SHANK3 and Phelan-McDermid syndrome: One such gene is SHANK3, a gene mutated in Phelan-McDermid syndrome, where primary symptoms include ASD as well as blunted pain sensitivity.78 Furthermore, in a study evaluating 201 patients with Phelan-McDermid syndrome, it was found that nearly 80% demonstrated insensitivity to pain.79 Mice lacking one or both copies of Shank3 have been shown to have an insensitivity to pain.80 Han et al.80 showed that deletion of Shank3 in peripheral sensory neurons of mice led to a decrease in inflammatory pain sensitivity.