22q11.2 deletion syndrome (22q11DS), also known as velo-cardio-facial syndrome (VCFS) is the most common copy number variant (CNV) in humans caused by a microdeletion on chromosome 22q11.2. The phenotype encompasses heart anomalies, cleft palate and cognitive difficulties. Alongside brain differences in VCFS, such as reduced hippocampal volume, different cognitive developmental trajectories can be observed. The aim of this study was to explore the developmental trajectories of cognitive inhibition in memory using longitudinal data acquired in a large cohort of individuals with 22q11DS and the brain correlates to those developmental changes. 51 participants with 22q11DS (mean age: 13.75 ± 4.26, mean IQ score: 70.50 ± 10.75) and 43 typically developing individuals matched for age (M = 13.50 ± 4.91) and gender were recruited. To explore inhibition in memory, the Directed Forgetting paradigm was used. 30 words were presented, half were 'To be remembered items'(TBR) and the other half 'To be forgotten items' (TBF). To measure source memory, participants were asked during the recognition stage to say if the world was a TBR or a TBF item. Participants were tested during two consecutive visits, with a mean interval of 3 years. T1-weighted images were acquired using a 1.5 T Philips or a 3 T Siemens scanner at both visits. Both groups recognized more TBR than TBF items (Directed forgetting effect), however, participants with 22q11DS recognized fewer TBR items and did not show an increased recognition of TBR items with age. Furthermore, in participants with VCFS increased source memory errors with age was associated with a decline in hippocampal volume.