22q11.2 deletion syndrome (22q), also known as Velocardiofacial Syndrome or DiGeorge Syndrome, is one of the most common genetic syndromes with an incidence of 1 in 2500 to 1 in 4000 (Wang et al., 2009). It is the most identified human chromosomal microdeletion syndrome to date (Wang et al., 2009). 22q is associated with a wide spectrum of clinical features including various palate, cardiac, and immunological abnormalities (Lynch et al., 1995; Wang et al., 2009). 22q is also the most common genetic cause of velopharyngeal dysfunction (VPD). Posterior cranial fossa (PCF) and cervical spine variations may influence velopharyngeal (VP) port closure. Although some studies have analyzed PCF size in individuals with 22q, there has not been extensive analysis of skull base anomalies and their correlation to velopharyngeal depth. The purpose of this study was to examine PCF measures and their effects on VP dimensions in children with 22q using a non-sedated imaging protocol. 34 participants, 17 with 22q and 17 with normal VP anatomy (age range: 4-12 years) completed the study. Participants were imaged using a 3D anatomical scan. MRIs were transferred into Amira 6.4 Visualization Volume Modeling software. Linear and angular measures were obtained in the sagittal image plane on the 3D MRI scans. Measures included: distance from the palatal plane to C1, pharyngeal depth, anterior cranial base angle, posterior cranial base angle, length of the clivus, McRae line and supraocciput of the PCF, angle of clivus, and the PCF angle formed by the McRae line and the supraocciput. It is hypothesized that shorter clivus length and smaller PCF angle between McRae line and supraocciput noted in individuals with 22q DS could be related to larger pharyngeal depth, which contributes to hypernasality typically seen in 22q. Results from this study indicate that children with 22q demonstrate larger pharyngeal depth, a more obtuse anterior cranial base angle (NSB angle), a more acute posterior cranial base angle (SBO angle), shorter length of the clivus, longer supraocciput length, and a more obtuse angle of clivus. The NSB angle was positively correlated with pharyngeal depth while the SBO angle was negatively correlated with pharyngeal depth. The angle of clivus was positively correlated with both pharyngeal depth and resonance severity.