The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders in humans. There is an increased risk of Parkinson’s disease (PD) in individuals with 22q11DS. The characteristic motor features of PD begin when more than 50% of dopaminergic neurons in the substantia nigra have degenerated. Before this, there is a prodromal period, of up to 20 years, in which nonmotor features such as hyposmia, autonomic dysfunction, rapid eye movement sleep behavior disorder, and subtle motor dysfunction can occur. We used validated clinical tools to investigate the presence of prodromal markers of PD in 50 adults with 22q11DS and 14 matched deletion-negative controls. The median score on the University of Pennsylvania Smell Identification Test was significantly lower in the 22q11 deletion group, and 44% scored in the hyposmic range (P=0.024). Individuals with 22q11DS were significantly more likely to report autonomic symptoms (urinary dysfunction or constipation, P=0.016). Twenty-eight percent of 22q11DS participants scored above the threshold for rapid eye movement sleep behavior disorder on a screening questionnaire (P=0.022). Four 22q11DS participants had parkinsonian motor signs on examination, which did not fulfill the diagnostic criteria for PD. We report prodromal markers of PD in 22q11DS. These may help identify individuals with 22q11 deletion at risk of neurological disease. However, the significance of these signs needs to be confirmed by longitudinal studies of development of PD.