This case report describes the successful use of low dose quetiapine in the treatment of agitation in a patient with Treacher–Collins syndrome (TCS) and suspected autistic spectrum disorder (ASD). Results from this case report found better efficacy in controlling symptoms of agitation in ASD utilizing lower doses of quetiapine. TCS is a genetic disorder that is characterized by a mandibulofacial dysostosis but is not associated with developmental delay, nor is it associated with a high risk of co-morbid autism, and to our knowledge, there are no previous reports of a co-occurrence of TCS and ASD in the extant literature. There are reports of mandibulofacial dysostosis associated with co-morbid developmental delay that are similar but distinct from TCS, however these reports do not comment on the treatment of agitation in this patient population. The results described in this case report demonstrate a reduction of agitation with low dose quetiapine, and offers support for the reconceptualization of agitation in ASD as a primary affective dysregulation which is also in line with evidence from the extant literature regarding the neurobiologic basis of aggression.