Objectives: The 22q11.2 microdeletion syndrome is the most common human microdeletion syndrome. Neuropsychiatric (NP) manifestations in this genetic syndrome are not uncommon, but not well-understood and associated with unfavorable outcome. We reviewed the NP manifestations in children with 22q11.2 microdeletion syndrome and tried to identify the associated clinical variables.Methods: We retrospectively analyzed the medical records of 145 patients (72 males) genetically diagnosed with 22q11.2 microdeletion syndrome at Asan Medical Center Children’s Hospital between March 1996 and June 2013. Clinical data included NP and other clinical symptoms, neuroradiologic and electrophysiologic findings, treatments and outcomes. Results: Among 145 patients with 22q11.2 microdeletion syndrome, 78 (53.8%) developed NP manifestations, most commonly with developmental delay/cognitive impairment (n=71), epilepsy (n=22), and psychiatric illness (n=16). Neuroradologic studies revealed malformation of cortical development in 6, agenesis of corpus callosum in 1, hypoplasia of cerebral artery in 1, and Chiari malformation in 1. In 22 patients with epilepsy, the mean age of epilepsy onset was 3.3 (0-17) years and 9 patients were diagnosed as idiopathic epilepsy including one with juvenile myoclonic epilepsy. Regarding psychiatric illnesses, attention-deficit hyperactivity disorder were identified in 10, mood disorder in 5, and schizophrenia in 3. Clinical variables including prematurity and congenital heart disease were not associated with the development of NP manifestations in this genetic syndrome. Conclusion: Patients carrying the 22q11.2 microdeletion syndrome are at risk for diverse NP manifestations across the life span. Therefore, diagnostic screening and early proper management for NP manifestation should be considered in these patients.