Phelan-McDermid Syndrome (PMS) results from a deletion within the 22q13 chromosome region. Most children have specific physical morphology and developmental delays with many displaying characteristics of autism spectrum disorder (ASD) including abnormalities in social development. The behavioral aspect of PMS that parallels ASD has raised particular interest as the SHANK3 gene, which lies in the 22q13 region, is important for synaptic development, and animal SHANK3 knockout models demonstrate ASD characteristics thereby confirming the importance of this gene in PMS. However, despite the importance of the SHANK3 gene, individuals with PMS have variations in their development, behavior and medical characteristics that cannot be fully explained by the SHANK3 deletion.