The disorder is caused by heterozygous de novo variants in the ARF1 gene. The identified variants include missense mutations, a frameshift mutation predicted to cause nonsense-mediated decay, and a splice altering variant resulting in an in-frame insertion. Functional studies on several missense variants have demonstrated a significant decrease in ARF1 activity. ARF1 encodes a small GTPase involved in vesicle trafficking and cell adhesion molecule turnover. The suspected pathophysiologic mechanism is likely related to reduced ARF1 function affecting neuronal migration and other cellular processes. Diagnostic testing involves genetic sequencing of the ARF1 gene.
ARF1