disorders (SAND). The SAND is a clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on the DSM-5 criteria for ASD. Children with PMS demonstrated significantly greater hyporeactivity symptoms and fewer hyperreactivity and seeking symptoms compared to children with iASD and TD controls. There were no differences between those with Class I deletions or sequence variants and those with larger Class II deletions, suggesting that haploinsufficiency of SHANK3 is the main driver of the sensory phenotype seen in PMS. The syndrome-specific sensory phenotype identified in this study is distinct from other monogenic forms of ASD and offers insight into the potential role of SHANK3 deficiency in sensory reactivity. Understanding sensory reactivity abnormalities in PMS, in the context of known glutamatergic dysregulation, may inform future clinical trials in the syndrome.

Automated summary

Phelan-McDermid syndrome (PMS) is a common genetic form of autism spectrum disorder (ASD), with children showing significantly greater hyporeactivity symptoms and fewer hyperreactivity and seeking symptoms compared to children with idiopathic ASD (iASD) and typically developing (TD) children. The study suggests that haploinsufficiency of SHANK3 is the main driver of the sensory phenotype seen in PMS, and the sensory abnormalities identified in PMS may inform future clinical trials in the syndrome.